IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent IMFINZI as adjuvant treatment following RC

EFFICACY

In the treatment of cis-eligible MIBC

What were the event-free survival results demonstrated in the NIAGARA study?

PERIOPERATIVE IMFINZI* + neoadjuvant gem-cis: The FIRST FDA-approved IO-based regimen to significantly improve EFS compared with neoadjuvant gem-cis in patients with MIBC1,2†

EVENT-FREE SURVIVAL (dual primary endpoint)1,3

NIAGARA Study Results Showing a 32% Reduction in Event Risk with the NIAGARA Regimen Versus Neoadjuvant Gemcitabine Plus Cisplatin.

REDUCTION IN RISK OF AN EVENT (progression, recurrence, death, or not undergoing RC)† with the NIAGARA Regimen‡ vs neoadjuvant gem-cis (HR=0.68 [95% CI, 0.56-0.82]; P<0.0001)

Median EFS was not reached with the NIAGARA Regimen‡ (95% CI, NR-NR) vs 46.1 months with neoadjuvant gem-cis (95% CI, 32.2-NR)

Median duration of follow-up: 42.3 months (range: 0.03-61.3).

EVENT-FREE SURVIVAL (dual primary endpoint)1,3

NIAGARA Study EFS Graph Showing Higher 12- and 24- Month Event-Free Survival with the NIAGARA Regimen Versus Neoadjuvant Gemcitabine Plus Cisplatin.
NIAGARA Study EFS Graph Showing Higher 12- and 24- Month Event-Free Survival with the NIAGARA Regimen Versus Neoadjuvant Gemcitabine Plus Cisplatin.
 

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  • Approximately 68% of patients treated with the NIAGARA Regimen‡ were estimated to be event free at 2 years3
  • EFS rates at 12 and 24 months were not powered to determine statistical significance3
  • EFS maturity is 39%3

What were the EFS results across patient subgroups?

In the NIAGARA study, EFS data were consistent across most prespecified patient subgroups3

EFS BY PRESPECIFIED PATIENT SUBGROUP (exploratory analysis)1,3

NIAGARA Study Forest Plot Showing EFS Across Prespecified Patient Subgroups.
NIAGARA Study Forest Plot Showing EFS Across Prespecified Patient Subgroups.
 

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The EFS prespecified patient subgroup analysis was not powered to show differences between or within individual subgroups and was not powered to determine statistical significance.3

*A perioperative regimen consists of both neoadjuvant and adjuvant treatment.1

†Event-free survival was defined as the time from randomization to first recurrence of disease post-RC, time to first documented progression in patients who were precluded from RC, time of expected surgery in patients who refused RC or failure to undergo RC due to residual disease, or death due to any cause, whichever occurs first.3

‡The NIAGARA Regimen is defined as neoadjuvant IMFINZI + gem-cis followed by adjuvant IMFINZI as a single agent after RC.1

pCR RESULTS (dual primary endpoint): PRIMARY ANALYSIS AND EXPLORATORY REANALYSIS3

  • At the primary analysis (data cutoff: January 2022), 33.8% (n=180/533; 95% CI, 29.8-38.0) of patients treated with the NIAGARA Regimen‡ and 25.8% (n=137/530; 95% CI, 22.2-29.8) of patients treated with neoadjuvant gem-cis achieved a pCR
    • pCR rates reported during the primary analysis did not reach statistical significance
  • At the reanalysis (data cutoff: April 2024), 37.3% (n=199/533; 95% CI, 33.2-41.6) of patients treated with the NIAGARA Regimen‡ and 27.5% (n=146/530; 95% CI, 23.8-31.6) of patients treated with neoadjuvant gem-cis achieved a pCR
    • The reanalysis included an additional 59 patients§
    • This analysis was exploratory and not powered to determine statistical significance

§The descriptive reanalysis of pCR included the results of 59 evaluable samples that were omitted from the primary analysis because the date of central assessment (which occurred after January 14, 2022), rather than the date of surgery (which occurred before January 14, 2022), was used as the data cutoff date.

NCCN

CATEGORY 1,

PREFERRED

The first and only NCCN Category 1, Preferred perioperative systemic treatment option for cis-eligible MIBC

Neoadjuvant durvalumab (IMFINZI®) + gemcitabine + cisplatin, followed by cystectomy, then adjuvant durvalumab (IMFINZI®) for cis-eligible MIBC4||

Neoadjuvant durvalumab (IMFINZI®) + gemcitabine + cisplatin, followed by cystectomy, then adjuvant durvalumab (IMFINZI®) for cis-eligible MIBC4||

||See the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for detailed recommendations, including other preferred treatment options.4

NCCN=National Comprehensive Cancer Network® (NCCN®).

In the treatment of cis-eligible MIBC

What were the overall survival results demonstrated in the NIAGARA study?

PERIOPERATIVE IMFINZI* + neoadjuvant gem-cis: The FIRST FDA-approved IO-based regimen to achieve superior improvement in OS compared with neoadjuvant gem-cis alone in the curative intent setting of MIBC1,2

OVERALL SURVIVAL (secondary endpoint)1,3

NIAGARA Study Results Showing a 25% Reduction in Risk of Death with the NIAGARA Regimen Versus Neoadjuvant Gemcitabine Plus Cisplatin.

REDUCTION IN RISK OF DEATH with the NIAGARA Regimen† vs neoadjuvant gem-cis (HR=0.75 [95% CI, 0.59-0.93]; P=0.01)

Median OS was not reached with the NIAGARA Regimen† (95% CI, NR-NR) nor with neoadjuvant gem-cis (95% CI, NR-NR)

Fewer deaths were reported with the NIAGARA Regimen† (25.5%; n=136/533) vs neoadjuvant gem-cis (31.9%, n=169/530)1,3

Median duration of follow-up: 46.3 months (range: 0.03-64.7).
The key secondary endpoint was OS as assessed with an alpha-allocation approach, following EFS in the statistical hierarchy.

OVERALL SURVIVAL (secondary endpoint)1,3

NIAGARA Study OS Graph Showing Higher 12- and 24- Month Overall Survival with the NIAGARA Regimen.
NIAGARA Study OS Graph Showing Higher 12- and 24- Month Overall Survival with the NIAGARA Regimen.
 

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>82% estimated OS rate at 2 years with the NIAGARA Regimen3†

  • OS rates at 12 and 24 months were not powered to determine statistical significance3
  • OS maturity is 27%3

What were the OS results across patient subgroups?

In the NIAGARA study, OS data were consistent across most prespecified patient subgroups3

OS BY PRESPECIFIED PATIENT SUBGROUP ANALYSIS (exploratory analysis)1,3

Niagara Study Exploratory Analysis of OS Across Prespecified Patient Subgroups.
Niagara Study Exploratory Analysis of OS Across Prespecified Patient Subgroups.
Overall Survival by Prespecified Patient Subgroup
 

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The OS prespecified patient subgroup analysis was not powered to show differences between or within individual subgroups and was not powered for statistical significance.3

Hear what experts say about the NIAGARA Regimen†

Dr Neal Shore and Dr Aleksandra Drakaki discuss their experience with the NIAGARA Regimen†

*A perioperative regimen consists of both neoadjuvant and adjuvant treatment.1

†The NIAGARA Regimen is defined as neoadjuvant IMFINZI + gem-cis followed by adjuvant IMFINZI as a single agent after RC.1

What were the EFS and OS results by pCR status in the NIAGARA study?

EFS* results by pCR status

EFS RESULTS IN PATIENTS WITH AND WITHOUT A pCR (post-hoc analysis)5

NIAGARA Study Post-Hoc Analysis of Event-Free Survival by Pathologic Complete Response Status, Based on an Exploratory pCR Reanalysis.
NIAGARA Study Post-Hoc Analysis of Event-Free Survival by Pathologic Complete Response Status, Based on an Exploratory pCR Reanalysis.
 

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  • For this analysis, pCR status was based on the exploratory reanalysis of pCR3,5‡
  • Post-hoc analysis of EFS by pCR status was not powered to determine statistical significance5
  • Data cutoff was April 29, 20245

OS results by pCR status

OS RESULTS IN PATIENTS WITH AND WITHOUT A pCR (post-hoc analysis)5

NIAGARA Study OS Analysis Demonstrating Favorable Survival Trends Across pCR and Non-pCR Subgroups.
NIAGARA Study OS Analysis Demonstrating Favorable Survival Trends Across pCR and Non-pCR Subgroups.
 

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OS in Patients With and Without a pCR
  • For this analysis, pCR status was based on the exploratory reanalysis of pCR3,5‡
  • Post-hoc analysis of OS by pCR status was not powered to determine statistical significance5
  • Data cutoff was April 29, 20245

What were the baseline characteristics in the subgroups of patients with and without a pCR?

Baseline characteristics were generally well balanced between treatment arms in the subgroups of patients with and without a pCR5

BASELINE CHARACTERISTICS IN PATIENTS WITH AND WITHOUT A pCR (post-hoc analysis)1,3,5

Baseline Characteristics of NIAGARA Study Patients by pCR Outcome and Treatment Group.
Baseline Characteristics of NIAGARA Study Patients by pCR Outcome and Treatment Group.
Overall Survival by Prespecified Patient Subgroup
 

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*Event-free survival was defined as the time from randomization to first recurrence of disease post-RC, time to first documented progression in patients who were precluded from RC, time of expected surgery in patients who refused RC or failure to undergo RC due to residual disease, or death due to any cause, whichever occurs first.3

†The NIAGARA Regimen is defined as neoadjuvant IMFINZI + gem-cis followed by adjuvant IMFINZI as a single agent after RC.1

‡At the reanalysis (data cutoff: April 2024), 37.3% (n=199/533; 95% CI, 33.2-41.6) of patients treated with the NIAGARA Regimen† and 27.5% (n=146/530; 95% CI, 23.8-31.6) of patients treated with neoadjuvant gem-cis achieved a pCR.3

§Assessed with the VENTANA PD-L1 (SP263) Assay using the TC/IC25% algorithm. High PD-L1 expression was defined as ≥25% of TCs with any membrane staining, or ICs staining for PD-L1 at any intensity.5

Surgical Data

What were the surgical data in the NIAGARA study?

Time to RC following neoadjuvant treatment was similar between treatment arms: 39 days (range: 8-118) with IMFINZI + gem-cis and 38 days (range: 12-333) with gem-cis3

PERCENTAGE OF PATIENTS WHO UNDERWENT RC1,3

88% of Patients in the IMFINZI Plus Gem-Cis Arm Underwent Radical Cystectomy (RC).
83% of Patients in the Gem-Cis Arm Underwent Radical Cystectomy (RC).

REASONS FOR NOT UNDERGOING OR COMPLETING RC3

  The NIAGARA Regimen*
(n=533)		 Neoadjuvant gem-cis
(n=530)
Patients who did not undergo surgery–no.(%) 63 (11.8%) 84 (15.8%)
Patient decision 6% 6.8%
Unfit for surgery 0.4% 1.1%
Adverse event† 1.1% 1.3%
Disease progression 1.7% 1.7%
Death 0.9% 1.5%
Study discontinuation 0.6% 2.3%
Investigator decision 0.9% 1.1%
Abandoned surgery (intra-operative) 0.2% 0%

Patient decision was the primary reason for not undergoing RC

 

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The percentage of patients with an adverse reaction‡ that prevented RC was
the same across both treatment arms (0.2%)1

  • 1 patient experienced interstitial lung disease leading to cancellation of surgery in the IMFINZI + gem-cis arm1
  • 1.7% (n=9) of patients in the IMFINZI + gem-cis arm and 1.1% (n=6) of patients in the gem-cis arm experienced a surgical delay§ due to AEs3

*The NIAGARA Regimen is defined as neoadjuvant IMFINZI + gem-cis followed by adjuvant IMFINZI as a single agent after RC.1

†Adverse event: Any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related.6

‡Adverse reaction: Any adverse event caused by a drug. Adverse reactions are a subset of all suspected adverse reactions where there is a reason to conclude that the drug caused the event.6

§Defined as occurring more than 56 days after the last dose of neoadjuvant treatment.1

Study Design

What was the NIAGARA study design?

NIAGARA was the largest Phase III study in cis-eligible MIBC, with >1000 patients1,2

The FIRST FDA-APPROVED regimen to combine perioperative IO* with neoadjuvant gem-cis for the treatment of cis-eligible MIBC1,2

  • The NIAGARA study evaluated a broad population of patients. Patients with borderline renal function (CrCl ≥40 mL/min to <60 mL/min) received split-dose cisplatin1,3†

NIAGARA STUDY DESIGN: PHASE III, MULTICENTER, OPEN-LABEL STUDY1,3

NIAGARA Phase III Trial Design Comparing Neoadjuvant and Adjuvant IMFINZI Plus Gem-Cis with Standard Gem-Cis Treatment.

Key inclusion criteria

  • Cis-eligible resectable MIBC (T2-T4aN0/1M0) with transitional cell and mixed transitional cell histology
  • Planning to undergo RC
  • No prior systemic chemotherapy or IO for NMIBC or MIBC
  • ECOG PS 0 or 1
  • Life expectancy ≥12 weeks at randomization
  • CrCl of ≥40 mL/min
  • Any PD-L1 expression

Stratification factors

  • Clinical tumor stage (T2N0 vs >T2N0)
  • PD-L1 status (high vs low/negative expression)
  • Renal function (borderline [CrCl ≥40 mL/min to <60 mL/min] vs adequate [≥60 mL/min])
NIAGARA Phase III Trial Design Comparing Neoadjuvant and Adjuvant IMFINZI Plus Gem-Cis with Standard Gem-Cis Treatment.

Key exclusion criteria1:

  • Pure non-urothelial or any small cell histology
  • Primary non-bladder cancer of the urothelium

Dual primary endpoints (ITT)3:

  • Event-free survival (EFS) by BICR§||
  • Pathological complete response (pCR) rates by blinded central pathology review

Select secondary endpoints1,3:

  • Overall survival (OS)
  • Proportion of patients who underwent RC
  • Safety and tolerability

What were the baseline characteristics of the patient population studied in the NIAGARA study?

The NIAGARA study included a broad population of patients including those with variant histologies, borderline renal function, and PD-L1 low/negative expression1,3

BASELINE CHARACTERISTICS (ITT)3

Baseline characteristics The NIAGARA Regimen
(n=533)		 Neoadjuvant gem-cis
(n=530)
Median age (range), years 65 (34-84) 66 (32-83)
Sex (male) 82% 82%
Race#
White
Asian
Black/other
Missing data
66%
29%
2%
3%
68%
27%
1%
4%
Region — no. (%)
Europe
Asia
North American and Australia
South America
50%
28%
12%
10%
54%
27%
12%
7%
ECOG PS score**
0
1
78%
22%
78%
22%
Current/former smoker 71% 75%
Histology type††
Urothelial carcinoma
Urothelial carcinoma with variant histology		 86%
14%		 83%
17%
Tumor stage††‡‡
T2N0
>T2N0
40%
60%
40%
60%
Regional lymph nodes††
N0
N1
95%
5%
94%
6%
PD-L1 expression§§
High (≥25% of tumor cells)
Low/negative
73%
27%
73%
27%
Renal function
Adequate (CrCl ≥60 mL/min)
Borderline (CrCl ≥40 to <60 mL/min)
81%
19%
81%
19%

~1 out of  7 patients treated with the NIAGARA Regimen* had UC with variant histology

19% of patients
treated with the NIAGARA Regimen* had borderline renal function (CrCl ≥40 to
<60 mL/min)

27% of patients treated with the NIAGARA Regimen* had PD-L1 low/negative expression

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#Race was reported by the patient.

**ECOG PS scores range from 0 to 5, with higher scores indicating greater disability.

††Histologic type, tumor stage, and regional lymph-node stage were assessed by the investigator on the basis of a pathological tumor assessment of a sample obtained during transurethral resection of the bladder tumor, an examination of the patient under anesthesia after the transurethral resection of the bladder tumor, and findings on computed tomography or magnetic resonance imaging.

‡‡Tumor staging was performed according to the eighth edition of the American Joint Committee on Cancer AJCC Cancer Staging Manual.

§§Baseline samples were assessed with the Ventana PD-L1 (SP263) assay (Ventana Medical Systems) according to the TC/IC25% algorithm, in which a high expression level was defined as PD-L1 expression on at least 25% of tumor cells, at least 25% of immune cells if immune cells were present in more than 1% of the tumor area, or 100% of immune cells if immune cells were present in 1% of the tumor area.

Baseline disease characteristics were well balanced across treatment arms3

*A perioperative regimen consists of both neoadjuvant and adjuvant treatment.1

†Patients with borderline renal function (CrCl ≥ 40mL/min to <60 mL/min) received split-dose cisplatin (35 mg/m2 on Days 1 and 8 of each cycle).1,3

‡Day 1: Cisplatin 70 mg/m2, gemcitabine 1000 mg/m2; Day 8: Gemcitabine 1000 mg/m2; every 21 days for 4 cycles.1,3

§Or by CPR if a biopsy was needed for analysis of a suspected new lesion.3

||Event-free survival was defined as the time from randomization to first recurrence of disease post-RC, time to first documented progression in patients who were precluded from RC, time of expected surgery in patients who refused RC or failure to undergo RC due to residual disease, or death due to any cause, whichever occurs first.3

The NIAGARA Regimen is defined as neoadjuvant IMFINZI + gem-cis followed by adjuvant IMFINZI as a single agent after RC.1

KEY POINTS: Efficacy

The NIAGARA Regimen* significantly improved EFS and OS compared with neoadjuvant gem-cis in patients with MIBC

  • 32% REDUCTION IN RISK OF AN EVENT (progression, recurrence, death, or not undergoing RC)† with the NIAGARA Regimen* vs neoadjuvant gem-cis (HR=0.68 [95% CI, 0.56-0.82]; P<0.0001)1,3
    • Median EFS was not reached with the NIAGARA Regimen* (95% CI, NR-NR) vs 46.1 months with neoadjuvant gem-cis (95% CI, 32.2-NR)1,3
  • 25% REDUCTION IN RISK OF DEATH with the NIAGARA Regimen* vs neoadjuvant gem-cis (HR=0.75 [95% CI, 0.59-0.93]; P=0.01)1,3
    • Median OS was not reached with the NIAGARA Regimen* (95% CI, NR-NR) nor with neoadjuvant gem-cis (95% CI, NR-NR)1,3
  • The NIAGARA Regimen* was studied across a broad population of cis-eligible MIBC patients, including those with PD-L1 low/negative status, borderline renal function (CrCl ≥40 mL/min to <60 mL/min), and N1 involvement1,3
*

The NIAGARA Regimen is defined as neoadjuvant IMFINZI + gem-cis followed by adjuvant IMFINZI as a single agent after RC.1

†

Event-free survival was defined as the time from randomization to first recurrence of disease post-RC, time to first documented progression in patients who were precluded from RC, time of expected surgery in patients who refused RC or failure to undergo RC due to residual disease, or death due to any cause, whichever occurs first.3

View efficacy data
HOME SAFETY
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SEE FULL INDICATIONS

IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.

IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).

IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).

IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR).

IMPORTANT SAFETY INFORMATION

There are no contraindications for IMFINZI® (durvalumab) or IMJUDO® (tremelimumab-actl).

Severe and Fatal Immune-Mediated
Adverse Reactions

Indications:

IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy.

IMFINZI is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not

IMPORTANT SAFETY INFORMATION

There are no contraindications for IMFINZI® (durvalumab) or IMJUDO® (tremelimumab-actl).

Severe and Fatal Immune-Mediated
Adverse Reactions

Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated reactions. Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment or after discontinuation. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate clinical chemistries including liver enzymes, creatinine, adrenocorticotropic hormone (ACTH) level, and thyroid function at baseline and before each dose. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate. Withhold or permanently discontinue IMFINZI and IMJUDO depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI and IMJUDO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroid therapy.

Indications:

IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).

IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.

IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).

IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).

IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).

IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-authorized test.

IMFINZI in combination with Bacillus Calmette-Guérin (BCG) is indicated for the treatment of adult patients with BCG-naive, high-risk non-muscle-invasive bladder cancer (HR-NMIBC).

IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle-invasive bladder cancer (MIBC).

IMFINZI in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) as neoadjuvant and adjuvant treatment, followed by single agent IMFINZI, is indicated for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).

Immune-Mediated Pneumonitis

IMFINZI and IMJUDO can cause immune-mediated pneumonitis, which may be fatal. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

  • IMFINZI as a Single Agent
    • In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions.
    • In patients who received recent prior radiation, the incidence of pneumonitis (including radiation pneumonitis) in patients with unresectable Stage III NSCLC following definitive chemoradiation within 42 days prior to initiation of IMFINZI in PACIFIC was 18.3% (87/475) in patients receiving IMFINZI and 12.8% (30/234) in patients receiving placebo. Of the patients who received IMFINZI (475), 1.1% were fatal and 2.7% were Grade 3 adverse reactions.
    • The incidence of pneumonitis (including radiation pneumonitis) in patients with LS-SCLC following chemoradiation within 42 days prior to initiation of IMFINZI in ADRIATIC was 14% (37/262) in patients receiving IMFINZI and 6% (16/265) in patients receiving placebo. Of the patients who received IMFINZI (262), 0.4% had a fatal adverse reaction and 2.7% had Grade 3 adverse reactions.
    • The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy.
  • IMFINZI with IMJUDO
    • Immune-mediated pneumonitis occurred in 1.3% (5/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.3%) and Grade 3 (0.2%) adverse reactions.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated pneumonitis occurred in 3.5% (21/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.5%), and Grade 3 (1%) adverse reactions.

Immune-Mediated Colitis

IMFINZI with IMJUDO and platinum-based chemotherapy can cause immune-mediated colitis, which may be fatal. IMFINZI and IMJUDO can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

  • IMFINZI as a Single Agent
    • Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.
  • IMFINZI with IMJUDO
    • Immune-mediated colitis or diarrhea occurred in 6% (23/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (3.6%) adverse reactions. Intestinal perforation has been observed in other studies of IMFINZI and IMJUDO.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated colitis occurred in 6.5% (39/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including fatal (0.2%) and Grade 3 (2.5%) adverse reactions. Intestinal perforation and large intestine perforation were reported in 0.1% of patients.

Immune-Mediated Hepatitis

IMFINZI and IMJUDO can cause immune-mediated hepatitis, which may be fatal.

  • IMFINZI as a Single Agent
    • Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions.
  • IMFINZI with IMJUDO
    • Immune-mediated hepatitis occurred in 7.5% (29/388) of patients receiving IMFINZI and IMJUDO, including fatal (0.8%), Grade 4 (0.3%) and Grade 3 (4.1%) adverse reactions.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated hepatitis occurred in 3.9% (23/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including fatal (0.3%), Grade 4 (0.5%), and Grade 3 (2%) adverse reactions.

Immune-Mediated Endocrinopathies

  • Adrenal Insufficiency: IMFINZI and IMJUDO can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated.
    • IMFINZI as a Single Agent
      • Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
    • IMFINZI with IMJUDO
      • Immune-mediated adrenal insufficiency occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions.
    • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
      • Immune-mediated adrenal insufficiency occurred in 2.2% (13/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.8%) adverse reactions.
  • Hypophysitis: IMFINZI and IMJUDO can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated.
    • IMFINZI as a Single Agent
      • Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI.
    • IMFINZI with IMJUDO
      • Immune-mediated hypophysitis/hypopituitarism occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO.
    • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
      • Immune-mediated hypophysitis occurred in 1.3% (8/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions.
  • Thyroid Disorders: IMFINZI and IMJUDO can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.
    • IMFINZI as a Single Agent
      • Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
      • Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI.
      • Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
    • IMFINZI with IMJUDO
      • Immune-mediated thyroiditis occurred in 1.5% (6/388) of patients receiving IMFINZI and IMJUDO.
      • Immune-mediated hyperthyroidism occurred in 4.6% (18/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.3%) adverse reactions.
      • Immune-mediated hypothyroidism occurred in 11% (42/388) of patients receiving IMFINZI and IMJUDO.
    • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
      • Immune-mediated thyroiditis occurred in 1.2% (7/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy.
      • Immune-mediated hyperthyroidism occurred in 5% (30/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions.
      • Immune-mediated hypothyroidism occurred in 8.6% (51/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.5%) adverse reactions.
    • IMFINZI with Carboplatin and Paclitaxel
      • Immune-mediated hypothyroidism occurred in 14% (34/235) of patients receiving IMFINZI in combination with carboplatin and paclitaxel.
  • Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated.
    • IMFINZI as a Single Agent
      • Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI.
    • IMFINZI with IMJUDO
      • Two patients (0.5%, 2/388) had events of hyperglycemia requiring insulin therapy that had not resolved at last follow-up.
    • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
      • Immune-mediated Type 1 diabetes mellitus occurred in 0.5% (3/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy including Grade 3 (0.3%) adverse reactions.

Immune-Mediated Nephritis with Renal Dysfunction

IMFINZI and IMJUDO can cause immune-mediated nephritis.

  • IMFINZI as a Single Agent
    • Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
  • IMFINZI with IMJUDO
    • Immune-mediated nephritis occurred in 1% (4/388) of patients receiving IMFINZI and IMJUDO, including Grade 3 (0.5%) adverse reactions.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated nephritis occurred in 0.7% (4/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.2%) adverse reactions.

Immune-Mediated Dermatology Reactions

IMFINZI and IMJUDO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes.

  • IMFINZI as a Single Agent
    • Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) adverse reactions.
  • IMFINZI with IMJUDO
    • Immune-mediated rash or dermatitis occurred in 4.9% (19/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Immune-mediated rash or dermatitis occurred in 7.2% (43/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions.

Immune-Mediated Pancreatitis

IMFINZI in combination with IMJUDO can cause immune-mediated pancreatitis. Immune-mediated pancreatitis occurred in 2.3% (9/388) of patients receiving IMFINZI and IMJUDO, including Grade 4 (0.3%) and Grade 3 (1.5%) adverse reactions.

Other Immune-Mediated Adverse Reactions

The following clinically significant, immune-mediated adverse reactions occurred at an incidence of less than 1% each in patients who received IMFINZI and IMJUDO or were reported with the use of other immune-checkpoint inhibitors.

  • Cardiac/vascular: Myocarditis, pericarditis, vasculitis.
  • Nervous system: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.
  • Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment to include blindness can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.
  • Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.
  • Musculoskeletal and connective tissue disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatica.
  • Endocrine: Hypoparathyroidism.
  • Hematologic/Immune: Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.
  • Other: Myocarditis-Myositis-Myasthenia Gravis (or Myasthenia-Like) Overlap Syndrome, reported as the co-occurrence of either two or all three adverse reactions.

Infusion-Related Reactions

IMFINZI and IMJUDO can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI and IMJUDO based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses.

  • IMFINZI as a Single Agent
    • Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.
  • IMFINZI with IMJUDO
    • Infusion-related reactions occurred in 2.6% (10/388) of patients receiving IMFINZI and IMJUDO.
  • IMFINZI with IMJUDO and Platinum-Based Chemotherapy
    • Infusion-related reactions occurred in 2.9% (17/596) of patients receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy, including Grade 3 (0.3%) adverse reactions.

Complications of Allogeneic HSCT after IMFINZI

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/L-1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on their mechanism of action and data from animal studies, IMFINZI and IMJUDO can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and IMJUDO and advise them to use effective contraception during treatment with IMFINZI and IMJUDO and for 3 months after the last dose of IMFINZI and IMJUDO.

Lactation

There is no information regarding the presence of IMFINZI and IMJUDO in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI and IMJUDO, advise women not to breastfeed during treatment and for 3 months after the last dose.

Adverse Reactions

Unresectable Stage III NSCLC

  • In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), the most common adverse reactions (≥20%) were cough (40%), fatigue (34%), pneumonitis or radiation pneumonitis (34%), upper respiratory tract infections (26%), dyspnea (25%), and rash (23%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonia (7%) and pneumonitis/radiation pneumonitis (3.4%).
  • In patients with Stage III NSCLC in the PACIFIC study receiving IMFINZI (n=475), discontinuation due to adverse reactions occurred in 15% of patients in the IMFINZI arm. Serious adverse reactions occurred in 29% of patients receiving IMFINZI. The most frequent serious adverse reactions (≥2%) were pneumonitis or radiation pneumonitis (7%) and pneumonia (6%). Fatal pneumonitis or radiation pneumonitis and fatal pneumonia occurred in <2% of patients and were similar across arms.

Resectable NSCLC

  • In patients with resectable NSCLC in the AEGEAN study, the most common adverse reactions (occurring in ≥20% of patients) were anemia, nausea, constipation, fatigue, musculoskeletal pain, and rash.
  • In patients with resectable NSCLC in the neoadjuvant phase of the AEGEAN study receiving IMFINZI in combination with platinum-containing chemotherapy (n=401), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 6.7% of patients. Serious adverse reactions occurred in 21% of patients. The most frequent (≥1%) serious adverse reactions were pneumonia (2.7%), anemia (1.5%), myelosuppression (1.5%), vomiting (1.2%), neutropenia (1%), and acute kidney injury (1%). Fatal adverse reactions occurred in 2% of patients, including death due to COVID-19 pneumonia (0.5%), sepsis (0.5%), myocarditis (0.2%), decreased appetite (0.2%), hemoptysis (0.2%), and death not otherwise specified (0.2%). Of the 401 IMFINZI-treated patients who received neoadjuvant treatment and 398 placebo-treated patients who received neoadjuvant treatment, 1.7% (n=7) and 1% (n=4), respectively, did not receive surgery due to adverse reactions.
  • In patients with resectable NSCLC in the adjuvant phase of the AEGEAN study receiving IMFINZI as a single agent (n=265), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 8% of patients. Serious adverse reactions occurred in 13% of patients. The most frequent serious adverse reactions reported in >1% of patients were pneumonia (1.9%), pneumonitis (1.1%), and COVID-19 (1.1%). Four fatal adverse reactions occurred during the adjuvant phase of the study, including COVID-19 pneumonia, pneumonia aspiration, interstitial lung disease and aortic aneurysm.

Metastatic NSCLC

  • In patients with mNSCLC in the POSEIDON study receiving IMFINZI and IMJUDO plus platinum-based chemotherapy (n=330), the most common adverse reactions (occurring in ≥20% of patients) were nausea (42%), fatigue (36%), musculoskeletal pain (29%), decreased appetite (28%), rash (27%), and diarrhea (22%).
  • In patients with mNSCLC in the POSEIDON study receiving IMFINZI in combination with IMJUDO and platinum-based chemotherapy (n=330), permanent discontinuation of IMFINZI or IMJUDO due to an adverse reaction occurred in 17% of patients. Serious adverse reactions occurred in 44% of patients, with the most frequent serious adverse reactions reported in at least 2% of patients being pneumonia (11%), anemia (5%), diarrhea (2.4%), thrombocytopenia (2.4%), pyrexia (2.4%), and febrile neutropenia (2.1%). Fatal adverse reactions occurred in a total of 4.2% of patients.

