Summary
IMFINZI® + gem-cis: Standard of Care
in the 1L treatment of aBTC2,3
The approved IO regimen that significantly extends OS and PFS*4
Unprecedented 3-year OS data (14.6% vs. 6.9%)*5
Similar rates of adverse events with IMFINZI® + gem-cis and gem-cis4
* All data compare IMFINZI® + gem-cis vs. gem-cis.
aBTC=advanced biliary tract cancer; cis=cisplatin; gem=gemcitabine; IO=immuno-oncology; L=line of treatment; OS=overall survival; PFS=progression-free survival.
Study design
TOPAZ-1: The first positive global Phase III study for an IO combination in 1L advanced BTC1,4
A randomised, double-blind, placebo-controlled, global Phase III study of IMFINZI® + gem-cis vs gem-cis4
TOPAZ-1 STUDY DESIGN4
Patient population
- Adults (≥18 years) with unresectable, locally advanced or metastatic BTC including:
– iCCA
– eCCA
– GBC - Previously untreated if unresectable or metastatic at initial diagnosis
- Recurrent disease >6 months after surgery and/or completion of adjuvant therapy
- ECOG PS 0 or 1
- 1 target lesion by RECIST v1.1
Stratification factors
- Disease status (initially unresectable vs recurrent)
- Primary tumour location (iCCA vs eCCA vs GBC)
Primary endpoint
- Overall survival (OS)
Secondary endpoints included:
- Progression-free survival (PFS)
- Objective response rate (ORR)
- Duration of response (DoR)
- Efficacy by PD-L1 status
- Safety
Exclusion criteria included patients with ampullary carcinoma, with brain metastases, active or prior documented autoimmune or inflammatory disorders, HIV infection or active infections including tuberculosis or hepatitis C or patients with current or prior use of immunosuppressive medication within 14 days before the first dose of IMFINZI®. Patients with active HBV were eligible if they were on antiviral therapy4
* IMFINZI® 1500 mg or placebo was 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 clinical or imaging disease progression (per RECIST v1.1) or until unacceptable toxicity, withdrawal of consent or any other discontinuation criteria were met. Administration of study treatment was permitted beyond disease progression if the patient was clinically stable and deriving clinical benefit as determined by the investigator.4
BTC=biliary tract cancer; cis=cisplatin; eCCA=extrahepatic cholangiocarcinoma; ECOG=Eastern Cooperative Oncology Group; GBC=gallbladder cancer; gem=gemcitabine; HBV=hepatitis B virus; HIV=human immunodeficiency virus; iCCA=intrahepatic cholangiocarcinoma; IO=immuno-oncology; L=Line of treatment; OS=overall survival; PDL1=programmed death-ligand 1; PS=performance status; Q3W=once every 3 weeks; Q4W=once every 4 weeks; R=randomisation; RECIST=Response Evaluation Criteria in Solid Tumours.
Patient demographics and disease characteristics were generally balanced between treatment arms4
Patients were stratified by primary tumour location and disease status at baseline4
KEY BASELINE CHARACTERISTICS4
Adapted from Oh DY et al., 2022.4
Patients were eligible regardless of PD-L1 expression or mutation status4
* Patient has only locally advanced sites of disease.4
# MSI status was missing for ~50% of patients in each treatment group due to either an insufficient tissue sample or a test result of MSI status unknown.4
cis=cisplatin; ECOG=Eastern Cooperative Oncology Group; gem=gemcitabine; MSI=microsatellite instability; PD-L1=programmed death-ligand 1; PS=performance status; TAP=tumour area positivity.
Results
IMFINZI® + gem-cis is the first IO combination to demonstrate superior overall survival vs gem-cis and with 3-yr OS data5
26%
reduction in the risk of death with IMFINZI® + gem-cis vs gem-cis5
OVERALL SURVIVAL AT 3 YEARS (exploratory analysis)5
Adapted from Oh DY et al., 2024.5
3-year OS rates doubled with IMFINZI® + gem-cis5
This is the longest survival follow-up ever reported for a Phase III trial in this setting5
Median OS was 12.9 months (95% CI, 11.6–14.1) with IMFINZI® + gem-cis vs 11.3 months (95% CI, 10.1–12.5) with gem-cis5
* 12-month OS (95% CI) was 54.3 (48.8–59.4) in the IMFINZI® group and 47.2% (41.7–52.4) in the placebo group. 24-month OS (95% CI) was 22.9% (18.5–27.5) in the IMFINZI® group and 13.1% (9.8–17.0) in the placebo group. 36-month OS (95% CI) was 14.6% (11.0–18.6) in the IMFINZI® group and 6.9% (4.5–10.0) in the placebo group5
CI=confidence interval; cis=cisplatin; gem=gemcitabine; HR=hazard ratio; IO=immuno-oncology; OS=overall survival.
Safety and Quality of Life
Similar rates of adverse reactions with IMFINZI® + gem-cis and gem-cis4
ADVERSE REACTIONS OCCURRING IN ≥10% OF PATIENTS4
Adapted from Oh DY et al., 2022.5
Rates of Grades 3–4 adverse reactions were 75.7% with IMFINZI® + gem-cis vs 77.8% with gem-cis4
Fewer patients discontinued IMFINZI® + gem-cis due to treatment related ARs vs gem-cis: 8.9% vs 11.4%4
Median duration of study treatment was 7.3 months (range: 0.1–24.5 ) for IMFINZI® and 5.8 months (range: 0.2–21.5) for placebo.4
ALT=alanine aminotransferase; AR=adverse reaction; cis=cisplatin; gem=gemcitabine.
Dosing and administration
Start with IMFINZI® + gem-cis Q3W, followed by IMFINZI® monotherapy Q4W1
Continue with IMFINZI® for ongoing treatment without chemotherapy1
IMFINZI® is administered as a 60-minute IV infusion1
For patients with a body weight of ≥30 kg.
The recommended dose of IMFINZI® is 1500 mg in combination with chemotherapy every 3 weeks (21 days) for up to 8 cycles, followed by 1500 mg every 4 weeks as monotherapy, until disease progression or unacceptable toxicity. As chemotherapy gemcitabine 1000 mg/m2 and cisplatin 25 mg/m2 (administered on day 1 and 8) every 3 weeks (21 days) are administered for up to 8 cycles1
Patients with a body weight of ≤30 kg must receive weight-based dosing of IMFINZI® at 20 mg/kg in combination with chemotherapy dose every 3 weeks (21 days) for up to 8 cycles, followed by 20 mg/kg every 4 weeks as monotherapy until weight increases to >30 kg1
Administer IMFINZI® prior to chemotherapy when given on the same day1
Start IMFINZI® + gem-cis as clinically indicated without the need for biomarker testing
cis=cisplatin; gem=gemcitabine; IV=intravenous; Q3W=once every 3 weeks; Q4W=once every 4 weeks.
References
- IMFINZI® Information for Healthcare Professionals. www.swissmedicinfo.ch.
- Vogel, A., et al. “Biliary tract cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up.” Annals of Oncology 34.2 (2023): 127-140.
- NCCN Guidelines Biliary Tract Cancers Version 1.2024; 9 April, 2024 NCCN.org.
- Oh DY, He AR, Qin S, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer. NEJM Evidence. 2022;1(8). doi:10.1056/EVIDoa2200015 (including Supplementary Appendix and Protocol).
- 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.
- Oh DY, He AR, Qin S, et al. Updated overall survival from the Phase 3 TOPAZ-1 study of durvalumab or placebo plus gemcitabine and cisplatin in patients with advanced biliary tract cancer. Poster presented at: 2022 ESMO Congress; 9–13 September 2022; Paris, France.
- Burris HA, Okusaka T, Vogel A, et al. Durvalumab plus gemcitabine and cisplatin in advanced biliary tract cancer (TOPAZ-1): patient-reported outcomes from a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2024 May;25(5):626-635.
Professionals can request the mentioned references from AstraZeneca AG.