Description:
Study consists of an open-label, safety run-in part and a randomized, double-blind,
placebo-controlled Phase 2/3 part. In the Phase 2/3 part, the study will evaluate whether
bintrafusp alfa in combination with the current standard of care (SoC) (gemcitabine plus
cisplatin) improves overall survival (OS) in chemotherapy and immunotherapy-naïve
participants with locally advanced or metastatic BTC compared to placebo, gemcitabine and
cisplatin.
Title
- Brief Title: Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L Biliary Tract Cancer (BTC)
- Official Title: A Phase II/III, Multicenter, Randomized, Placebo-controlled Study of Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) as First-line Treatment of Biliary Tract Cancer
Clinical Trial IDs
- ORG STUDY ID:
MS200647_0055
- SECONDARY ID:
2019-001992-35
- NCT ID:
NCT04066491
Conditions
- Biliary Tract Cancer
- Cholangiocarcinoma
- Gallbladder Cancer
Interventions
Drug | Synonyms | Arms |
---|
Bintrafusp alfa | M7824 | Double-blinded Part: Bintrafusp alfa + Gemcitabine + Cisplatin |
Placebo | | Double-blinded Part: Placebo + Gemcitabine + Cisplatin |
Gemcitabine | | Double-blinded Part: Bintrafusp alfa + Gemcitabine + Cisplatin |
Cisplatin | | Double-blinded Part: Bintrafusp alfa + Gemcitabine + Cisplatin |
Purpose
Study consists of an open-label, safety run-in part and a randomized, double-blind,
placebo-controlled Phase 2/3 part. In the Phase 2/3 part, the study will evaluate whether
bintrafusp alfa in combination with the current standard of care (SoC) (gemcitabine plus
cisplatin) improves overall survival (OS) in chemotherapy and immunotherapy-naïve
participants with locally advanced or metastatic BTC compared to placebo, gemcitabine and
cisplatin.
Trial Arms
Name | Type | Description | Interventions |
---|
Safety Run-In Part: Bintrafusp alfa + Gemcitabine + Cisplatin | Experimental | | - Bintrafusp alfa
- Gemcitabine
- Cisplatin
|
Double-blinded Part: Bintrafusp alfa + Gemcitabine + Cisplatin | Experimental | | - Bintrafusp alfa
- Gemcitabine
- Cisplatin
|
Double-blinded Part: Placebo + Gemcitabine + Cisplatin | Placebo Comparator | | - Placebo
- Gemcitabine
- Cisplatin
|
Eligibility Criteria
Inclusion Criteria:
- Are participants with histologically or cytologically confirmed locally advanced or
metastatic BTC
- Participants must have available tumor tissue (primary or metastatic) (archival or
fresh biopsies) before the first administration of study treatment
- At least 1 measurable lesion according to RECIST 1.1
- Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1 at study
entry and at Week 1, Day 1 prior to dosing
- Life expectancy of >= 12 weeks, as judged by the Investigator
- Adequate hematological function, hepatic function, renal function, coagulation
function as defined in the protocol
- Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be
treated and on a stable dose of antivirals
- Other protocol defined inclusion criteria could apply
Exclusion Criteria:
- Previous and/or intercurrent cancers
- Receipt of any organ transplantation, including allogeneic stem-cell transplantation,
but with the exception of transplants that do not require immunosuppression
- Participants with symptomatic central nervous system (CNS) metastases
- Significant acute or chronic infection including known history of positive test for
human immunodeficiency virus (HIV), active tuberculosis, uncontrolled biliary
infection and active bacterial or fungal infection requiring systemic therapy (with
the exception of hepatitis B and hepatitis C) requiring systemic therapy at study
entry and at Week 1 Day 1 prior to dosing.
