M7824 Monotherapy in Locally Advanced or Metastatic Second Line (2L) Biliary Tract Cancer (Cholangiocarcinoma and Gallbladder Cancer)

NCT03833661 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: MS200647_00472018-003707-19
• Study Type: interventional
• Target: 159
• Locations: 9 countries
• Sites: 33

Brief Summary

The study to evaluate M7824 monotherapy in participants with advanced or metastatic biliary tract cancer (BTC) who failed or were intolerant to first-line (1L) chemotherapy.

Conditions

Biliary Tract Cancer; Cholangiocarcinoma; Gallbladder Cancer

Keywords

M7824; Bintrafusp alfa (proposed INN); Transforming growth factor-beta; First-line Platinum-Based Chemotherapy; Programmed death-ligand 1; Metastatic Biliary Tract Cancer; Cholangiocarcinoma; Gallbladder cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

  Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by IRC.

  Time from first treatment up to 555 days

Secondary Outcomes (18)

• Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

  Time from first documentation of objective response to data cutoff (assessed up to 736 days)

• Durable Response Rate (DRR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

  Time from first treatment to data cutoff (assessed up to 736 days)

• Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs)

  Time from first treatment to data cutoff (assessed up to 736 days)

• Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)

  Time from first administration of study drug until the first documentation of PD or death, assessed up to data-cutoff (736 days)

• Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator

  Time from first treatment to data cutoff (assessed up to 736 days)

Study Arms (1)

M7824

EXPERIMENTAL

Drug: M7824

Interventions

M7824 DRUG

Participants received an intravenous infusion of 1200 milligrams (mg) M7824 once every 2 weeks until confirmed disease progression, death, unacceptable toxicity or study withdrawal.

Also known as: Bintrafusp alfa

M7824

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are participants with histologically or cytologically confirmed locally advanced or metastatic BTC.
• Availability of tumor (primary or metastatic) archival material or fresh biopsies is mandatory
• Participants with BTC must have failed or be intolerant to 1L systemic platinum-based chemotherapy administered for locally advanced or metastatic disease. Only one prior treatment line is allowed
• Disease must be measurable with at least 1 unidimensionally measurable lesion by RECIST 1.1
• Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) of 0 to 1
• Life expectancy \>= 12 weeks as judged by the Investigator
• Adequate hematological function defined by white blood cell (WBC) count \>= 3 \* 10\^9/Litre with absolute neutrophil count (ANC) \>= 1.5 \* 109/Litre, lymphocyte count \>= 0.5 \* 10\^9/Litre, platelet count \>=75 \* 10\^9/Litre, and hemoglobin (Hgb) \>= 9 grams/decilitre
• Adequate hepatic function defined by a total bilirubin level =\< 1.5 \* upper limit of normal (ULN), an aspartate aminotransferase (AST) level =\< 2.5 \* ULN, and an alanine aminotransferase (ALT) level =\<2.5 \* ULN. For participants with liver involvement in their tumor, AST =\< 5.0 \* ULN and ALT =\< 5.0 \* ULN is acceptable
• Adequate coagulation function defined as prothrombin time (PT) or international normalized ratio (INR) =\< 1.5 \* ULN unless the participant is receiving anticoagulant therapy
• Albumin \>= 3.0 grams/decilitre
• Hepatitis B virus (HBV) deoxyribonucleic acid (DNA) positive participants must be treated and on a stable dose of antivirals
• Adequate renal function defined by either creatinine =\< 1.5 \* ULN or an estimated creatinine clearance (CCr) \> 40 milliliter (mL) per minute (min) according to the Cockcroft-Gault formula or by measure of CCr from 24-hour urine collection

You may not qualify if:

• Ampullary cancer was excluded
• Significant acute or chronic infections
• Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
• Interstitial lung disease or its history
• Participants who were not eligible for or have not been treated with 1L systemic chemotherapy
• Anticancer treatment within 21 days before the start of study intervention
• Concurrent treatment with nonpermitted drugs
• Prior participation in a M7824 clinical trial
• Prior therapy with other immunotherapy or checkpoint inhibitors, such as anti-PD 1, anti PD L1, anti- cytotoxic T-cell lymphocyte-4 (CTLA-4) antibodies.
• Pregnancy or breast feeding
• Systemic anticancer treatment after failing 1L platinum-based chemotherapy

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (33)

