EFFICACY

See HIMAYALA trial results in patients with unresectable HCC

Results from the HIMALAYA study include primary OS data, ~6-year OS follow-up analysis (post hoc), and OS data for subgroups by liver function (exploratory)

Overall Survival

In unresectable hepatocellular carcinoma

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

STATISTICALLY SUPERIOR OS (primary analysis)^1,2,4

16.4 months mOS with IMFINZI + IMJUDO

(95% CI, 14.2-19.6)

13.8 months mOS with sorafenib

(95% CI, 12.3-16.1)

The hazard ratio was 0.78 (95% CI, 0.66-0.92) with a P value of 0.0035.

The HR is based on the stratified Cox proportional hazard model. The P value is based on a stratified log-rank test and a Lan-DeMets alpha spending function with O'Brien-Fleming-type boundary and the actual number of events observed. The boundary for declaring statistical significance for IMFINZI + IMJUDO vs sorafenib was 0.0398. Median duration of follow-up was 33.2 months (range: 31.7-34.5) for IMFINZI + IMJUDO and 32.2 months (range: 30.4-33.7) for sorafenib. Data cutoff: August 27, 2021.

What were the results of the 5-year and ~6-year follow-up (post-hoc) analyses for HIMALAYA?

5-YEAR OS FOLLOW-UP (post-hoc analysis)⁵

16.4 months mOS with IMFINZI + IMJUDO

(95% CI, 14.2-19.6)

13.8 months mOS with sorafenib

(95% CI, 12.3-16.1)

The hazard ratio was 0.76 (95% CI, 0.65-0.89); not powered for statistical significance.

In the post-hoc analysis, median duration of follow-up was 62.5 months (range: 59.5-64.8) for IMFINZI + IMJUDO and 59.9 months (range: 58.3-61.5) for sorafenib. OS data maturity across the IMFINZI + IMJUDO and sorafenib arms was 82%. Data cutoff: March 1, 2024.

IMFINZI + IMJUDO is the FIRST & ONLY first-line immunotherapy regimen in uHCC with BEYOND 5 years of OS data^1-3

A first in uHCC: ONLY IMFINZI + IMJUDO has BEYOND 5 years of follow-up in the 1L treatment of adults with uHCC^1-3

NEW ~6-YEAR OS UPDATE (post-hoc analysis)³

Nearly 2x more patients were estimated to be alive at ~6years

At the time of the ~6-year post-hoc analysis, mOS was 16.4 months (95% CI, 14.2-19.6) with IMFINZI + IMJUDO and 13.8 months (95% CI, 12.3-16.1) with sorafenib (HR=0.76 [95% CI, 0.65-0.89])
The ~6-year post-hoc analysis, including landmark OS rates, was not powered for statistical significance. Estimates of OS rates at 60 and 72 months were calculated using Kaplan-Meier technique
In the post-hoc analysis, median duration of follow-up was 71.3 months (range: 6.2-85.0) for IMFINZI + IMJUDO and 38.3 months (range: 0.03-83.3) for sorafenib

Data cutoff: March 3, 2025.

IMFINZI + IMJUDO set the ~6-year benchmark for OS data with a 1L dual-IO regimen in uHCC^1-3

Additional post-hoc data from the HIMALAYA study include:

OS by subgroup
OS by baseline liver function
OS by disease etiology

What were the OS results across patient subgroups from the 5-year follow-up analysis (post-hoc)?

In the HIMALAYA study, IMFINZI + IMJUDO demonstrated consistent OS data across most prespecified subgroups

OVERALL SURVIVAL BY PRESPECIFIED SUBGROUP (post-hoc analysis)⁵

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For all patients, OS HRs and 95% CIs were calculated using a Cox proportional hazard model adjusting for treatment, etiology, ECOG PS, and MVI. For the subgroup analysis, the HR and 95% CI were estimated from an unstratified Cox proportional hazard model with treatment as the only covariate and using the Efron method to control for ties.

*Stratification factors.

Post-hoc OS analysis of prespecified subgroups was not powered to show differences between or within individual subgroups and was not powered for statistical significance⁴

What were the OS results from the 5-year post-hoc analysis for ALBI Grade 1 and Grade 2/3 patient subgroups?