Limited-stage Small Cell Lung Cancer

  • In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), the most common adverse reactions occurring in ≥20% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (38%), and fatigue (21%). The most common Grade 3 or 4 adverse reactions (≥3%) were pneumonitis or radiation pneumonitis and pneumonia.
  • In patients with limited-stage SCLC in the ADRIATIC study receiving IMFINZI (n=262), IMFINZI was permanently discontinued due to adverse reactions in 16% of the patients receiving IMFINZI. Serious adverse reactions occurred in 30% of patients receiving IMFINZI. The most frequent serious adverse reactions reported in ≥1% of patients receiving IMFINZI were pneumonitis or radiation pneumonitis (12%), and pneumonia (5%). Fatal adverse reactions occurred in 2.7% of patients who received IMFINZI including pneumonia (1.5%), cardiac failure, encephalopathy and pneumonitis (0.4% each).

Extensive-stage Small Cell Lung Cancer

  • In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), the most common adverse reactions (≥20%) were nausea (34%), fatigue/asthenia (32%), and alopecia (31%). The most common Grade 3 or 4 adverse reaction (≥3%) was fatigue/asthenia (3.4%).
  • In patients with extensive-stage SCLC in the CASPIAN study receiving IMFINZI plus chemotherapy (n=265), IMFINZI was discontinued due to adverse reactions in 7% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 31% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 1% of patients were febrile neutropenia (4.5%), pneumonia (2.3%), anemia (1.9%), pancytopenia (1.5%), pneumonitis (1.1%), and COPD (1.1%). Fatal adverse reactions occurred in 4.9% of patients receiving IMFINZI plus chemotherapy.

Locally Advanced or Metastatic Biliary Tract Cancers (BTCs)

  • In patients with locally advanced or metastatic BTCs in the TOPAZ-1 study receiving IMFINZI (n=338), the most common adverse reactions (occurring in ≥20% of patients) were fatigue (42%), nausea (40%), constipation (32%), decreased appetite (26%), abdominal pain (24%), rash (23%), and pyrexia (20%).
  • In patients with locally advanced or metastatic BTCs in the TOPAZ-1 study receiving IMFINZI (n=338), discontinuation due to adverse reactions occurred in 6% of the patients receiving IMFINZI plus chemotherapy. Serious adverse reactions occurred in 47% of patients receiving IMFINZI plus chemotherapy. The most frequent serious adverse reactions reported in at least 2% of patients were cholangitis (7%), pyrexia (3.8%), anemia (3.6%), sepsis (3.3%), and acute kidney injury (2.4%). Fatal adverse reactions occurred in 3.6% of patients receiving IMFINZI plus chemotherapy. These include ischemic or hemorrhagic stroke (4 patients), sepsis (2 patients), and upper gastrointestinal hemorrhage (2 patients).

Unresectable Hepatocellular Carcinoma (HCC)

  • In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), the most common adverse reactions (occurring in ≥20% of patients) were rash (32%), diarrhea (27%), fatigue (26%), pruritus (23%), musculoskeletal pain (22%), and abdominal pain (20%).
  • In patients with unresectable HCC in the HIMALAYA study receiving IMFINZI and IMJUDO (n=388), serious adverse reactions occurred in 41% of patients. Serious adverse reactions in >1% of patients included hemorrhage (6%), diarrhea (4%), sepsis (2.1%), pneumonia (2.1%), rash (1.5%), vomiting (1.3%), acute kidney injury (1.3%), and anemia (1.3%). Fatal adverse reactions occurred in 8% of patients who received IMFINZI and IMJUDO, including death (1%), hemorrhage intracranial (0.5%), cardiac arrest (0.5%), pneumonitis (0.5%), hepatic failure (0.5%), and immune-mediated hepatitis (0.5%). Permanent discontinuation of treatment regimen due to an adverse reaction occurred in 14% of patients.

Primary Advanced or Recurrent dMMR Endometrial Cancer

  • In patients with primary advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent (n=44), the most common adverse reactions, including laboratory abnormalities (occurring in ≥20% of patients) were peripheral neuropathy (61%), musculoskeletal pain (59%), nausea (59%), alopecia (52%), fatigue (41%), abdominal pain (39%), constipation (39%), rash (39%), decreased magnesium (36%), increased ALT (32%), increased AST (30%), diarrhea (27%), vomiting (27%), cough (27%), decreased potassium (25%), dyspnea (25%), headache (23%), increased alkaline phosphatase (20%), and decreased appetite (18%). The most common Grade 3 or 4 adverse reactions (≥3%) were constipation (4.5%) and fatigue (4.5%).
  • In patients with primary advanced or recurrent dMMR endometrial cancer in the DUO-E study receiving IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent (n=44), permanent discontinuation of IMFINZI due to adverse reactions occurred in 11% of patients. Serious adverse reactions occurred in 30% of patients who received IMFINZI with carboplatin and paclitaxel; the most common serious adverse reactions (≥4%) were constipation (4.5%) and rash (4.5%).

BCG-Naive, High-Risk Non-Muscle-Invasive Bladder Cancer (HR-NMIBC)

  • In patients with BCG-naive, HR-NMIBC in the POTOMAC study receiving IMFINZI in combination with BCG, the most common (≥20%) adverse reactions, including laboratory abnormalities were increased glucose (43%), increased AST (43%), increased lipase (42%), increased ALT (42%), increased GGT (40%), urinary tract infection (40%), increased potassium (39%), dysuria (37%), decreased hemoglobin (35%), hematuria (33%), increased serum creatinine (30%), musculoskeletal pain (28%), decreased lymphocytes (27%), urinary frequency (26%), decreased sodium (23%), fatigue (21%), rash (20%), and pyrexia (20%).
  • In patients with BCG-naive, HR-NMIBC in the POTOMAC study receiving IMFINZI in combination with BCG, permanent discontinuation of IMFINZI due to adverse reactions occurred in 18% of patients. The adverse reactions which resulted in permanent discontinuation of IMFINZI (≥1%) were hepatitis (1.8%), acute kidney injury (1.2%), and diarrhea (1.2%). Serious adverse reactions occurred in 32% of patients. The most common (≥1%) serious adverse reactions were urinary tract infection (4.5%), COVID (1.8%), hepatitis (1.5%), dysuria (1.2%), and prostate cancer (1.2%). Fatal adverse reactions occurred in 2.4% of patients who received IMFINZI in combination with BCG, including congestive cardiac failure (0.6%), COVID (0.3%), cardiovascular disorder (0.3%), dementia with Lewy bodies (0.3%), and pancreatic cancer (0.3%).