Mayo Clinic Arizona

Scottsdale, Arizona, 85259, United States

Location

UCSF Mount Zion Medical Ctr

San Francisco, California, 94158, United States

Location

Mayo Clinic in Florida - Department of Neurology

Jacksonville, Florida, 32224, United States

Location

H. Lee Moffitt Cancer Center and Research Institute, Inc

Tampa, Florida, 33612-9497, United States

Location

Sidney Kimmel Comprehensive Cancer Center at John Hopkins

Baltimore, Maryland, 21231, United States

Location

Mayo Clinic - Rochester

Rochester, Minnesota, 55905, United States

Location

MD Anderson Cancer Center - Unit

Houston, Texas, 77030, United States

Location

Peking University Cancer Hospital

Beijing, 100142, China

Location

Affiliated Tumor Hospital of Harbin Medical University

Harbin, 150081, China

Location

Groupe Hospitalier Sud - Hôpital Haut Lévêque - Service Hepato Gastroentérologie Oncologie Digest

Pessac, 33604, France

Location

ICO - Site René Gauducheau

Saint-Herblain, 44805, France

Location

Institut Gustave Roussy

Villejuif, 94805, France

Location

Istituto Clinico Humanitas

Rozzano, Milano, 20089, Italy

Location

Azienda Ospedaliera Universitaria Policlinico Sant'Orsola Malpighi - Unita' Operativa di Pediatria

Bologna, 40138, Italy

Location

Fondazione IRCCS Istituto Nazionale dei Tumori Milano

Milan, 20133, Italy

Location

Policlinico Universitario Agostino Gemelli - UOC Oncologia Medica

Roma, 00168, Italy

Location

National Cancer Center Hospital - Dept of Hepatobiliary and Pancreatic Oncology

Chūōku, 104-0045, Japan

Location

National Cancer Center Hospital East

Kashiwa-shi, 277-8577, Japan

Location

Kyorin University Hospital - Dept of Oncology

Mitaka-shi, 181-8611, Japan

Location

Kindai University Hospital - Dept of Gastroenterology

Osakasayama-shi, 589-8511, Japan

Location

Kanagawa Cancer Center

Yokohama, 241-8515, Japan

Location

Seoul National University Bundang Hospital

Seongnam-si, 13620, South Korea

Location

Seoul National University Hospital

Seoul, 03080, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, 03722, South Korea

Location

Asan Medical Center

Seoul, 05505, South Korea

Location

Samsung Medical Center

Seoul, 135-710, South Korea

Location

Hospital de la Santa Creu i Sant Pau

Barcelona, 08027, Spain

Location

Hospital Universitari Vall d'Hebron - Dept of Oncology

Barcelona, 8035, Spain

Location

Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia

Madrid, 28050, Spain

Location

Chang Gung Memorial Hospital, Linkou

Linkou District, 333, Taiwan

Location

National Cheng Kung University Hospital

Tainan, 704, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

St James's University Hospital - Dept of Oncology

Leeds, LS9 7TF, United Kingdom

Location

Related Publications (3)

• 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-beta and PD-L1, in patients with pretreated biliary tract cancer. J Immunother Cancer. 2020 May;8(1):e000564. doi: 10.1136/jitc-2020-000564.

  PMID: 32461347 RESULT

• Milenkovic-Grisic AM, Terranova N, Mould DR, Vugmeyster Y, Mrowiec T, Machl A, Girard P, Venkatakrishnan K, Khandelwal A. Tumor growth inhibition modeling in patients with second line biliary tract cancer and first line non-small cell lung cancer based on bintrafusp alfa trials. CPT Pharmacometrics Syst Pharmacol. 2024 Jan;13(1):143-153. doi: 10.1002/psp4.13068. Epub 2023 Dec 13.

  PMID: 38087967 DERIVED

• Yoo C, Javle MM, Verdaguer Mata H, de Braud F, Trojan J, Raoul JL, Kim JW, Ueno M, Lee CK, Hijioka S, Cubillo A, Furuse J, Azad N, Sato M, Vugmeyster Y, Machl A, Bajars M, Bridgewater J, Oh DY, Borad MJ. Phase 2 trial of bintrafusp alfa as second-line therapy for patients with locally advanced/metastatic biliary tract cancers. Hepatology. 2023 Sep 1;78(3):758-770. doi: 10.1097/HEP.0000000000000365. Epub 2023 Apr 1.

  PMID: 36999533 DERIVED

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Biliary Tract Neoplasms; Cholangiocarcinoma; Gallbladder Neoplasms; Camurati-Engelmann Syndrome

Interventions

bintrafusp alfa protein, human

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Biliary Tract Diseases; Digestive System Diseases; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Gallbladder Diseases; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 6, 2019
• First Posted: February 7, 2019
• Study Start: March 26, 2019
• Primary Completion: November 9, 2020
• Study Completion: September 30, 2022
• Last Updated: October 25, 2023
• Results First Posted: January 10, 2022

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR, ANALYTIC CODE
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.

Locations

ES (3); CN (2); FR (3); IT (4); JP (5); GB (1); TW (3); KR (5); US (7)