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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04066491
Recruitment Status : Recruiting
First Posted : August 26, 2019
Last Update Posted : January 7, 2020
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

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

Condition or disease Intervention/treatment Phase
Biliary Tract Cancer Cholangiocarcinoma Gallbladder Cancer Drug: Bintrafusp alfa Drug: Placebo Drug: Gemcitabine Drug: Cisplatin Phase 2 Phase 3

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 524 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : September 20, 2019
Estimated Primary Completion Date : November 24, 2022
Estimated Study Completion Date : July 24, 2023


Arm Intervention/treatment
Experimental: Safety Run-In Part: Bintrafusp alfa + Gemcitabine + Cisplatin Drug: Bintrafusp alfa
Participants after the first onset of Complete Response (CR) 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.
Other Name: M7824

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).

Experimental: Double-blinded Part: Bintrafusp alfa + Gemcitabine + Cisplatin Drug: Bintrafusp alfa
Participants after the first onset of Complete Response (CR) 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.
Other Name: M7824

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).

Placebo Comparator: Double-blinded Part: Placebo + Gemcitabine + Cisplatin Drug: Placebo
Participants after the first onset of CR will receive Bintrafusp alfa matched Placebo intravenously once every 3 weeks (Q3W) until confirmed disease progression, death, unacceptable toxicity, study withdrawal.

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).




Primary Outcome Measures :
  1. 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) ]
  2. Double-blinded Part: Overall Survival (OS) [ Time Frame: First dose of study intervention up to 4 years ]

Secondary Outcome Measures :
  1. 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 ]
  2. 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 ]
  3. 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 ]
  4. 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 ]
  5. 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 ]
  6. 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 ]
  7. 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 ]
  8. 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 ]
  9. 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 ]
  10. 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 ]
  11. 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 ]
  12. 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 ]
  13. 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 ]
  14. 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 ]
  15. 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 ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  • 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04066491


Contacts
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Contact: US Medical Information 888-275-7376 service@emdgroup.com
Contact: Communication Center +49 6151 72 5200 service@emdgroup.com

Locations
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Japan
Aichi Cancer Center Hospital Recruiting
Nagoya-shi, Aichi-Ken, Japan, 464-8681
Contact: Takamichi Kuwahara    +81527626111    kuwa_tak@aichi-cc.jp   
Chiba Cancer Center Recruiting
Chiba-shi, Chiba-Ken, Japan
Contact: Kentaro Sudo    +81432645431    ksudo@chiba-cc.jp   
National Cancer Center Hospital East Recruiting
Kashiwa-shi, Chiba-Ken, Japan, 277-8577
Contact: Masafumi Ikeda    +81471331111    masikeda@east.ncc.go.jp   
NHO Kyushu Cancer Center Not yet recruiting
Fukuoka-shi, Fukuoka-Ken, Japan, 811-1395
Contact: Masayuki Furukawa    +81925413231    massfullfuru@yahoo.co.jp   
Kanagawa Cancer Center Recruiting
Yokohama-shi, Kanagawa-Ken, Japan
Contact: Makoto Ueno    +81455202222    uenom@kcch.jp   
Kindai University Hospital Recruiting
Osakasayama-shi, Osaka-Fu, Japan, 589-8511
Contact: Masatoshi Kudo    +81723660221    m-kudo@med.kindai.ac.jp   
National Cancer Center Hospital Recruiting
Chuo-ku, Tokyo-To, Japan
Contact: Chigusa Morizane    +81335422511    cmorizan@ncc.go.jp   
Kyorin University Hospital Not yet recruiting
Mitaka-shi, Tokyo-To, Japan, 181-8611
Contact: Junji Furuse    +81422475511    jfuruse@ks.kyorin-u.ac.jp   
Sponsors and Collaborators
EMD Serono Research & Development Institute, Inc.
Merck KGaA, Darmstadt, Germany
Investigators
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Study Director: Medical Responsible Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Additional Information:
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Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT04066491    
Other Study ID Numbers: MS200647_0055
2019-001992-35 ( EudraCT Number )
First Posted: August 26, 2019    Key Record Dates
Last Update Posted: January 7, 2020
Last Verified: December 2019
Individual Participant Data (IPD) Sharing Statement:
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

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by EMD Serono ( EMD Serono Research & Development Institute, Inc. ):
Metastatic Biliary Tract Cancer
Cholangiocarcinoma
Gallbladder Cancer
Ampullary cancer
M7824
Bintrafusp alfa
Transforming growth factor-beta
Programmed death-ligand 1
Additional relevant MeSH terms:
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Biliary Tract Neoplasms
Gallbladder Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Gallbladder Diseases
Cholangiocarcinoma
Adenocarcinoma
Carcinoma
Biliary Tract Diseases
Digestive System Diseases
Gemcitabine
Cisplatin
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs