EFFICACY

Overall Survival

In the treatment of locally advanced or metastatic biliary tract cancers

A FIRST in BTCs: 3-year OS analysis of an approved 1L IO regimen (42.9 months median follow-up)1

PRIMARY OVERALL SURVIVAL ANALYSIS (primary endpoint)2,3*

20% REDUCTION IN THE
RISK OF DEATH

with IMFINZI + gem-cis vs gem-cis HR=0.80 (95% CI, 0.66-0.97); P=0.021

12.8-month mOS
(95% CI, 11.1-14.0)

VS icon

11.5-month mOS
(95% CI, 10.1-12.5)

  • Data cutoff was August 11, 2021

*The primary OS analysis was conducted after 424 deaths (OS maturity was 62%) with a median duration of follow-up of 16.8 months (95% CI, 14.8-17.7) with IMFINZI + gem-cis and 15.9 months (95% CI, 14.9-16.9) with gem-cis. HR based on Cox proportional hazards model stratified by disease status and primary tumor location. 2-sided P value based on a stratified log-rank test compared with alpha boundary of 0.030.

3-YEAR OVERALL SURVIVAL UPDATE (post-hoc analysis)1

26% REDUCTION IN THE RISK OF DEATH

with IMFINZI + gem-cis vs gem-cis HR=0.74 (95% CI, 0.63-0.87)

12.9-month mOS
(95% CI, 11.6-14.1)

VS icon

11.3-month mOS
(95% CI, 10.1-12.5)

3-year update KM curve 3-year update KM curve 3-year update KM curve
  • The 3-year OS analysis was conducted post hoc and not powered for statistical significance
  • Data cutoff was October 23, 2023. At the 3-year OS analysis, OS maturity was 89%

Median duration of follow-up of 42.9 months (95% CI, 39.8-44.3) for IMFINZI + gem-cis and 41.8 months (95% CI, 36.7-46.2) for gem-cis.

IMFINZI + gem-cis demonstrated consistent overall survival results across a majority of prespecified patient subgroups3

OVERALL SURVIVAL BY PRESPECIFIED SUBGROUP (primary analysis)3
Updated overall survival by prespecified subgroup chart

SWIPE FOR MORE

 

SWIPE FOR MORE

Overall survival demonstrated across patient subgroups with IMFINZI + EP
Overall survival demonstrated across patient subgroups with IMFINZI + EP
  • OS subgroup analysis was exploratory and not powered for statistical significance, including differences between or within individual subgroups

Overall survival results were assessed based on disease status at baseline4

OS RESULTS BY DISEASE STATUS (prespecified exploratory subgroup analysis)4
Initially unresectable KM curveInitially unresectable KM curve
Recurrent KM curveRecurrent KM curve
  • Exploratory analysis of prespecified subgroups; analysis was not powered to show differences between or within individual subgroups, and was not powered for statistical significance

Overall survival results were assessed in patients with and without viral hepatitis at baseline5

OS RESULTS BY VIRAL HEPATITIS STATUS (post-hoc analysis)5
Overall survival by viral hepatitis status chartOverall survival by viral hepatitis status chart
  • Post-hoc analysis of patient subgroup; analysis was not powered to show differences between or within individual subgroups, and was not powered for statistical significance

†Viral hepatitis includes previous or ongoing hepatitis B and/or previous hepatitis C infection.

‡HR calculated using an unstratified Cox proportional hazards model.

Characteristics of patients at baseline in the full analysis set and patients who were alive ≥30 months after randomization6

PATIENT CHARACTERISTICS (post-hoc analysis)6
Patient characteristics chartPatient characteristics chartPatient characteristics chart
  • Not powered for statistical significance

*Data cutoff for full analysis set was August 11, 2021.

†Data cutoff for 3-year analysis was October 23, 2023.

Progression-free Survival

In the treatment of locally advanced or metastatic biliary tract cancers

IMFINZI + gem-cis significantly reduced the risk of disease progression or death2,3

PROGRESSION-FREE SURVIVAL ANALYSIS (secondary endpoint)2,3,7*

25% REDUCTION IN THE RISK
OF DISEASE PROGRESSION
OR DEATH

with IMFINZI + gem-cis vs gem-cis HR=0.75 (95% CI, 0.63-0.89); P=0.001

7.2-month mPFS
(95% CI, 6.7-7.4)

VS icon

5.7-month mPFS
(95% CI, 5.6-6.7)

Progression-free survival (secondary endpoint) graph Overall survival by viral hepatitis status chart Overall survival by viral hepatitis status chart
  • PFS rates at 6, 9, and 12 months were descriptive endpoints and not powered for statistical significance
  • Data cutoff was August 11, 2021. Because superior OS was demonstrated at the prespecified interim analysis, PFS was formally evaluated at this time