Muscle-Invasive Bladder Cancer (MIBC)

  • In patients with MIBC, the most common adverse reactions, including laboratory abnormalities, in the overall study (occurring in ≥20% of patients) were decreased hemoglobin, decreased neutrophils, increased blood creatinine, decreased sodium, nausea, increased ALT, decreased calcium, decreased platelets, fatigue, increased potassium, decreased lymphocytes, increased AST, constipation, decreased magnesium, decreased appetite, increased alkaline phosphatase, rash, pyrexia, diarrhea, vomiting and abdominal pain.
  • In patients with MIBC in the neoadjuvant phase of the NIAGARA study receiving IMFINZI in combination with gemcitabine and cisplatin (n=530), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 9% of patients. Serious adverse reactions occurred in 24% of patients; the most frequent (≥1%) serious adverse reactions were pulmonary embolism (1.9%), febrile neutropenia (1.5%), acute kidney injury (1.3%), thrombocytopenia (1.3%), urinary tract infection (1.3%), and pneumonia (1.3%). Fatal adverse reactions occurred in 1.1% of patients including sepsis, myocardial infarction, and pulmonary embolism (0.2% each). One fatal adverse reaction of pneumonia was reported in 1 (0.2%) patient in the post-surgery phase before adjuvant treatment started. Of the 530 patients in the IMFINZI treatment arm and 526 patients in the chemotherapy treatment arm who received neoadjuvant treatment, 1 (0.2%) patient in each treatment arm did not receive surgery due to adverse reactions. The adverse reaction that led to cancellation of surgery in the IMFINZI treatment arm was interstitial lung disease.
  • In patients with MIBC in the adjuvant phase of the NIAGARA study receiving IMFINZI as a single agent (n=383), permanent discontinuation of adjuvant IMFINZI due to an adverse reaction occurred in 5% of patients. Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions (occurring in ≥1% of patients) were urinary tract infection (7%), acute kidney injury (3.7%), hydronephrosis (2.1%), pyelonephritis (2.1%), urosepsis (1.8%) and sepsis (1.6%). Fatal adverse reactions occurred in 1.8% of patients, including COVID-19, severe acute respiratory syndrome, cardiopulmonary failure, gastrointestinal hemorrhage, and chronic hepatic failure (0.3% each).

Resectable Gastric Cancer/Gastroesophageal Junction Adenocarcinoma (GC/GEJC)

  • In patients with resectable GC/GEJC, the most common adverse reactions in the overall study (occurring in ≥20% of patients) were diarrhea, nausea, peripheral neuropathy, fatigue, alopecia, decreased appetite, rash, abdominal pain, vomiting, musculoskeletal pain, pyrexia, and stomatitis.
  • In patients with resectable GC/GEJC in the neoadjuvant phase of the MATTERHORN study receiving IMFINZI in combination with FLOT chemotherapy (n=475), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 2.5% of patients. Serious adverse reactions occurred in 21% of patients; the most frequent (≥2%) serious adverse reaction was diarrhea (2.5%). Deaths occurred in 1.9% of patients; deaths of ≥2 patients included septic shock (0.6%) and acute coronary syndrome (0.4%). Of the 475 patients in the IMFINZI + FLOT chemotherapy treatment arm and 469 patients in the placebo + FLOT chemotherapy treatment arm who received neoadjuvant treatment, 0.6% and 0.4% of patients, respectively, did not receive surgery due to adverse reactions, and 2.3% and 2.6% of patients, respectively, had a delay in surgery due to ARs.
  • In patients with resectable GC/GEJC in the adjuvant phase of the MATTERHORN study receiving IMFINZI in combination with FLOT chemotherapy (n=365), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 7% of patients. Serious adverse reactions occurred in 29% of patients; the most frequent (≥2%) serious adverse reaction was pneumonia (2.5%). Deaths occurred in 2.2% of patients; deaths of ≥2 patients included gastrointestinal perforation (0.5%) and COVID-19 (0.5%).
  • In patients with resectable GC/GEJC in the adjuvant phase of the MATTERHORN study receiving IMFINZI alone (n=345), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 6% of patients. Serious adverse reactions occurred in 14% of patients. Deaths occurred in 1.7% of patients; deaths of ≥2 patients included gastrointestinal perforation (0.6%) and COVID-19 (0.6%).

The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients.

Please see Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO.

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The safety and effectiveness of IMFINZI and IMJUDO have not been established in pediatric patients.

Indications:

IMFINZI, as a single agent, is indicated for the treatment of adult patients with unresectable Stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).

IMFINZI in combination with platinum-containing chemotherapy as neoadjuvant treatment, followed by IMFINZI continued as a single agent as adjuvant treatment after surgery, is indicated for the treatment of adult patients with resectable (tumors ≥4 cm and/or node positive) NSCLC and no known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.

IMFINZI, in combination with IMJUDO and platinum-based chemotherapy, is indicated for the treatment of adult patients with metastatic NSCLC with no sensitizing EGFR mutations or ALK genomic tumor aberrations.

IMFINZI, as a single agent, is indicated for the treatment of adult patients with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy (cCRT).

IMFINZI, in combination with etoposide and either carboplatin or cisplatin, is indicated for the first-line treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC).

IMFINZI, in combination with gemcitabine and cisplatin, is indicated for the treatment of adult patients with locally advanced or metastatic biliary tract cancer (BTC).

IMFINZI in combination with IMJUDO is indicated for the treatment of adult patients with unresectable hepatocellular carcinoma (uHCC).

IMFINZI in combination with carboplatin and paclitaxel followed by IMFINZI as a single agent is indicated for the treatment of adult patients with primary advanced or recurrent endometrial cancer that is mismatch repair deficient (dMMR) as determined by an FDA-authorized test.