Post-hoc analysis; not powered for statistical significance⁶

5-YEAR OS DATA BY BASELINE ALBI GRADE (post-hoc analysis)^6†

HIMALAYA Regimen 5-Year OS Data by Baseline ALBI Grade

^†Data cutoff: March 1, 2024.

^‡ALBI grade data not available for 1 participant.

^§One participant in the IMFINZI + IMJUDO arm and 1 participant in the sorafenib arm were classified as ALBI Grade 3 at baseline.

Refer to Kudo M, et al. 2024.

The ALBI grade subgroup analysis was post hoc and not powered for statistical significance⁶

IMFINZI + IMJUDO is the FIRST & ONLY dual-IO therapy in uHCC with
5-year OS data in patients across ALBI grades at baseline^1,2,6,7

What are the ALBI grades of liver dysfunction in unresectable HCC?

ALBUMIN-BILIRUBIN (ALBI) GRADING⁸

Table showing the Albumin-Bilirubin Grading System for calculating 3 levels of liver dysfunction severity

See Child-Pugh and ALBI data across 3+ years of treatment with
IMFINZI + IMJUDO⁸ Post-hoc analysis; not powered for statistical significance.

How many patients in the HIMALAYA study had viral hepatitis vs nonviral disease etiology?

Disease etiologies in the HIMALAYA study were well balanced between arms⁴

BASELINE DISEASE ETIOLOGY⁴

Image of 2 bar charts showing the balance of disease etiology for patients enrolled in the IMFINZI + IMJUDO arm and the sorafenib arm of the HIMALAYA trial

^||No active viral hepatitis identified.

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^||No active viral hepatitis identified.

What were the 5-year OS results for patients with viral or nonviral etiology?

Overall survival results at 5 years were consistent across etiological subgroups⁵

5-YEAR OS RESULTS BY ETIOLOGY (post-hoc analysis)⁵

Forest plot showing consistent 5-year survival across patients with HBV, HCV, and nonviral disease etiology in the HIMALAYA study

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Post-hoc OS analysis of prespecified subgroups was not powered to show differences between or within individual subgroups and was not powered for statistical significance⁴

^¶The hazard ratio and 95% CI from the crude model are estimated from an unstratified Cox proportional hazards model with treatment as the only covariate and using the Efron method to control for ties.

^#The hazard ratio and 95% CI from the stratified model are estimated from a stratified Cox proportional hazards model adjusting for EHS (no vs yes/missing), ALBI grade (1 vs 2/3), and using the Efron method to control for ties.

**Values of etiology of liver disease (HBV vs HCV vs others/nonviral) are obtained from the pathology at screening.

^††One participant was removed due to missing ALBI score.

What were the characteristics of patients treated with IMFINZI + IMJUDO at baseline and at the 5-year update?

A post-hoc analysis was performed to characterize the patients surviving ≥48 months after randomization^‡‡

CHARACTERISTICS OF PATIENTS TREATED WITH IMFINZI + IMJUDO AT THE 5-YEAR UPDATE AND AT BASELINE IN THE FULL ANALYSIS SET
(post-hoc analysis)^4,5,9

Tornado plot showing that characteristics were similar for patients at baseline and those achieving long-term survival in the HIMALAYA study

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HBV: Patients who tested positive for HBsAg or anti-HBcAb with detectable HBV DNA. HCV: Patients who tested positive for HCV or had a history of HCV infection. Nonviral: No active viral hepatitis identified. Viral etiology, MVI, and/or EHS determined at screening. BCLC determined at study entry.

^‡‡Data cutoff: March 1, 2024.^4,5,9

In the IMFINZI + IMJUDO arm, characteristics of patients at the 5-year update were generally consistent with those of the population at baseline^4,5,9

See the study design for the Phase III HIMALAYA study

Objective Response Rate, Duration
of Response, and Time to Response

In the first-line treatment of unresectable HCC

What was the objective response rate with IMFINZI + IMJUDO and sorafenib at primary analysis?

In the HIMALAYA study, the ORR was 20.1% with IMFINZI + IMJUDO and 5.1% with sorafenib.^1,2,4

CONFIRMED OBJECTIVE RESPONSE RATE IN THE
INTENT-TO-TREAT POPULATION (secondary endpoint)^1,2,4*

Objective Response Rate with IMFINZI + IMJUDO and Sorafenib

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*Based on Clopper-Pearson method.

Confirmed responses by investigator assessment according to RECIST v1.1. Not powered for statistical significance⁴

The disease control rate^† was 60.1% with IMFINZI + IMJUDO and 60.7% with sorafenib. Not powered for statistical significance.⁴

^†Disease control rate is the sum of complete response rate, partial response rate, and stable disease rate.⁴

What was the duration of response and time to response with IMFINZI + IMJUDO and sorafenib at primary analysis?

In the HIMALAYA study, the median DoR was 22.3 months with IMFINZI + IMJUDO and 18.4 months with sorafenib. The median TTR was 2.2 months with IMFINZI + IMJUDO and 3.8
months with sorafenib.^1,2,4

MEDIAN DURATION OF RESPONSE
(secondary endpoint)^1,2,4

Duration of Response for IMFINZI + IMJUDO and Sorafenib

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Duration of response was defined as the time from first documentation of response until the date of progression, death, or the last evaluable RECIST assessment for patients who had not progressed. Not powered for statistical significance⁴
The percentage of patients with duration of response ≥6 months was 82.3% with IMFINZI + IMJUDO and 78.9% with sorafenib^1,2
The percentage of patients with duration of response ≥12 months was 65.8% with IMFINZI + IMJUDO and 63.2% with sorafenib^1,2

MEDIAN TIME TO RESPONSE
(secondary endpoint)⁴

Median Time to Response for IMFINZI + IMJUDO and Sorafenib

Time to response was defined as the time from randomization to first confirmed response according to RECIST assessment. Not powered for statistical significance⁴

Median progression-free survival was 3.8 months (95% CI, 3.7-5.3) with IMFINZI + IMJUDO and 4.1 months (95% CI, 3.7-5.5) with sorafenib (HR=0.90 [95% CI, 0.77-1.05]); PFS was not statistically significant^1,2‡

^‡The HR is based on the stratified Cox proportional hazard model.^1,2

Study Design and Patient Characteristics

What was the HIMALAYA study design?

HIMALAYA was a Phase III, open-label, multicenter, global study that evaluated IMFINZI + IMJUDO for overall survival
vs sorafenib in the first-line treatment of unresectable HCC^1,2,4

STRIDE (Single Tremelimumab Regular Interval Durvalumab) is the name given to the IMFINZI + IMJUDO regimen evaluated in the HIMALAYA study⁴

STUDY DESIGN: PHASE III, OPEN-LABEL, MULTICENTER, GLOBAL STUDY^1,2,4

Himalaya Study Design and Patient Characteristics

Treatment continued until disease progression or unacceptable toxicity. Patients in all arms could continue to receive treatment after evidence of disease progression if, in the investigator’s opinion, they were still benefiting from treatment and continued to meet inclusion and exclusion criteria.

*The HIMALAYA study included an additional arm of therapy: The IMJUDO 75-mg + IMFINZI arm (n=153) was closed following a preplanned analysis of a Phase II study. Results from this arm are not reported in this material, and this dosing regimen is not approved for use.⁴

The HIMALAYA study included patients with BCLC B or C disease, ECOG PS 0 or 1, and Child-Pugh A classification⁴

What were the key exclusion criteria for
the HIMALAYA study?^1,2,4

Clinically meaningful ascites or hepatic encephalopathy
Portal vein tumor thrombosis of the main trunk
Active or prior GI bleeding within the past 12 months
Active or prior documented autoimmune or inflammatory disorders
HBV and HCV coinfection

What were the primary, secondary, and exploratory endpoints for the HIMALAYA study?