*The primary PFS analysis was conducted after 573 events (PFS maturity was 84%) with a median duration of follow-up of 16.8 months (95% CI, 14.8-17.7) with IMFINZI + gem-cis and 15.9 months (95% CI, 14.9-16.9) with gem-cis. HR based on Cox proportional hazards model stratified by disease status and primary tumor location. 2-sided P value based on a stratified log-rank test compared with alpha boundary of 0.048.2,7

Response Rates

IMFINZI + gem-cis demonstrated confirmed responses and ongoing responses at 1 year2,3

CONFIRMED OBJECTIVE RESPONSE RATE (secondary endpoint)2,3*
Confirmed objective response rate (secondary endpoint) chartConfirmed objective response rate (secondary endpoint) chartConfirmed objective response rate (secondary endpoint) chart

*Investigator assessed according to RECIST v1.1. There was 1 patient who did not have measurable disease at baseline in the placebo group.3

  • Median DoR was 6.4 months (IQR: 4.6-17.2) with IMFINZI + gem-cis and 6.2 months (IQR: 3.8-9.0) with gem-cis3
PERCENTAGE OF ONGOING RESPONSES (secondary endpoint)3†
Percentage of ongoing responses (secondary endpoint) chartPercentage of ongoing responses (secondary endpoint) chartPercentage of ongoing responses (secondary endpoint) chart

†Investigator assessed according to RECIST v1.1. There was 1 patient who did not have measurable disease at baseline in the placebo group.3

MEDIAN TIME TO RESPONSE
(secondary endpoint)3†
Median time to response (secondary endpoint) graphicMedian time to response (secondary endpoint) graphic

†Time from the date of randomization until the date of first documented response. Analysis of time to response was based on patients in the full analysis set who had an objective response and measurable disease at baseline (n=91 for IMFINZI group and n=64 for placebo group).3

  • The analyses of ORR, DoR, ongoing responses, and median time to response were prespecified exploratory endpoints and not powered for statistical significance3

Study Design and Baseline Characteristics

TOPAZ-1 is the first positive global Phase III study in the 1L treatment of locally advanced or metastatic BTCs2,3

A randomized, double-blind, placebo-controlled, global Phase III study2,3

TOPAZ-1 STUDY DESIGN2,3
TOPAZ-1 study design diagramTOPAZ-1 study design diagram

Tumor assessments were conducted every 6 weeks for the first 24 weeks after the date of randomization, and then every 8 weeks until confirmed objective disease progression.2

*Patients who developed recurrent disease >6 months after surgery and/or completion of adjuvant therapy were eligible.2

†IMFINZI 1500 mg or placebo administered on Day 1 + gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 (each administered on Days 1 and 8) every 3 weeks (21 days) for up to 8 cycles, followed by IMFINZI 1500 mg or placebo every 4 weeks until disease progression or unacceptable toxicity. Treatment was permitted beyond disease progression if the patient was clinically stable and deriving clinical benefit as determined by the investigator.2

‡In patients weighing <30 kg, IMFINZI was administered using weight-based dosing at 20 mg/kg.3

§Investigator assessed according to RECIST v1.1.3

  • Patients with ampullary carcinoma, active or prior documented autoimmune or inflammatory disorders, HIV infection or active infections, or current or prior use of immunosuppressive medications within 14 days before the first dose of IMFINZI were ineligible to participate in the TOPAZ-1 study2

TOPAZ-1 enrolled a diverse, all-comers population with no biomarker requirements2,3

Patient demographics and disease characteristics were well balanced between treatment arms3

KEY BASELINE CHARACTERISTICS3
TOPAZ key baseline characteristics chart

SWIPE FOR MORE

 

SWIPE FOR MORE

Overall survival demonstrated across patient subgroups with IMFINZI + EP
Overall survival demonstrated across patient subgroups with IMFINZI + EP

||Disease status and disease classification missing for 1 patient.3

Patients have only locally advanced sites of disease.3

#MSI status was missing for approximately 50% of patients in each treatment group due to either an insufficient tissue sample or a test result of MSI status unknown.3

+

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 (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 Report side effects related to AstraZeneca products.

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 (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.

You may report side effects related to AstraZeneca products Report side effects related to AstraZeneca products.

SEER=Surveillance, Epidemiology, and End Results Program.

