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

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ClinicalTrials.gov Identifier: NCT04066491
Recruitment Status : Recruiting
First Posted : August 26, 2019
Last Update Posted : July 30, 2020
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Tracking Information
First Submitted Date  ICMJE August 22, 2019
First Posted Date  ICMJE August 26, 2019
Last Update Posted Date July 30, 2020
Actual Study Start Date  ICMJE September 20, 2019
Estimated Primary Completion Date November 24, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: January 3, 2020)
  • 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 ]
Original Primary Outcome Measures  ICMJE
 (submitted: August 22, 2019)
  • 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 ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: January 3, 2020)
  • 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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: August 22, 2019)
  • 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 ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Gemcitabine Plus Cisplatin With or Without Bintrafusp Alfa (M7824) in Participants With 1L Biliary Tract Cancer (BTC)
Official Title  ICMJE 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
Brief Summary 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.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Biliary Tract Cancer
  • Cholangiocarcinoma
  • Gallbladder Cancer
Intervention  ICMJE
  • 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).
    Other Name: M7824
  • 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).
Study Arms  ICMJE
  • Experimental: Safety Run-In Part: Bintrafusp alfa + Gemcitabine + Cisplatin
    Interventions:
    • Drug: Bintrafusp alfa
    • Drug: Gemcitabine
    • Drug: Cisplatin
  • Experimental: Double-blinded Part: Bintrafusp alfa + Gemcitabine + Cisplatin
    Interventions:
    • Drug: Bintrafusp alfa
    • Drug: Gemcitabine
    • Drug: Cisplatin
  • Placebo Comparator: Double-blinded Part: Placebo + Gemcitabine + Cisplatin
    Interventions:
    • Drug: Placebo
    • Drug: Gemcitabine
    • Drug: Cisplatin
Publications * Yoo C, Oh DY, Choi HJ, Kudo M, Ueno M, Kondo S, Chen LT, Osada M, Helwig C, Dussault I, Ikeda M. Phase I study of bintrafusp alfa, a bifunctional fusion protein targeting TGF-β and PD-L1, in patients with pretreated biliary tract cancer. J Immunother Cancer. 2020 May;8(1). pii: e000564. doi: 10.1136/jitc-2020-000564.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: February 10, 2020)
512
Original Estimated Enrollment  ICMJE
 (submitted: August 22, 2019)
524
Estimated Study Completion Date  ICMJE July 24, 2023
Estimated Primary Completion Date November 24, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: US Medical Information 888-275-7376 eMediUSA@emdserono.com
Contact: Communication Center +49 6151 72 5200 service@emdgroup.com
Listed Location Countries  ICMJE Argentina,   Australia,   Chile,   Japan,   Korea, Republic of,   Poland,   Spain,   Taiwan,   United States
Removed Location Countries Germany
 
Administrative Information
NCT Number  ICMJE NCT04066491
Other Study ID Numbers  ICMJE MS200647_0055
2019-001992-35 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Per company policy, following approval of a new product or a new indication for an approved product in both the EU and the US, EMD Serono will share study protocols, anonymized patient level and study level data and redacted clinical study reports from clinical trials in patients with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website https://www.emdgroup.com/en/research/our-approach-to-research-and-development/healthcare/clinical-trials/commitment-responsible-data-sharing.html
Responsible Party EMD Serono ( EMD Serono Research & Development Institute, Inc. )
Study Sponsor  ICMJE EMD Serono Research & Development Institute, Inc.
Collaborators  ICMJE Merck KGaA, Darmstadt, Germany
Investigators  ICMJE
Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
PRS Account EMD Serono
Verification Date July 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP