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Bintrafusp Alfa Combination Therapy in Participants With Cervical Cancer (INTR@PID 046)

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04551950
Recruitment Status : Completed
First Posted : September 16, 2020
Last Update Posted : January 31, 2023
Sponsor:
Collaborator:
Merck KGaA, Darmstadt, Germany
Information provided by (Responsible Party):
EMD Serono ( EMD Serono Research & Development Institute, Inc. )

Study Description
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Brief Summary:
This study is to evaluate the safety and tolerability of bintrafusp alfa in combination with other anti-cancer therapies in participants with locally advanced or advanced cervical cancer.

Condition or disease Intervention/treatment Phase
Cervical Cancer Drug: M7824 Drug: Carboplatin Drug: Paclitaxel Drug: Bevacizumab Drug: Cisplatin Radiation: Radiotherapy Phase 1

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 25 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Safety Study of Bintrafusp Alfa in Combination With Other Anti-cancer Therapies in Participants With Locally Advanced or Advanced Cervical Cancer (INTR@PID 046)
Actual Study Start Date : October 19, 2020
Actual Primary Completion Date : June 15, 2022
Actual Study Completion Date : June 30, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Cervical Cancer

Arms and Interventions
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Arm Intervention/treatment
Experimental: Cohort 1A:M7824+cisplatin/carboplatin+paclitaxel+bevacizumab Drug: M7824
Participants will receive bintrafusp alfa until confirmed disease progression, death, unacceptable toxicity and study withdrawal maximum of 2 years (at the discretion of the Investigator).
Other Name: Bintrafusp alfa

Drug: Carboplatin
Carboplatin will be administered intravenously as per standard of care.

Drug: Paclitaxel
Paclitaxel will be administered intravenously as per standard of care.

Drug: Bevacizumab
Bevacizumab will be administrated as indicated for standard of care.

Drug: Cisplatin
Cisplatin will be administered intravenously as per standard of care.
Experimental: Cohort1B:M7824+cisplatin or carboplatin+paclitaxel Drug: M7824
Participants will receive bintrafusp alfa until confirmed disease progression, death, unacceptable toxicity and study withdrawal maximum of 2 years (at the discretion of the Investigator).
Other Name: Bintrafusp alfa

Drug: Carboplatin
Carboplatin will be administered intravenously as per standard of care.

Drug: Paclitaxel
Paclitaxel will be administered intravenously as per standard of care.

Drug: Cisplatin
Cisplatin will be administered intravenously as per standard of care.
Experimental: Cohort 2: M7824+cisplatin+ radiotherapy Drug: M7824
Participants will receive bintrafusp alfa until confirmed disease progression, death, unacceptable toxicity and study withdrawal maximum of 2 years (at the discretion of the Investigator).
Other Name: Bintrafusp alfa

Drug: Cisplatin
Cisplatin will be administered intravenously as per standard of care.

Radiation: Radiotherapy
Participants will receive radiotherapy as per standard of care.


Outcome Measures
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Primary Outcome Measures :
  1. Incidence of Dose-Limiting Toxicity (DLT) [ Time Frame: Week 1 Day 1 up to Week 4 ]
  2. Number of Participants With Adverse Events (AEs) [ Time Frame: Time from first treatment to planned final assessment at approximately 2 years ]

Secondary Outcome Measures :
  1. Concentration of Bintrafusp alfa Immediately at the End of Infusion (Ceoi) [ Time Frame: Before the first infusion up to 28 days after the last treatment, assessed up to 2 years ]
  2. Concentration of Bintrafusp alfa Immediately Before Next Dosing (Ctrough) [ Time Frame: Before the first infusion up to 28 days after the last treatment, assessed up to 2 years ]
  3. Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp alfa [ Time Frame: Before the first infusion up to 28 days after the last treatment, assessed up to 2 years ]
  4. Area Under the Serum Concentration-Time Curve From Time Zero to Last Sampling Time at Which the Concentration is at or Above the Lower Limit of Quantification (AUC0-t) of Bintrafusp alfa [ Time Frame: Before the first infusion up to 28 days after the last treatment, assessed up to 2 years ]
  5. Maximum Serum Concentration Observed (Cmax) of Bintrafusp alfa [ Time Frame: Before the first infusion up to 28 days after the last treatment, assessed up to 2 years ]
  6. Time at which Cmax Occurs (tmax) of Bintrafusp alfa [ Time Frame: Before the first infusion up to 28 days after the last treatment, assessed up to 2 years ]
  7. Elimination Half-life (t½) of Bintrafusp alfa [ Time Frame: Before the first infusion up to 28 days after the last treatment, assessed up to 2 years ]
  8. Immunogenicity of Bintrafusp alfa, as Assessed by Anti-drug Anti-body (ADA) Assay [ Time Frame: Prior to the first infusion up to 28 days after the last treatment,assessed up to 2 years ]
  9. Incidence of Dose-Limiting Toxicity (DLT) in Japanese Participants [ Time Frame: Week 1 Day 1 up to Week 4 ]
  10. Number of Japanese Participants With Adverse Events (AE) [ Time Frame: Time from first treatment to planned final assessment at approximately 2 years ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Inclusion Criteria for participants enrolling into Cohort 1:
  • Study participants have documented persistent, recurrent, or metastatic squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix
  • Study participants have not been treated with systemic chemotherapy and are not amenable to curative treatment
  • Prior radiation with or without radio-sensitizing chemotherapy is allowed
  • Inclusion Criteria for participants enrolling into Cohort 2:
  • Participants have documented evidence of cervical adenocarcinoma, squamous cell carcinoma, or adenosquamous carcinoma International Federation of Gynecology and Obstetrics (FIGO) 2018 Stages 1B2 to 4A
  • Participants have not received prior chemotherapy or radiotherapy for cervical cancer
  • Inclusion Criteria for all participants:
  • Archival tumor tissue sample or newly obtained core or excisional biopsy is required
  • Participants who have Eastern Cooperative Oncology Group (ECOG) Performance status (PS) of 0 to 1
  • Participants have a life expectancy greater than or equal to 12 weeks
  • Participants have adequate hematological, hepatic, renal and coagulation function as defined in the protocol
  • Participants with known Human immunodeficiency virus (HIV) infections are eligible if the criteria described in the protocol are met
  • Participants with Hepatitis B virus (HBV) and/or Hepatitis C virus (HCV) infections are eligible if the criteria described in the protocol are met
  • Other protocol defined inclusion criteria could apply

