Gemcitabine Plus Cisplatin With or Without 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 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.

Full Title of Study: “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”

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: M7824
    • Participants after the first onset of Complete Response (CR) will receive M7824 intravenously at a dose of 2400 milligram (mg) once every 3 weeks (Q3W) until confirmed disease progression, death, unacceptable toxicity, study withdrawal, or up to 2 years.
  • Drug: Placebo
    • Participants after the first onset of CR will receive M7824 matched Placebo intravenously once every 3 weeks (Q3W) until confirmed disease progression, death, unacceptable toxicity, study withdrawal, or up to 2 year
  • 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: M7824 + Gemcitabine + Cisplatin
  • Experimental: Double-blinded Part: M7824 + 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: Progression-Free Survival (PFS) 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
  • 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 Independent Review Committee (IRC)
    • 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 Independent Review Committee (IRC)
    • 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 Independent Review Committee (IRC)
    • Time Frame: First dose of study intervention up to 4 years
  • 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
  • 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
  • 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
  • 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 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
  • 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 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 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 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 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 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
  • 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

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 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

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, service@emdgroup.com

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