Primary endpoint: Overall survival for IMFINZI + IMJUDO was evaluated for statistical superiority vs sorafenib^1,2,4
Select secondary endpoints^†: OS rates at 18, 24, and 36 months (primary analysis); PFS, ORR, DoR, safety, and PROs^1,2,4
Select exploratory endpoints: OS rates at 18, 24, 36, 48, 60, and 72 months (48-, 60-, and 72-month timepoints are post-hoc analyses)³

Is EGD required to start treatment with IMFINZI + IMJUDO? No EGD was required to initiate therapy in the HIMALAYA study^1,2,4‡

^†PFS, ORR, and DoR were investigator assessed according to RECIST v1.1. Tumor assessments were conducted every 8 weeks for the first 12 months and then every 12 weeks thereafter.^1,2,4

^‡No EGD was required to screen for esophageal varices for trial eligibility. Patients with active or prior documented GI bleeding within 12 months were excluded. For patients with a history of GI bleeding for greater than 12 months or assessed as high risk for esophageal variceal, adequate endoscopic therapy was required.^1,2,4

The HIMALAYA study is the largest positive Phase III trial to evaluate IO therapy as 1L treatment of unresectable HCC^4,10

Patient demographics and disease characteristics were well balanced between arms⁴

BASELINE DEMOGRAPHICS AND DISEASE CHARACTERISTICS⁴

Table listing the demographics and characteristics of patients in the HIMALAYA study at baseline, including age, region, ECOG score, and BCLC stage

^§Includes Brazil, Canada, France, Germany, Italy, Japan, Russia, Spain, Ukraine, and the United States.

^||None of the above.

^¶No active viral hepatitis identified.

^#Baseline PD-L1 results were not available for patients who were randomized but not treated. PD-L1 expression level was based on the tumor and immune cell positivity score method as PD-L1 positive (≥1%) or negative (<1%).

IMFINZI + IMJUDO significantly improved OS vs sorafenib in the Phase III HIMALAYA study^1,2,4:

22% reduction in risk of death (HR=0.78 [95% CI, 0.66-0.92]; P=0.0035)

mOS was 16.4 months with IMFINZI + IMJUDO vs 13.8 months with sorafenib

IMFINZI + IMJUDO is the FIRST & ONLY 1L IO regimen in uHCC with BEYOND 5 years of OS data (post-hoc analysis; not powered for statistical significance)^1-3 *

OS rates at 6 years were 17.1% with IMFINZI + IMJUDO and 8.9% with sorafenib
mOS was 16.4 months (95% CI, 14.2-19.6) with IMFINZI + IMJUDO and 13.8 months (95% CI, 12.3-16.1) with sorafenib (HR=0.76 [95% CI, 0.65-0.89])

The FIRST & ONLY dual immunotherapy in uHCC with 5-year OS data by ALBI Grade at baseline (post-hoc analysis)^1,2,6,7

*mDOF: 71.3 months (range: 6.2-85.0) for IMFINZI + IMJUDO and 38.3 months (range: 0.03-83.3) for sorafenib. DCO: March 3, 2025.³

View safety information

HOME PATIENT-REPORTED OUTCOMES

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:

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 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 Bacillus Calmette-Guérin (BCG) is indicated for the treatment of adult patients with BCG-naive, high-risk non-muscle-invasive bladder cancer (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 (Thyroiditis, Hyperthyroidism, and Hypothyroidism): 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.
Other (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.

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-Naïve, High-Risk Non-Muscle-Invasive Bladder Cancer (NMIBC)

In patients with BCG-naïve, high-risk 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-naïve, high-risk 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.

You may report side effects related to AstraZeneca products .

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

Indications:

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

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

You may report side effects related to AstraZeneca products .

1L=first line; BID=twice a day; CI=confidence interval; HCC=hepatocellular carcinoma; HR=hazard ratio; mDOF=median duration of follow-up; mOS=median overall survival; OS=overall survival; PO=by mouth; Q4W=every 4 weeks; uHCC=unresectable hepatocellular carcinoma.

References: 1. IMFINZI^® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2025. 2. IMJUDO^® (tremelimumab-actl) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 3. Sangro B, Qin S, Kelley RK, et al. Pooled efficacy and safety outcomes with tremelimumab plus durvalumab in participants with unresectable hepatocellular carcinoma from the combined China extension and global cohorts in the Phase 3 HIMALAYA study. Poster presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Poster 1494P. 4. Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022;1(8). doi:10.1056/EVIDoa2100070.