Exclusion Criteria:

  • Exclusion Criteria for All Participants:
  • Participants with active central nervous system (CNS) metastases causing clinical symptoms or metastases that 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 intervention
  • Participants that received any organ transplantation, including allogeneic stem-cell transplantation, but with the exception of transplants that do not require immuno-suppression
  • Participants with significant acute or chronic infections
  • Participants with active autoimmune disease that might deteriorate when receiving an immuno-stimulatory agent
  • Participants with clinically significant cardiovascular/cerebrovascular disease including: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure, or serious cardiac arrhythmia
  • Participants with history of bleeding diathesis or recent major bleeding events
  • Participant that has received prior cancer treatment with any other immunotherapy or checkpoint inhibitors or any other immune-modulating monoclonal antibody (mAb)
  • Exclusion Criteria for Participants in Cohort 1A related to use of bevacizumab:
  • Participants with inadequately controlled hypertension
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • Participants with significant vascular disease within 6 months prior to Screening
  • Participants with history of hemoptysis within 1 month prior to Screening
  • Current use of full-dose oral or parenteral anticoagulants or thrombolytic agents for therapeutic purposes
  • Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to the first dose of bevacizumab
  • Participants with a history of abdominal or trache-oesophageal fistula or gastrointestinal (GI) perforation within 6 months prior to Screening
  • Participants with clinical signs of GI obstruction or requirement for routine parenteral hydration, parenteral nutrition, or tube feeding
  • Participants with evidence of abdominal free air not explained by paracentesis or recent surgical procedure
  • Participants with serious, non-healing wound, active ulcer, or untreated bone fracture
  • Participants with proteinuria
  • Other protocol defined exclusion criteria could apply
Contacts and Locations
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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): NCT04551950


Locations
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United States, California
Stanford Health Care Hospital & Clinics
Stanford, California, United States, 94305
United States, Georgia
Augusta University - formerly Georgia Regents University
Augusta, Georgia, United States, 30912
United States, Nevada
Comprehensive Cancer Centers of Nevada
Henderson, Nevada, United States, 89074
United States, Ohio
University of Cincinnati Physicians Group, LLC - Pharmatech Oncology, Inc
Cincinnati, Ohio, United States, 45206
United States, Texas
UT Southwestern Medical Center
Dallas, Texas, United States, 75390
Japan
National Cancer Center Hospital
Chuo-ku, Japan
Saitama Medical University International Medical Center
Hidaka-shi, Japan
Cancer Institute Hospital of JFCR
Koto-ku, Japan
Osaka International Cancer Institute
Osaka-shi, Japan
Shizuoka Cancer Center
Sunto-gun, Japan
Spain
Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia
Barcelona, Spain
Hospital Universitari Vall d'Hebron - Dept of Oncology
Barcelona, Spain
ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia
Barcelona, Spain
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
More Information
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Additional Information:

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Responsible Party: EMD Serono Research & Development Institute, Inc.
ClinicalTrials.gov Identifier: NCT04551950    
Other Study ID Numbers: MS200647_0046
2020-001561-36 ( EudraCT Number )
First Posted: September 16, 2020    Key Record Dates
Last Update Posted: January 31, 2023
Last Verified: January 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
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. ):
Advanced cervical cancer
Bintrafusp alfa
M7824
 INTR@PID
Transforming growth factor-beta
Programmed death-ligand 1
Additional relevant MeSH terms:
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Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Paclitaxel
Bevacizumab
Carboplatin
Antineoplastic Agents, Phytogenic
 Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors