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

July 31, 2023 updated by: EMD Serono Research & Development Institute, Inc.

Safety Study of Bintrafusp Alfa in Combination With Other Anti-cancer Therapies in Participants With Locally Advanced or Advanced Cervical Cancer (INTR@PID 046)

This study was 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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
25

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Japan
      • Chuo-ku, Japan
        • National Cancer Center Hospital
      • Hidaka-shi, Japan
        • Saitama Medical University International Medical Center
      • Koto-ku, Japan
        • Cancer Institute Hospital of JFCR
      • Osaka-shi, Japan
        • Osaka International Cancer Institute
      • Sunto-gun, Japan
        • Shizuoka Cancer Center
  • Spain
      • Barcelona, 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
  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford Health Care Hospital & Clinics
    • Georgia
      • Augusta, Georgia, United States, 30912
        • Augusta University - formerly Georgia Regents University
    • Nevada
      • Henderson, Nevada, United States, 89074
        • Comprehensive Cancer Centers of Nevada
    • Ohio
      • Cincinnati, Ohio, United States, 45206
        • University of Cincinnati Physicians Group, LLC - Pharmatech Oncology, Inc
    • Texas
      • Dallas, Texas, United States, 75390
        • UT Southwestern Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

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

Exclusion Criteria:

  • Exclusion Criteria for All Participants were:
  • Participants with active central nervous system (CNS) metastases causing clinical symptoms or metastases that required therapeutic intervention were excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) were not eligible unless they had fully recovered from treatment, demonstrated no progression for at least 4 weeks, and were 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 did not require immuno-suppression
  • Participants with significant acute or chronic infections
  • Participants with active autoimmune disease that might have deteriorated when receiving an immuno-stimulatory agent
  • Participants with clinically significant cardiovascular/cerebrovascular disease including: a cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure, or serious cardiac arrhythmia
  • Participants with a history of bleeding diathesis or recent major bleeding events
  • Participant that had 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 were:
  • 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 a 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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Cohort 1A:M7824+Cisplatin/Carboplatin+Paclitaxel+Bevacizumab
Drug: M7824
Participants received bintrafusp alfa until confirmed disease progression, death, unacceptable toxicity and study withdrawal maximum of 2 years (at the discretion of the Investigator).
Other Names:
  • Bintrafusp alfa
Drug: Carboplatin
Carboplatin was administered intravenously as per standard of care.
Drug: Paclitaxel
Paclitaxel was administered intravenously as per standard of care.
Drug: Bevacizumab
Bevacizumab was administrated as indicated for standard of care.
Drug: Cisplatin
Cisplatin was administered intravenously as per standard of care.
Experimental: Cohort1B:M7824+Cisplatin or Carboplatin+Paclitaxel
Drug: M7824
Participants received bintrafusp alfa until confirmed disease progression, death, unacceptable toxicity and study withdrawal maximum of 2 years (at the discretion of the Investigator).
Other Names:
  • Bintrafusp alfa
Drug: Carboplatin
Carboplatin was administered intravenously as per standard of care.
Drug: Paclitaxel
Paclitaxel was administered intravenously as per standard of care.
Drug: Cisplatin
Cisplatin was administered intravenously as per standard of care.
Experimental: Cohort 2: M7824+Cisplatin+ Radiotherapy
Drug: M7824
Participants received bintrafusp alfa until confirmed disease progression, death, unacceptable toxicity and study withdrawal maximum of 2 years (at the discretion of the Investigator).
Other Names:
  • Bintrafusp alfa
Drug: Cisplatin
Cisplatin was administered intravenously as per standard of care.
Radiation: Radiotherapy
Participants received radiotherapy as per standard of care.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Number of Participants With Dose-Limiting Toxicities (DLTs)
Time Frame: Up to 4 weeks after first administration of study intervention
DLT was defined as Adverse Events (AEs) with any of following toxicities: Grade 4 nonhematologic toxicity or hematologic toxicity lasting more than equal to (>=) 7 days despite medical intervention; Grade 3 nausea, vomiting, and diarrhea lasting >= 3 days despite supportive care; Any Grade 3 or Grade 4 nonhematologic lab value leading to hospitalization or persisting for >= 7 days; Grade 3 or Grade 4: grade 3 is defined as absolute neutrophil count (ANC) less than (<) 1,000/mm3 with a temperature of > 38.3 degree Celsius (°C); grade 4 is defined as ANC < 1,000/mm3 with a temperature of > 38.3°C, with life-threatening consequences; Thrombocytopenia < 25,000/mm3 associated with bleeding not resulting in hemodynamic instability or a life-threatening bleeding resulting in urgent intervention; Bleeding events >= Grade 3 occurring within 5 days of bintrafusp alfa treatment; Prolonged delay (> 3 weeks) in initiating Cycle 2 due to treatment-related toxicity; Grade 5 toxicity.