References: 1. Rizzo A, Brandi G. First-line chemotherapy in advanced biliary tract cancer ten years after the ABC-02 trial: “And yet it moves!” Cancer Treat Res Commun. 2021;27:100335. 2. Valle J, Wasan H, Palmer DH, et al. Cisplatin plus gemcitabine versus gemcitabine for biliary tract cancer. N Engl J Med. 2010;362(14):1273-1281. 3. Valle JW, Kelley RK, Nervi B, Oh DY, Zhu AX. Biliary tract cancer. Lancet. 2021;397(10272):428-444. 4. Oneda E, Hilal MA, Zaniboni A. Biliary tract cancer: current medical treatment strategies. Cancers (Basel). 2020;12(5):1237. 5. Shroff RT, Kennedy EB, Bachini M, et al. Adjuvant therapy for resected biliary tract cancer: ASCO Clinical Practice Guideline. J Clin Oncol. 2019;37(12):1015-1027. 6. Wu L, Tsilimigras DI, Paredes AZ, et al. Trends in the incidence, treatment and outcomes of patients with intrahepatic cholangiocarcinoma in the USA: facility type is associated with margin status, use of lymphadenectomy and overall survival. World J Surg. 2019;43(7):1777-1787. 7. American Cancer Society. Survival rates for bile duct cancer. Revised October 11, 2024. Accessed November 6, 2024. https://www.cancer.org/cancer/bile-duct-cancer/detection-diagnosis-staging/survival-by-stage.html 8. American Cancer Society. Survival rates for gallbladder cancer. Revised March 1, 2023. Accessed November 6, 2024. https://www.cancer.org/cancer/gallbladder-cancer/detection-diagnosis-staging/survival-rates.html

1L=first line; BTCs=biliary tract cancers; CI=confidence interval; CR=complete response; DoR=duration of response; eCCA=extrahepatic cholangiocarcinoma; ECOG=Eastern Cooperative Oncology Group; GBC=gallbladder cancer; gem-cis=gemcitabine-cisplatin; HIV=human immunodeficiency virus; HR=hazard ratio; iCCA=intrahepatic cholangiocarcinoma; IO=immuno-oncology; IQR=interquartile range; mOS=median overall survival; mPFS=median progression-free survival; MSI=microsatellite instability; NC=not calculated; NR=not reached; ORR=overall response rate; OS=overall survival; PD-L1=programmed death-ligand 1; PFS=progression-free survival; PR=partial response; PS=performance status; Q3W=every 3 weeks; Q4W=every 4 weeks; RECIST=Response Evaluation Criteria in Solid Tumors; RoW=rest of the world; TAP=tumor area positivity; TIP=tumor/immune cell positivity.

References: 1. Oh DY, He AR, Qin S, et al. Three-year survival and safety update from the phase 3 TOPAZ-1 study of durvalumab plus chemotherapy in biliary tract cancer. Poster presented at: 2024 CCF Conference; April 17-19, 2024; Salt Lake City, UT. 2. IMFINZI® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 3. Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8). doi:10.1056/EVIDoa2200015. 4. Okusaka T, Kitano M, Chen MH, et al. Outcomes by disease status in patients with advanced biliary tract cancer treated with durvalumab plus gemcitabine and cisplatin or placebo plus gemcitabine and cisplatin in the Phase 3 TOPAZ-1 study. Abstract presented at: 2022 ESMO World Congress; June 30, 2022; Barcelona, Spain. 5. Vogel A, Chen LT, He AR, et al. Regional subgroup analysis of the Phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. Abstract presented at: 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL, USA. 6. Oh DY, He AR, Qin S, et al. Three-year survival, safety and extended long-term survivor analysis from the Phase 3 TOPAZ-1 study of durvalumab plus chemotherapy in biliary tract cancer. Abstract presented at: 2024 ESMO Gastrointestinal Cancers Annual Congress; June 27, 2024; Munich, Germany. 7. Oh DY, He AR, Qin S, et al. A phase 3 randomized, double-blind, placebo-controlled study of durvalumab in combination with gemcitabine plus cisplatin in patients with advanced biliary tract cancer: TOPAZ-1. Abstract presented at: 2022 ASCO Gastrointestinal Cancers Symposium. January 20-22, 2022; San Francisco, CA.

BEP=biomarker-evaluable patients; BTCs=biliary tract cancers; CI=confidence interval; EORTC=European Organization for Research and Treatment of Cancer; ERBB2=erhthroblastic oncogene B-2; gem-cis=gemcitabine-cisplatin; GHS=global health status; HER2=human epidermal growth factor receptor 2; HR=hazard ratio; NC=not calculated; OS=overall survival; PROs=patient-reported outcomes; QLQ-BIL21=21-item Cholangiocarcinoma and Gallbladder Cancer Quality of Life Questionnaire; QLQ-C30=30-item Quality of Life Questionnaire; QoL=quality of life.

