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

Primary Purpose

Cervical Cancer

Status
Completed
Phase
Phase 1
Locations
International
Study Type
Interventional
Intervention
M7824
Carboplatin
Paclitaxel
Bevacizumab
Cisplatin
Radiotherapy
Sponsored by
EMD Serono Research & Development Institute, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Cervical Cancer focused on measuring Advanced cervical cancer, Bintrafusp alfa, M7824, INTR@PID, Transforming growth factor-beta, Programmed death-ligand 1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Stanford Health Care Hospital & Clinics
  • Augusta University - formerly Georgia Regents University
  • Comprehensive Cancer Centers of Nevada
  • University of Cincinnati Physicians Group, LLC - Pharmatech Oncology, Inc
  • UT Southwestern Medical Center
  • National Cancer Center Hospital
  • Saitama Medical University International Medical Center
  • Cancer Institute Hospital of JFCR
  • Osaka International Cancer Institute
  • Shizuoka Cancer Center
  • Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia
  • Hospital Universitari Vall d'Hebron - Dept of Oncology
  • ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Cohort 1A:M7824+cisplatin/carboplatin+paclitaxel+bevacizumab

Cohort1B:M7824+cisplatin or carboplatin+paclitaxel

Cohort 2: M7824+cisplatin+ radiotherapy

Arm Description

Outcomes

Primary Outcome Measures

Incidence of Dose-Limiting Toxicity (DLT)
Number of Participants With Adverse Events (AEs)

Secondary Outcome Measures

Concentration of Bintrafusp alfa Immediately at the End of Infusion (Ceoi)
Concentration of Bintrafusp alfa Immediately Before Next Dosing (Ctrough)
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp alfa
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
Maximum Serum Concentration Observed (Cmax) of Bintrafusp alfa
Time at which Cmax Occurs (tmax) of Bintrafusp alfa
Elimination Half-life (t½) of Bintrafusp alfa
Immunogenicity of Bintrafusp alfa, as Assessed by Anti-drug Anti-body (ADA) Assay
Incidence of Dose-Limiting Toxicity (DLT) in Japanese Participants
Number of Japanese Participants With Adverse Events (AE)

Full Information

First Posted
September 7, 2020
Last Updated
January 27, 2023
Sponsor
EMD Serono Research & Development Institute, Inc.
Collaborators
Merck KGaA, Darmstadt, Germany
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1. Study Identification

Unique Protocol Identification Number
NCT04551950
Brief Title
Bintrafusp Alfa Combination Therapy in Participants With Cervical Cancer (INTR@PID 046)
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)
Study Type
Interventional

2. Study Status

Record Verification Date
January 2023
Overall Recruitment Status
Completed
Study Start Date
October 19, 2020 (Actual)
Primary Completion Date
June 15, 2022 (Actual)
Study Completion Date
June 30, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EMD Serono Research & Development Institute, Inc.
Collaborators
Merck KGaA, Darmstadt, Germany

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cervical Cancer
Keywords
Advanced cervical cancer, Bintrafusp alfa, M7824, INTR@PID, Transforming growth factor-beta, Programmed death-ligand 1

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
25 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Cohort 1A:M7824+cisplatin/carboplatin+paclitaxel+bevacizumab
Arm Type
Experimental
Arm Title
Cohort1B:M7824+cisplatin or carboplatin+paclitaxel
Arm Type
Experimental
Arm Title
Cohort 2: M7824+cisplatin+ radiotherapy
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
M7824
Other Intervention Name(s)
Bintrafusp alfa
Intervention Description
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).
Intervention Type
Drug
Intervention Name(s)
Carboplatin
Intervention Description
Carboplatin will be administered intravenously as per standard of care.
Intervention Type
Drug
Intervention Name(s)
Paclitaxel
Intervention Description
Paclitaxel will be administered intravenously as per standard of care.
Intervention Type
Drug
Intervention Name(s)
Bevacizumab
Intervention Description
Bevacizumab will be administrated as indicated for standard of care.
Intervention Type
Drug
Intervention Name(s)
Cisplatin
Intervention Description
Cisplatin will be administered intravenously as per standard of care.
Intervention Type
Radiation
Intervention Name(s)
Radiotherapy
Intervention Description
Participants will receive radiotherapy as per standard of care.
Primary Outcome Measure Information:
Title
Incidence of Dose-Limiting Toxicity (DLT)
Time Frame
Week 1 Day 1 up to Week 4
Title
Number of Participants With Adverse Events (AEs)
Time Frame
Time from first treatment to planned final assessment at approximately 2 years
Secondary Outcome Measure Information:
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
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
Title
Incidence of Dose-Limiting Toxicity (DLT) in Japanese Participants
Time Frame
Week 1 Day 1 up to Week 4
Title
Number of Japanese Participants With Adverse Events (AE)
Time Frame
Time from first treatment to planned final assessment at approximately 2 years

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Medical Responsible
Organizational Affiliation
Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
Official's Role
Study Director
Facility Information:
Facility Name
Stanford Health Care Hospital & Clinics
City
Stanford
State/Province
California
ZIP/Postal Code
94305
Country
United States
Facility Name
Augusta University - formerly Georgia Regents University
City
Augusta
State/Province
Georgia
ZIP/Postal Code
30912
Country
United States
Facility Name
Comprehensive Cancer Centers of Nevada
City
Henderson
State/Province
Nevada
ZIP/Postal Code
89074
Country
United States
Facility Name
University of Cincinnati Physicians Group, LLC - Pharmatech Oncology, Inc
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45206
Country
United States
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
National Cancer Center Hospital
City
Chuo-ku
Country
Japan
Facility Name
Saitama Medical University International Medical Center
City
Hidaka-shi
Country
Japan
Facility Name
Cancer Institute Hospital of JFCR
City
Koto-ku
Country
Japan
Facility Name
Osaka International Cancer Institute
City
Osaka-shi
Country
Japan
Facility Name
Shizuoka Cancer Center
City
Sunto-gun
Country
Japan
Facility Name
Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia
City
Barcelona
Country
Spain
Facility Name
Hospital Universitari Vall d'Hebron - Dept of Oncology
City
Barcelona
Country
Spain
Facility Name
ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia
City
Barcelona
Country
Spain

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing 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
Links:
URL
https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS200647_0046
Description
Trial Awareness and Transparency website
URL
http://medical.emdserono.com/en_US/home.html
Description
US Medical Information website, Medical Resources

Learn more about this trial

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

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