IMFINZI in combination with Bacillus Calmette-Guérin (BCG) is indicated for the treatment of adult patients with BCG-naive, high-risk non-muscle-invasive bladder cancer (HR-NMIBC).

IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle-invasive bladder cancer (MIBC).

IMFINZI in combination with fluorouracil, leucovorin, oxaliplatin and docetaxel (FLOT) as neoadjuvant and adjuvant treatment, followed by single agent IMFINZI, is indicated for the treatment of adult patients with resectable gastric or gastroesophageal junction adenocarcinoma (GC/GEJC).

Please see Full Prescribing Information including Medication Guide for IMFINZI and IMJUDO.

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BICR=blinded independent central review; CI=confidence interval; cis-eligible=cisplatin-eligible; CPR=central pathology review; CrCl=creatinine clearance; EFS=event-free survival; gem-cis=gemcitabine-cisplatin; HR=hazard ratio; IO=immuno-oncology; MIBC=muscle-invasive bladder cancer; NMIBC=non–muscle-invasive bladder cancer; NR=not reached; OS=overall survival; pCR=pathological complete response; PD-L1=programmed death-ligand 1; Q3W=every 3 weeks; Q4W=every 4 weeks; RC=radical cystectomy.

AEs=adverse events; BCG=Bacillus Calmette-Guerin; BICR=blinded independent central review; CI=confidence interval; cis-eligible=cisplatin-eligible; CPR=central pathology review; CrCl=creatinine clearance; ECOG=Eastern Cooperative Oncology Group; EFS=event-free survival; gem-cis=gemcitabine-cisplatin; HR=hazard ratio; IC=immune cell; IO=immuno-oncology; ITT=intent to treat; MIBC=muscle-invasive bladder cancer; NMIBC=non–muscle-invasive bladder cancer; NR=not reached; OS=overall survival; pCR=pathological complete response; PD-L1=programmed death-ligand 1; PS=performance status; Q3W=every 3 weeks; Q4W=every 4 weeks; R=randomized; RC=radical cystectomy; TC=tumor cell; UC=urothelial carcinoma.

ALT=alanine aminotransferase; ARs=adverse reactions; AST=aspartate aminotransferase; cis-eligible=cisplatin-eligible; gem-cis=gemcitabine-cisplatin; MIBC=muscle-invasive bladder cancer; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; RC=radical cystectomy.

ALT=alanine aminotransferase; AST=aspartate aminotransferase; DRESS=Drug Rash with Eosinophilia and Systemic Symptoms;
gem-cis=gemcitabine-cisplatin; imARs=immune-mediated adverse reactions; IO=immuno-oncology; IV=intravenous; MIBC=muscle-invasive bladder cancer; Q3W=every 3 weeks; Q4W=every 4 weeks; RC=radical cystectomy; SJS=Stevens-Johnson Syndrome; TEN=toxic epidermal necrolysis; ULN=upper limit of normal; USP=United States Pharmacopeia.

Cis-eligible=cisplatin-eligible; gem-cis=gemcitabine-cisplatin; IO=immuno-oncology; MIBC=muscle-invasive bladder cancer; PD-L1=programmed death-ligand 1; RC=radical cystectomy.

References: 1. IMFINZI® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2026. 2. US Food and Drug Administration. Oncology (cancer)/hematologic malignancies approval notifications. Updated August 26, 2026. Accessed August 27, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancerhematologic-malignancies-approval-notifications 3. Powles T, Catto JWF, Galsky MD, et al. Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer. N Engl J Med. 2024;391(19):1773-1786. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Bladder Cancer V.3.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed August 6, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way.
References: 1. IMFINZI® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2026. 2. US Food and Drug Administration. Oncology (cancer)/hematologic malignancies approval notifications. Updated August 26, 2026. Accessed August 27, 2026. https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancerhematologic-malignancies-approval-notifications 3. Powles T, Catto JWF, Galsky MD, et al. Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer.
N Engl J Med. 2024;391(19):1773-1786. 4. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Bladder Cancer V.3.2026. © National Comprehensive Cancer Network, Inc. 2026. All rights reserved. Accessed August 6, 2026. To view the most recent and complete version of the guideline, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 5. Galsky M, van der Heijden MS, Catto JWF, et al. Additional efficacy and safety outcomes and an exploratory analysis of the impact of pCR on long-term outcomes from NIAGARA. Presented at: 2025 ASCO GU Cancers Symposium; February 13-15, 2025; San Francisco, CA. Session 659. 6. US Food and Drug Administration. IND application reporting: safety reports. Updated June 23, 2026. Accessed August 28, 2026. https://www.fda.gov/drugs/investigational-new-drug-ind-application-reporting-safety-reports
Reference: 1. IMFINZI® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2026.
References: 1. IMFINZI® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2026. 2. Cathomas R, Rothschild SI, Hayoz S, et al. Perioperative chemoimmunotherapy with durvalumab for muscle-invasive urothelial carcinoma: primary analysis of a single-arm phase II trial SAKK 06/17. J Clin Oncol. 2023;41(33):5131-5139. 3. Versluis JM, Long GV, Blank CU. Learning from clinical trials of neoadjuvant checkpoint blockade. Nat Med. 2020;26(4):475-484. 4. Lao CD, Khushalani NI, Angeles C, Petrella TM. Current state of adjuvant therapy for melanoma: less is more, or more is better? Am Soc Clin Oncol Educ Book. 2022;42:738-744. 5. Janjigian YY, Wolchok JD, Ariyan CE. Eradicating micrometastases with immune checkpoint blockade: strike while the iron is hot. Cancer Cell. 2021;39(6):738-742. 6. Aaes TL, Vandenabeele P. The intrinsic immunogenic properties of cancer cell lines, immunogenic cell death, and how these influence host antitumor immune response. Cell Death Differ. 2021;28(3):843-860.
References: 1. IMFINZI® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2026. 2. Powles T, Catto JWF, Galsky MD, et al. Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer. N Engl J Med. 2024;391(19):1773-1786. 3. Aragon-Ching JB, Werntz RP, Zietman AL, Steinberg GD. Multidisciplinary management of muscle-invasive bladder cancer: current challenges and future directions. Am Soc Clin Oncol Educ Book. 2018;38:307-318.

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