- Active autoimmune disease that might deteriorate when receiving an immunostimulatory
agent
- History of or concurrent interstitial lung disease
- History of hypersensitivity reactions to bintrafusp alfa, anaphylaxis, or recent
(within 5 months) uncontrolled asthma, cardiovascular/cerebrovascular disease
- Chronic obstructive pulmonary disease exacerbation or other respiratory illness
requiring hospitalization or precluding study therapy within 30 days before
randomization
- Prior therapy with any antibody/drug targeting T-cell coregulatory proteins (immune
checkpoints)
- Other protocol defined exclusion criteria could apply
Maximum Eligible Age: | N/A |
Minimum Eligible Age: | 18 Years |
Eligible Gender: | All |
Healthy Volunteers: | No |
Primary Outcome Measures
Measure: | Safety Run-in Part: Number of Participants with Dose-Limiting Toxicities (DLTs) During the DLT Evaluation Period |
Time Frame: | Day 1 up to Day 21 of Cycle 1 (each Cycle is of 21 days) |
Safety Issue: | |
Description: | |
Secondary Outcome Measures
Measure: | Safety Run-in Part: Number of Participants with Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related Adverse Events |
Time Frame: | First dose of study intervention up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Safety Run-in Part: Number of Participants with Abnormalities (Grade >= 3) in Laboratory Tests |
Time Frame: | First dose of study intervention up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Double-blinded: Confirmed Objective Response (COR) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Assessed by Investigator |
Time Frame: | First dose of study intervention up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Double-blinded Part: Duration of Response (DOR) Assessed From Complete Response (CR) or Partial Response (PR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator or Death |
Time Frame: | Time from CR or PR up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Double-blinded Part: Durable Response of at Least 6 Months According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 as Assessed by Investigator |
Time Frame: | First dose of study intervention up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Double-blinded Part: Number of Participants with Treatment-Emergent Adverse Events (TEAEs), Treatment Related Adverse Events and Adverse Events of Special Interest (AESI) |
Time Frame: | First dose of study intervention up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Double-blinded Part: Serum Concentration Observed Immediately at the End of Infusion (Ceoi) of Bintrafusp alfa |
Time Frame: | Pre-dose, 30 minutes post-dose at Week 1 Day 1, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Double-blinded Part: Serum Concentration Observed Immediately Before Next Dosing (Ctrough) of Bintrafusp alfa |
Time Frame: | Pre-dose, 30 minutes post-dose at Week 1 Day 1, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Safety Run-in Part: Area Under Serum Concentration-Time Curve (AUC0-t) From Time Zero to The Last Sampling Time of Bintrafusp alfa |
Time Frame: | Pre-dose, 30 minutes post-dose at Week 1 Day 1 and Day 2, Week 2 Day 8, Week 3 Day 15, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Safety Run-in Part: Area Under Serum Concentration-Time Curve from Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp alfa |
Time Frame: | Pre-dose, 30 minutes post-dose at Week 1 Day 1 and Day 2, Week 2 Day 8, Week 3 Day 15, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Safety Run-in Part: Maximum Observed Serum Concentration (Cmax) of Bintrafusp alfa |
Time Frame: | Pre-dose, 30 minutes post-dose at Week 1 Day 1 and Day 2, Week 2 Day 8, Week 3 Day 15, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Safety Run-in Part: Time to Reach Maximum Observed Serum Concentration (Tmax) of Bintrafusp alfa |
Time Frame: | Pre-dose, 30 minutes post-dose at Week 1 Day 1 and Day 2, Week 2 Day 8, Week 3 Day 15, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Safety Run-in Part: Apparent Terminal Half-Life (t1/2) of Bintrafusp alfa |
Time Frame: | Pre-dose, 30 minutes post-dose at Week 1 Day 1 and Day 2, Week 2 Day 8, Week 3 Day 15, Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Double-blinded Part: Immunogenicity as measured by Anti-drug Antibodies Concentration |
Time Frame: | Pre-dose, 30 minutes post-dose at Week 4 Day 22, Week 7 Day 43, Week 13 Day 85, Week 19 Day 127, Week 25 Day 169 and every 12 week from Week 25 approximately up to 4 years |
Safety Issue: | |
Description: | |
Measure: | Double-blinded Part: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 Assessed by Investigator |
Time Frame: | First dose of study intervention up to 4 years |
Safety Issue: | |
Description: | |
Details
Phase: | Phase 2/Phase 3 |
Primary Purpose: | Interventional |
Overall Status: | Recruiting |
Lead Sponsor: | EMD Serono Research & Development Institute, Inc. |
Trial Keywords
- Metastatic Biliary Tract Cancer
- Cholangiocarcinoma
- Gallbladder Cancer
- Ampullary cancer
- M7824
- Bintrafusp alfa
- Transforming growth factor-beta
- Programmed death-ligand 1
- INTR@PID
Last Updated
April 27, 2021