1L=first line; AFP=alpha-fetoprotein; ALBI=albumin-bilirubin; BCLC=Barcelona Clinic Liver Cancer; BID=twice a day; CI=confidence interval; CR=complete response; DCO=data cutoff; DoR=duration of response; ECOG=Eastern Cooperative Oncology Group; EGD=esophagogastroduodenoscopy; EHS=extrahepatic spread; GI=gastrointestinal; HBcAb=hepatitis B core antibody; HBsAg=hepatitis B surface antigen; HBV=hepatitis B virus; HCC=hepatocellular carcinoma; HCV=hepatitis C virus; HR=hazard ratio; IO=immuno-oncology; IV=intravenous; mDOF=median duration of follow-up; mOS=median overall survival; MVI=macrovascular invasion; NR=not reached; ORR=objective response rate; OS=overall survival; PD-L1=programmed death-ligand 1; PFS=progression-free survival; PO=by mouth; PR=partial response; PROs=patient-reported outcomes; PS=performance status; Q4W=every 4 weeks; R=randomized; RECIST=Response Evaluation Criteria in Solid Tumors; TTR=time to response; uHCC=unresectable hepatocellular carcinoma.

References: 1. IMFINZI^® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2025. 2. IMJUDO^® (tremelimumab-actl) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 3. Sangro B, Qin S, Kelley RK, et al. Pooled efficacy and safety outcomes with tremelimumab plus durvalumab in participants with unresectable hepatocellular carcinoma from the combined China extension and global cohorts in the Phase 3 HIMALAYA study. Poster presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Poster 1494P. 4. Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022;1(8). doi:10.1056/EVIDoa2100070. 5. Rimassa L, Chan SL, Sangro B, et al. Five-year overall survival update from the HIMALAYA study of tremelimumab plus durvalumab in unresectable HCC. J Hepatol. 2025;83(4):899-908. 6. Kudo M, Rimassa L, Chan SL, et al. Five-year overall survival (OS) and OS by baseline liver function from the phase 3 HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. Presented at: 2024 ESMO Asia Congress; December 6-8, 2024; Singapore. 7. Sangro B, Kudo M, Decaens T, et al. Outcomes by liver function in patients with unresectable hepatocellular carcinoma treated with nivolumab plus ipilimumab vs lenvatinib or sorafenib in the CheckMate 9DW trial. Abstract presented at: 2025 EASL Congress; May 8, 2025; Amsterdam, Netherlands. Published in J Hepatol. 2025;82(S1):23. Abstract GS-005. 8. Vogel A, Chan SL, Furuse J, et al. Outcomes by baseline liver function in patients with unresectable hepatocellular carcinoma treated with tremelimumab and durvalumab in the phase 3 HIMALAYA study. Poster presented at: ESMO World Congress on Gastrointestinal Cancer; June 30, 2022; Barcelona, Spain. 9. Rimassa L, Chan SL, Sangro B, et al. Five-year overall survival (OS) and OS by tumour response measures from the phase III HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma (uHCC). Presented at: 2024 ESMO Congress; September 13-17, 2024; Barcelona, Spain. Session 947MO. 10. Fulgenzi CA, D’Alessio A, Airoldi C, et al. Comparative efficacy of novel combination strategies for unresectable hepatocellular carcinoma: a network metanalysis of phase III trials. Eur J Cancer. 2022;174:57-67.

ACTH=adrenocorticotropic hormone; ALBI=albumin-bilirubin; ALT=alanine aminotransferase; AR=adverse reaction; AST=aspartate aminotransferase; HCC=hepatocellular carcinoma; imAR=immune-mediated adverse reaction; INR=international normalized ratio; IO=immuno-oncology; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; SMQ=Standardised MedDRA Query; uHCC=unresectable hepatocellular carcinoma.

References: 1. IMFINZI^® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2025. 2. IMJUDO^® (tremelimumab-actl) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 3. Sangro B, Qin S, Kelley RK, et al. Pooled efficacy and safety outcomes with tremelimumab plus durvalumab in participants with unresectable hepatocellular carcinoma from the combined China extension and global cohorts in the Phase 3 HIMALAYA study. Poster presented at: 2025 ESMO Congress; October 17-21, 2025; Berlin, Germany. Poster 1494P. 4. Abou-Alfa GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022;1(8). doi:10.1056/EVIDoa2100070. 5. Sangro B, Kudo M, Decaens T, et al. Outcomes by liver function in patients with unresectable hepatocellular carcinoma treated with nivolumab plus ipilimumab vs lenvatinib or sorafenib in the CheckMate 9DW trial. Abstract presented at: 2025 EASL Congress; May 8, 2025; Amsterdam, Netherlands. Published in J Hepatol. 2025;82(S1):23. Abstract GS-005. 6. Vogel A, Chan SL, Furuse J, et al. Outcomes by baseline liver function in patients with unresectable hepatocellular carcinoma treated with tremelimumab and durvalumab in the phase 3 HIMALAYA study. Poster presented at: ESMO World Congress on Gastrointestinal Cancer; June 30, 2022; Barcelona, Spain. 7. Abou-Alfa GK, Chan SL, Kudo M, et al. Phase 3 randomized, open-label, multicenter study of tremelimumab and durvalumab as first-line therapy in patients with unresectable hepatocellular carcinoma: HIMALAYA. Presented at: ASCO Gastrointestinal Cancers Symposium; January 20-22, 2022; San Francisco, CA. 8. Lau G, Sangro B, Crysler OV, et al. Temporal patterns of immune-mediated adverse events with tremelimumab plus durvalumab in the phase 3 HIMALAYA study in unresectable hepatocellular carcinoma. Poster presented at: American Society of Clinical Oncology Annual Meeting; June 2-6, 2023; Chicago, IL.

CI=confidence interval; ECOG=Eastern Cooperative Oncology Group; EORTC=European Organisation for Research and Treatment of Cancer; GHS=global health status; HCC=hepatocellular carcinoma; HR=hazard ratio; HRQoL=health-related quality of life; MVI=macrovascular invasion; PROs=patient-reported outcomes; PS=performance status; QLQ-C30=30-item Quality of Life Questionnaire; QLQ-HCC18=18-item HCC Health-Related Quality of Life Questionnaire; QoL=quality of life; TTD=time to deterioration.

References: 1. Abou-Alfa, GK, Lau G, Kudo M, et al. Tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. NEJM Evid. 2022;1(8). doi:10.1056/EVIDoa2100070. 2. Sangro B, Galle PR, Kelley RK, et al. Patient-reported outcomes from the phase 3 HIMALAYA study of tremelimumab plus durvalumab in unresectable hepatocellular carcinoma. J Clin Oncol. Published online May 28, 2024. doi: 10.1200/JCO.23.01462.

1L=first line; ALT=alanine aminotransferase; ARs=adverse reactions; AST=aspartate aminotransferase; CTLA-4=cytotoxic T-lymphocyte–associated protein 4; DRESS=Drug Rash with Eosinophilia and Systemic Symptoms; EGD=esophagogastroduodenoscopy; GI=gastrointestinal; HCC=hepatocellular carcinoma; imARs=immune-mediated adverse reactions; IV=intravenous; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events; PD-L1=programmed death-ligand 1; Q4W=every 4 weeks; SJS=Stevens-Johnson Syndrome; TEN=toxic epidermal necrolysis; uHCC=unresectable hepatocellular carcinoma; ULN=upper limit of normal; USP=United States Pharmacopeia.

CD28=cluster of differentiation 28; CD80/86=cluster of differentiation 80/86; CTLA-4=cytotoxic T-lymphocyte–associated protein 4; HCC=hepatocellular carcinoma; PD-1=programmed cell death protein 1; PD-L1=programmed death-ligand 1; TME=tumor microenvironment.

References: 1. IMFINZI^® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. IMJUDO^® (tremelimumab-actl) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 3. Chen L, Flies DB. Molecular mechanisms of T cell co-stimulation and co-inhibition [published correction appears in Nat Rev Immunol. 2013;13(7):542]. Nat Rev Immunol. 2013;13(4):227-242. 4. Waldman AD, Fritz JM, Lenardo MJ. A guide to cancer immunotherapy: from T cell basic science to clinical practice. Nat Rev Immunol. 2020;20(11):651-668. 5. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by CTLA-4 blockade. Science. 1996;271(5256):1734-1736. 6. Kelley RK, Sangro B, Harris W, et al. Safety, efficacy, and pharmacodynamics of tremelimumab plus durvalumab for patients with unresectable hepatocellular carcinoma: randomized expansion of a phase I/II study. J Clin Oncol. 2021;39(27):2991-3001.

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IMFINZI and IMJUDO are registered trademarks and AstraZeneca Access 360 is a trademark of the AstraZeneca group of companies.

See HIMAYALA trial results in patients with unresectable HCC

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

What were the results of the 5-year and ~6-year follow-up (post-hoc) analyses for HIMALAYA?

Additional post-hoc data from the HIMALAYA study include:

What were the OS results across patient subgroups from the 5-year follow-up analysis (post-hoc)?

In the HIMALAYA study, IMFINZI + IMJUDO demonstrated consistent OS data across most prespecified subgroups

What were the OS results from the 5-year post-hoc analysis for ALBI Grade 1 and Grade 2/3 patient subgroups?

What are the ALBI grades of liver dysfunction in unresectable HCC?

How many patients in the HIMALAYA study had viral hepatitis vs nonviral disease etiology?

Disease etiologies in the HIMALAYA study were well balanced between arms4

What were the 5-year OS results for patients with viral or nonviral etiology?

Overall survival results at 5 years were consistent across etiological subgroups5

What were the characteristics of patients treated with IMFINZI + IMJUDO at baseline and at the 5-year update?

A post-hoc analysis was performed to characterize the patients surviving ≥48 months after randomization‡‡

In the IMFINZI + IMJUDO arm, characteristics of patients at the 5-year update were generally consistent with those of the population at baseline4,5,9

What was the objective response rate with IMFINZI + IMJUDO and sorafenib at primary analysis?

In the HIMALAYA study, the ORR was 20.1% with IMFINZI + IMJUDO and 5.1% with sorafenib.1,2,4

What was the duration of response and time to response with IMFINZI + IMJUDO and sorafenib at primary analysis?

In the HIMALAYA study, the median DoR was 22.3 months with IMFINZI + IMJUDO and 18.4 months with sorafenib. The median TTR was 2.2 months with IMFINZI + IMJUDO and 3.8 months with sorafenib.1,2,4

What was the HIMALAYA study design?

The HIMALAYA study is the largest positive Phase III trial to evaluate IO therapy as 1L treatment of unresectable HCC4,10

IMFINZI + IMJUDO significantly improved OS vs sorafenib in the Phase III HIMALAYA study1,2,4:

SEE FULL INDICATIONS

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Indications:

IMPORTANT SAFETY INFORMATION

Severe and Fatal Immune-Mediated Adverse Reactions

Indications:

Immune-Mediated Pneumonitis

Immune-Mediated Colitis

Immune-Mediated Hepatitis

Immune-Mediated Endocrinopathies

Immune-Mediated Nephritis with Renal Dysfunction

Immune-Mediated Dermatology Reactions

Immune-Mediated Pancreatitis

Other Immune-Mediated Adverse Reactions

Infusion-Related Reactions

Complications of Allogeneic HSCT after IMFINZI

Embryo-Fetal Toxicity

Lactation

Adverse Reactions

Indications:

Disease etiologies in the HIMALAYA study were well balanced between arms⁴

Overall survival results at 5 years were consistent across etiological subgroups⁵

A post-hoc analysis was performed to characterize the patients surviving ≥48 months after randomization^‡‡

In the IMFINZI + IMJUDO arm, characteristics of patients at the 5-year update were generally consistent with those of the population at baseline^4,5,9

In the HIMALAYA study, the ORR was 20.1% with IMFINZI + IMJUDO and 5.1% with sorafenib.^1,2,4

In the HIMALAYA study, the median DoR was 22.3 months with IMFINZI + IMJUDO and 18.4 months with sorafenib. The median TTR was 2.2 months with IMFINZI + IMJUDO and 3.8
months with sorafenib.^1,2,4

The HIMALAYA study is the largest positive Phase III trial to evaluate IO therapy as 1L treatment of unresectable HCC^4,10

IMFINZI + IMJUDO significantly improved OS vs sorafenib in the Phase III HIMALAYA study^1,2,4:

Severe and Fatal Immune-Mediated
Adverse Reactions

Severe and Fatal Immune-Mediated
Adverse Reactions