References: 1. Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8). doi:10.1056/EVIDoa2200015. 2. Oh DY, Valle JW, Qin S, et al. Impact of mutation status on efficacy outcomes in TOPAZ-1: a phase 3 study of durvalumab or placebo plus gemcitabine and cisplatin in advanced biliary tract cancer. Presented at: 2022 ESMO Asia Congress; December 2-4, 2022; Singapore, Republic of Singapore. 3. Bridgewater JA, Goodman KA, Kalyan A, Mulcahy MF. Biliary tract cancer: epidemiology, radiotherapy, and molecular profiling. Am Soc Clin Oncol Educ Book. 2016;35:e194-e203. 4. Burris H, Okusaka T, Vogel A, et al. Patient-reported outcomes for the phase 3 TOPAZ-1 study of durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. Poster presented at: 2022 ASCO Annual Meeting; June 3-7, 2022; Chicago, IL.

1L=first line; CI=confidence interval; gem-cis=gemcitabine-cisplatin; HR=hazard ratio; IO=immuno-oncology; NCCN®=National Comprehensive Cancer Network®(NCCN®); OS=overall survival; PFS=progression-free survival.

References: 1. IMFINZI® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 2. Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8). doi:10.1056/EVIDoa2200015. 3. US Food and Drug Administration. Oncology (cancer)/hematologic malignancies approval notifications. Updated October 29, 2024. Accessed October 30, 2024. https://www.fda.gov/drugs/resources-information-approved-drugs/oncology-cancerhematologic-malignancies-approval-notifications 3. US Food and Drug Administration. Oncology (cancer)/
hematologic malignancies approval notifications. Updated October 29, 2024. Accessed October 30, 2024. https://
www.fda.gov/drugs/resources-information-approved-drugs/
oncology-cancerhematologic-malignancies-approval-notifications 4. Oh DY, He AR, Qin S, et al. Three-year
survival and safety update from the phase 3 TOPAZ-1 study of durvalumab plus chemotherapy in biliary tract cancer. Poster presented at: 2024 CCF Conference; April 17-19, 2024; Salt Lake City, UT. 5. Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Biliary Tract Cancers V.4.2024. ©National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed August 29, 2024. To view the most recent and complete version of the guideline, go online to NCCN.org.

ALT=alanine aminotransferase; AST=aspartate aminotransferase; DRESS=Drug Rash with Eosinophilia and Systemic Symptoms; Gem-cis=gemcitabine-cisplatin; imARs=immune-mediated adverse reactions; IV=intravenous; Q3W=every 3 weeks; Q4W=every 4 weeks; SJS=Stevens-Johnson Syndrome; TEN=toxic epidermal necrolysis; ULN=upper limit of normal; USP=United States Pharmacopeia.

Reference: 1. IMFINZI® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024.

ALT=alanine aminotransferase; ARs=adverse reactions; AST=aspartate aminotransferase; BTCs=biliary tract cancers; gem-cis=gemcitabine-cisplatin; imARs=immune-mediated adverse reactions; mTTO=median time to onset; NCI CTCAE=National Cancer Institute Common Terminology Criteria for Adverse Events.

References: 1. Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evid. 2022;1(8). doi:10.1056/EVIDoa2200015. 2. IMFINZI® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 3. Oh DY, He AR, Qin S, et al. Three-year survival and safety update from the phase 3 TOPAZ-1 study of durvalumab plus chemotherapy in biliary tract cancer. Poster presented at: 2024 CCF Conference; April 17-19, 2024; Salt Lake City, UT. 4. Antonuzzo L, Takahashi H, Oh Park J, et al. Immune-mediated adverse event incidence, timing and association with efficacy in the phase 3 TOPAZ-1 study of durvalumab or placebo plus gemcitabine and cisplatin in advanced biliary tract cancer. Presented at: 2022 ESMO Congress; September 9-13, 2022; Paris, France.

1L=first-line; CI=confidence interval; ECOG=Eastern Cooperative Oncology Group; gem-cis=gemcitabine-cisplatin; HR=hazard ratio; mOS=median overall survival; mPFS=median progression-free survival; OS=overall survival; PFS=progression-free survival; PS=performance status; Q3W=every 3 weeks; Q4W=every 4 weeks.

References: 1. Rimini M, Fornaro L, Rizzato MD, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer: A large real-life worldwide population. Eur J Canc.
 2024;208(114199). 2. IMFINZI® (durvalumab) [Prescribing Information]. Wilmington, DE: AstraZeneca Pharmaceuticals LP; 2024. 3. Rimini M, Masi G, Lonardi S, et al. Durvalumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin in biliary tract cancer: a real‑world retrospective, multicenter study. Target Oncol. 2024;19(3):359-370.