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

Overview

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.

Full Title of Study: “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”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
  • Study Primary Completion Date: November 24, 2022

Interventions

  • Drug: Bintrafusp alfa
    • Participants will receive Bintrafusp alfa intravenously at a dose of 2400 milligram (mg) once every 3 weeks (Q3W) until confirmed disease progression, death, unacceptable toxicity, study withdrawal or for 2 years after the first onset of Complete Response (CR).
  • Drug: Placebo
    • Participants will receive Bintrafusp alfa matched Placebo intravenously once every 3 weeks (Q3W) until confirmed disease progression, death, unacceptable toxicity, study withdrawal or for 2 years after the first onset of CR.
  • Drug: Gemcitabine
    • Gemcitabine will be received intravenously at a dose of 1000 milligram per meter square (mg/m^2) on Day 1 and Day 8 of 21- day cycle, for 8 cycles every 3 weeks (Q3W).
  • Drug: Cisplatin
    • Cisplatin will be received intravenously at a dose of 25 mg/m^2 on Day 1 and Day 8 of 21-day cycle, for 8 cycles every 3 weeks (Q3W).

Arms, Groups and Cohorts

  • Experimental: Safety Run-In Part: Bintrafusp alfa + Gemcitabine + Cisplatin
  • Experimental: Double-blinded Part: Bintrafusp alfa + Gemcitabine + Cisplatin
  • Placebo Comparator: Double-blinded Part: Placebo + Gemcitabine + Cisplatin

Clinical Trial Outcome Measures

Primary Measures

  • 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)
  • Double-blinded Part: Overall Survival (OS)
    • Time Frame: First dose of study intervention up to 4 years

Secondary Measures

  • 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 Run-in Part: Number of Participants with Abnormalities (Grade >= 3) in Laboratory Tests
    • Time Frame: First dose of study intervention up to 4 years
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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 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 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 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 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 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
  • 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
  • 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

Participating in This Clinical Trial

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
  • 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

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • EMD Serono Research & Development Institute, Inc.
  • Collaborator
    • Merck KGaA, Darmstadt, Germany
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Medical Responsible, Study Director, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
  • Overall Contact(s)
    • US Medical Information, 888-275-7376, eMediUSA@emdserono.com

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