Up to 4 weeks after first administration of study intervention
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Time from first treatment assessed up to approximately 20 months
Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Treatment-Emergent Adverse Events (TEAEs) were defined as events with onset date or worsening during the on-treatment period. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAEs included serious TEAEs and non-serious TEAEs.
Time from first treatment assessed up to approximately 20 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa
Time Frame: Pre-dose Up to 20 months
Ceoi was the observed concentration at the end of the infusion period. This was taken directly from the observed Bintrafusp Alfa concentration-time data.
Pre-dose Up to 20 months
Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa
Time Frame: Pre-dose Up to 20 months
Ctrough was the serum concentration observed immediately before next dosing.
Pre-dose Up to 20 months
Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa
Time Frame: Pre-dose Up to 20 months
The area under the concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down).
Pre-dose Up to 20 months
Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa
Time Frame: Pre-dose Up to 20 months
AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.
Pre-dose Up to 20 months
Maximum Observed Serum Concentration (Cmax) of Bintrafusp Alfa
Time Frame: Pre-dose Up to 20 months
Cmax was obtained directly from the concentration versus time curve.
Pre-dose Up to 20 months
Time to Reach Maximum Serum Concentration (Tmax) of Bintrafusp Alfa
Time Frame: Pre-dose Up to 20 months
The time to reach the maximum observed concentration collected during a dosing interval. Tmax was obtained directly from the concentration versus time curve.
Pre-dose Up to 20 months
Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa
Time Frame: Pre-dose Up to 20 months
Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. Elimination half-life determined as 0.693/ Lamda z(λz), λz=terminal first order (elimination) rate constant.
Pre-dose Up to 20 months
Number of Participants With Positive Anti-Drug Antibody (ADA) of Bintrafusp Alfa
Time Frame: Pre-dose Up to 20 months
A validated method was applied to detect ADAs in the presence of drug in human serum. The ADA titers of positive samples were determined.
Pre-dose Up to 20 months
Number of Japanese Participants With Dose-Limiting Toxicities (DLTs)
Time Frame: Up to 4 weeks after first administration of study intervention
DLT was defined as Adverse Events (AEs) with any of following toxicities: Grade 4 nonhematologic toxicity or hematologic toxicity lasting more than equal to (>=) 7 days despite medical intervention; Grade 3 nausea, vomiting, and diarrhea lasting >= 3 days despite supportive care; Any Grade 3 or Grade 4 nonhematologic lab value leading to hospitalization or persisting for >= 7 days; Grade 3 or Grade 4: grade 3 is defined as absolute neutrophil count (ANC) less than (<) 1,000/mm3 with a temperature of > 38.3 degree Celsius (°C); grade 4 is defined as ANC < 1,000/mm3 with a temperature of > 38.3°C, with life-threatening consequences; Thrombocytopenia < 25,000/mm3 associated with bleeding not resulting in hemodynamic instability or a life-threatening bleeding resulting in urgent intervention; Bleeding events >= Grade 3 occurring within 5 days of bintrafusp alfa treatment; Prolonged delay (> 3 weeks) in initiating Cycle 2 due to treatment-related toxicity; Grade 5 toxicity.
Up to 4 weeks after first administration of study intervention
Number of Japanese Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Time Frame: Time from first treatment assessed up to approximately 20 months
Adverse Event (AE) was defined any untoward medical occurrence in a participant administered with a study drug, which does not necessarily had a causal relationship with this treatment. Treatment-Emergent Adverse Events (TEAEs) were defined as events with onset date or worsening during the on-treatment period. A serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important.
Time from first treatment assessed up to approximately 20 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
EMD Serono Research & Development Institute, Inc.

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Merck KGaA, Darmstadt, Germany

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Medical Responsible, Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
October 19, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 15, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 30, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 7, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 10, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 16, 2020

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 8, 2024

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
July 31, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
July 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • MS200647_0046
  • 2020-001561-36 (EudraCT Number)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

IPD 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

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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