Bintrafusp Alfa Monotherapy in Platinum-Experienced Cervical Cancer

NCT04246489 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: MS200647_00172019-003583-40
• Study Type: interventional
• Target: 146
• Locations: 12 countries
• Sites: 73

Brief Summary

The main purpose of this study was to evaluate clinical efficacy and safety of bintrafusp alfa in participants with advanced, unresectable cervical cancer with disease progression during or after platinum-containing chemotherapy.

Conditions

Uterine Cervical Neoplasms

Keywords

M7824; INTR@PID; Bintrafusp alfa; programmed death-ligand 1; Cervical Cancer; Transforming growth factor-β (TGF-β)

Outcome Measures

Primary Outcomes (1)

• Number 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 number 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 688 days

Secondary Outcomes (12)

• 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 treatment up to 688 days

• Durable Response 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 up to 688 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 up to 688 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 688 days

• Number 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 up to 688 days

Study Arms (1)

Bintrafusp alfa

EXPERIMENTAL

Drug: Bintrafusp alfa

Interventions

Bintrafusp alfa DRUG

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

Also known as: M7824

Bintrafusp alfa

Eligibility Criteria

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

You may qualify if:

• Participants who had advanced unresectable and/or metastatic cervical cancer (squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma) with disease progression during or after the prior platinum-containing chemotherapy:
• The prior platinum-containing chemotherapy may be a systemic treatment for advanced unresectable, recurrent, persistent or metastatic disease or treatment in the adjuvant or neo-adjuvant setting with disease progression or recurrence within 6 months of completion of platinum-containing chemotherapy
• Participants who previously only received platinum as a radiosensitizer are not eligible
• Participants must be naïve to checkpoint inhibitors
• Participants who had measurable disease
• Participants who provide a tumor tissue sample, either from archival tissue or newly obtained core or excisional biopsy. If the participant received local therapy (For example: radiation therapy or chemoradiotherapy) after the archival tissue was taken, a new biopsy was required
• Participants who had Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1
• Life expectancy greater than or equals to (\>=) 12 weeks as judged by the Investigator
• Adequate hematological, hepatic and renal function as defined in the protocol
• Participants with known Human Immunodeficiency Virus (HIV) infections were in general eligible if the following criteria are met:
• Clinically indicated participants must be stable on antiretroviral therapy (ART) for at least 4 weeks and agree to adhere to ART
• had no evidence of documented multi-drug resistance that would prevent effective ART
• had an HIV viral load of \< 400 copies per milliliter (/mL) at Screening
• had CD4+ T-cell (CD4+) counts \>= 350 cells/microliter
• For participants with a history of an Acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the last 12 months, participants may be eligible only after consultation and agreement with the study Medical Monitor

You may not qualify if:

• Participants with active central nervous system (CNS) metastases causing clinical symptoms or require therapeutic intervention are excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 4 weeks, and are not using steroids for at least 7 days prior to the start of study treatment
• Participants with interstitial lung disease or has had a history of pneumonitis that has required oral or intravenous (IV) steroids
• Participants with significant acute or chronic infections
• Participants with active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
• Participants with clinically significant cardiovascular/cerebrovascular disease including: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure, or serious cardiac arrhythmia

Sponsors & Collaborators

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

Study Sites (73)

Highlands Oncology Group

Fayetteville, Arkansas, 72703, United States

Location

University of Arkansas Medical Sciences

Little Rock, Arkansas, 72202-3500, United States

Location

Stanford University Hospital and Clinics - Stanford Cancer Center

Stanford, California, 94305, United States

Location

The Stamford Hospital

Stamford, Connecticut, 06902, United States

Location

Karmanos Cancer Institute

Farmington Hills, Michigan, 48334, United States

Location

Washington University in St. Louis

St Louis, Missouri, 63110, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89074, United States

Location

UC Health Clinical Trials Office

Cincinnati, Ohio, 45229, United States

Location

Oregon Health &amp; Science University

Portland, Oregon, 97229, United States

Location

The West Clinic

Germantown, Tennessee, 38138, United States

Location

SCRI - Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

Centro Oncologico Riojano Integral (CORI)

La Rioja, Argentina

Location

Sanatorio El Parque

Salta, Argentina

Location

Centro Medico San Roque S.R.L.

San Miguel de Tucumán, Argentina

Location

Peter MacCallum Cancer Centre-East Melbourne

Melbourne, Australia

Location

Linear Clinical Research Limited

Nedlands, Australia

Location

Calvary Mater Newcastle

Waratah, Australia

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Institut Jules Bordet

Brussels, Belgium

Location

Universitair Ziekenhuis Gent - Pneumology

Ghent, Belgium

Location

AZ Groeninge - Campus Kennedylaan - account 2

Kortrijk, Belgium

Location

CHU de Liège - PARENT

Liège, Belgium

Location

CHU Sart Tilman

Liège, Belgium

Location

UZ Leuven

Pellenberg, Belgium

Location

GZA Ziekenhuizen - Campus Sint-Augustinus

Wilrijk, Belgium

Location

HGB - Hospital Giovanni Battista - Mãe de Deus Center - Centro de Pesquisa Clínica - Instituto do Câncer

Porto Alegre, Brazil

Location

Clínica de Pesquisas e Centro de Estudos em Oncologia Ginecológica e Mamária Ltda.

São Paulo, Brazil

Location

IBCC - Instituto Brasileiro de Controle do Câncer

São Paulo, Brazil

Location

Chongqing Cancer Hospital

Chongqing, China

Location

Sun Yat-sen University, Cancer Center

Guangzhou, China

Location

Zhejiang Cancer Hospital

Hangzhou, China

Location

Anhui Provincial Hospital

Hefei, China

Location

Shanghai Cancer Hospital, Fudan University

Shanghai, China

Location

Union Hospital Tongji Medical College Huazhong University of Science and Technology

Wuhan, China

Location

Henan Cancer Hospital

Zhengzhou, China

Location

Institut Bergonié

Bordeaux, France

Location

Centre Oscar lambret - Service d'Oncologie medicale

Lille, France

Location

Centre Léon Bérard

Lyon, France

Location

Centre Antoine Lacassagne

Nice, France

Location

Hôpital Cochin - Hematologie et Oncologie Médicale

Paris, France

Location

Centre Hospitalier Lyon Sud - service d'oncologie medicale

Pierre-Bénite, France

Location

CARIO - Centre Armoricain de Radiothérapie, Imagerie médicale et Oncologie

Plérin, France

Location

Institut Jean Godinot - Service d'hématologie et Oncologie Médicale

Reims, France

Location

ICO - Site René Gauducheau

Saint-Herblain, France

Location

Institut de Cancérologie de Strasbourg Europe - ICANS - Service d'oncologie médicale

Strasbourg, France

Location

Orszagos Onkologiai Intezet - Nogyogyaszati Osztaly

Budapest, Hungary

Location

SzSzB Megyei Korhazak es Egyetemi Oktatokorhaz - Onkoradiologia

Nyíregyháza, Hungary

Location

National Cancer Center Hospital - Dept of Mammary Gland/Oncology

Chūōku, Japan

Location

NHO Kyushu Cancer Center - Dept of Gynecology

Fukuoka, Japan

Location

Saitama Medical University International Medical Center - Dept of Gynecology/Oncology

Hidaka-shi, Japan

Location

Cancer Institute Hospital of JFCR - Dept of Gynecology

Kōtoku, Japan

Location

Kurume University Hospital - Dept of Gynecology

Kurume-shi, Japan

Location

Jikei University Hospital - Dept of Gynecology

Minatoku, Japan

Location

University Hospital, University of the Ryukyus - Dept of Obstetrics/Gynecology

Nakagami-gun, Japan

Location

Osaka International Cancer Institute - Dept of Gynecology

Osaka, Japan

Location

NHO Hokkaido Cancer Center - Dept of Gynecology

Sapporo, Japan

Location

Kanagawa Cancer Center - Dept of Gynecology

Yokohama, Japan

Location

BHI of Omsk region "Clinical Oncology Dispensary"

Omsk, Russia

Location

LLC "ClinicaUZI4D"

Pyatigorsk, Russia

Location

National Cancer Center

Goyang-si, South Korea

Location

Asan Medical Center

Seoul, South Korea

Location

Samsung Medical Center

Seoul, South Korea

Location

Seoul National University Hospital

Seoul, South Korea

Location

Severance Hospital, Yonsei University Health System

Seoul, South Korea

Location

Ajou University Hospital

Suwon, South Korea

Location

Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron - Dept of Oncology

Barcelona, Spain

Location

ICO Girona - Hospital Doctor Josep Trueta - Servicio de Oncologia Medica

Girona, Spain

Location

Clinica Universidad de Navarra (MAD) - Oncology Service

Madrid, Spain

Location

Hospital Universitario 12 de Octubre - Servicio de Oncologia

Madrid, Spain

Location

Hospital Universitario Ramon y Cajal - Servicio de Oncologia

Madrid, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, Spain

Location

Hospital Clinico Universitario de Valencia - Servicio de Hematologia y Oncologia Medica

Valencia, Spain

Location

Related Publications (4)

• Strauss J, Heery CR, Schlom J, Madan RA, Cao L, Kang Z, Lamping E, Marte JL, Donahue RN, Grenga I, Cordes L, Christensen O, Mahnke L, Helwig C, Gulley JL. Phase I Trial of M7824 (MSB0011359C), a Bifunctional Fusion Protein Targeting PD-L1 and TGFbeta, in Advanced Solid Tumors. Clin Cancer Res. 2018 Mar 15;24(6):1287-1295. doi: 10.1158/1078-0432.CCR-17-2653. Epub 2018 Jan 3.

  PMID: 29298798 BACKGROUND

• Lan Y, Zhang D, Xu C, Hance KW, Marelli B, Qi J, Yu H, Qin G, Sircar A, Hernandez VM, Jenkins MH, Fontana RE, Deshpande A, Locke G, Sabzevari H, Radvanyi L, Lo KM. Enhanced preclinical antitumor activity of M7824, a bifunctional fusion protein simultaneously targeting PD-L1 and TGF-beta. Sci Transl Med. 2018 Jan 17;10(424):eaan5488. doi: 10.1126/scitranslmed.aan5488.

  PMID: 29343622 BACKGROUND

• Vugmeyster Y, Grisic AM, Wilkins JJ, Loos AH, Hallwachs R, Osada M, Venkatakrishnan K, Khandelwal A. Model-informed approach for risk management of bleeding toxicities for bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1. Cancer Chemother Pharmacol. 2022 Oct;90(4):369-379. doi: 10.1007/s00280-022-04468-6. Epub 2022 Sep 6.

  PMID: 36066618 BACKGROUND

• Birrer M, Li G, Yunokawa M, Lee JY, Kim BG, Oppermann CP, Zhou Q, Nishio S, Okamoto A, Wu X, Mileshkin L, Oaknin A, Ray-Coquard I, Hasegawa K, Jehl G, Vugmeyster Y, Zhang S, Bajars M, Yonemori K. Bintrafusp Alfa for Recurrent or Metastatic Cervical Cancer After Platinum Failure: A Nonrandomized Controlled Trial. JAMA Oncol. 2024 Sep 1;10(9):1204-1211. doi: 10.1001/jamaoncol.2024.2145.

  PMID: 39052242 DERIVED

Related Links

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

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

bintrafusp alfa protein, human

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

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: January 28, 2020
• First Posted: January 29, 2020
• Study Start: March 30, 2020
• Primary Completion: April 5, 2022
• Study Completion: December 14, 2022
• Last Updated: October 23, 2023
• Results First Posted: May 9, 2023

Record last verified: 2023-09

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

BR (3); CN (7); HU (2); ES (8); AU (3); JP (10); RU (2); US (11); FR (10); KR (6); AR (3); BE (8)