Clinical Trials /

Bintrafusp Alfa Combination Therapy in Participants With Cervical Cancer

NCT04551950

Description:

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.

Related Conditions:
  • Cervical Adenocarcinoma
  • Cervical Adenosquamous Carcinoma
  • Cervical Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: Bintrafusp Alfa Combination Therapy in Participants With Cervical Cancer
  • Official Title: Safety Study of Bintrafusp Alfa in Combination With Other Anti-cancer Therapies in Participants With Locally Advanced or Advanced Cervical Cancer

Clinical Trial IDs

  • ORG STUDY ID: MS200647_0046
  • SECONDARY ID: 2020-001561-36
  • NCT ID: NCT04551950

Conditions

  • Cervical Cancer

Interventions

DrugSynonymsArms
M7824Bintrafusp alfaCohort 1A:M7824+cisplatin/carboplatin+paclitaxel+bevacizumab
CarboplatinCohort 1A:M7824+cisplatin/carboplatin+paclitaxel+bevacizumab
PaclitaxelCohort 1A:M7824+cisplatin/carboplatin+paclitaxel+bevacizumab
BevacizumabCohort 1A:M7824+cisplatin/carboplatin+paclitaxel+bevacizumab
CisplatinCohort 1A:M7824+cisplatin/carboplatin+paclitaxel+bevacizumab

Purpose

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.

Trial Arms

NameTypeDescriptionInterventions
Cohort 1A:M7824+cisplatin/carboplatin+paclitaxel+bevacizumabExperimental
  • M7824
  • Carboplatin
  • Paclitaxel
  • Bevacizumab
  • Cisplatin
Cohort1B:M7824+cisplatin or carboplatin+paclitaxelExperimental
  • M7824
  • Carboplatin
  • Paclitaxel
  • Cisplatin
Cohort 2: M7824+cisplatin+ radiotherapyExperimental
  • M7824
  • Cisplatin

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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:Female
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of Dose-Limiting Toxicity (DLT)
Time Frame:Week 1 Day 1 up to Week 4
Safety Issue:
Description:

Secondary Outcome Measures

Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Incidence of Dose-Limiting Toxicity (DLT) in Japanese Participants
Time Frame:Week 1 Day 1 up to Week 4
Safety Issue:
Description:
Measure:Number of Japanese Participants With Adverse Events (AE)
Time Frame:Time from first treatment to planned final assessment at approximately 2 years
Safety Issue:
Description:

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:EMD Serono Research & Development Institute, Inc.

Trial Keywords

  • Advanced cervical cancer
  • Bintrafusp alfa
  • M7824
  • INTR@PID
  • Transforming growth factor-beta
  • Programmed death-ligand 1

Last Updated

September 10, 2020