Clinical Trials /

Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L Biliary Tract Cancer (BTC)

NCT04066491

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) or progression-free survival (PFS) in chemotherapy and immunotherapy-naïve participants with locally advanced or metastatic BTC compared to placebo, gemcitabine and cisplatin.

Related Conditions:
  • Biliary Tract Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 2/Phase 3

Trial Eligibility

Document

Title

  • Brief Title: Gemcitabine Plus Cisplatin With or Without 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 M7824(Bintrafusp Alfa) 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

DrugSynonymsArms
M7824Bintrafusp alfaSafety Run-In Part: M7824 + Gemcitabine + Cisplatin
PlaceboDouble-blinded Part: Placebo + Gemcitabine + Cisplatin
GemcitabineSafety Run-In Part: M7824 + Gemcitabine + Cisplatin
CisplatinSafety Run-In Part: M7824 + 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 M7824 in combination with the current standard of care (SoC) (gemcitabine plus cisplatin) improves overall survival (OS) or progression-free survival (PFS) in chemotherapy and immunotherapy-naïve participants with locally advanced or metastatic BTC compared to placebo, gemcitabine and cisplatin.

Trial Arms

NameTypeDescriptionInterventions
Safety Run-In Part: M7824 + Gemcitabine + CisplatinExperimental
  • M7824
  • Gemcitabine
  • Cisplatin
Double-blinded Part: M7824 + Gemcitabine + CisplatinExperimental
  • M7824
  • Gemcitabine
  • Cisplatin
Double-blinded Part: Placebo + Gemcitabine + CisplatinPlacebo 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 verified independently by IRC

          -  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

          -  Active autoimmune disease that might deteriorate when receiving an immunostimulatory
             agent

          -  History of or concurrent interstitial lung disease

          -  History of hypersensitivity reactions to M7824, 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 Independent Review Committee (IRC)
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 Independent Review Committee (IRC)
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 Independent Review Committee (IRC)
Time Frame:First dose of study intervention up to 4 years
Safety Issue:
Description:
Measure:Double-blinded Part: Objective Response (OR) 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) 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: 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:
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 M7824
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 M7824
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 M7824
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 M7824
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 M7824
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 M7824
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 M7824
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:

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

Last Updated

November 14, 2019