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

Sponsor

EMD Serono Research & Development Institute, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04551950

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

Enrollment

Locations

Arms

43.1

Anticipated Duration (Months)

1.9

Patients Per Site

Patients Per Site Per Month

Study Details

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.

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

Study Design

Study Type:

Interventional

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 :

Oct 19, 2020

Actual Primary Completion Date :

Jun 15, 2022

Anticipated Study Completion Date :

May 24, 2024

Arms and Interventions

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 Names: 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 Names: 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 Names: 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.

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 Names:

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 Names:

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 Names:

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

Primary Outcome Measures

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

Secondary Outcome Measures

Concentration of Bintrafusp alfa Immediately at the End of Infusion (Ceoi) [Before the first infusion up to 28 days after the last treatment, assessed up to 2 years]
Concentration of Bintrafusp alfa Immediately Before Next Dosing (Ctrough) [Before the first infusion up to 28 days after the last treatment, assessed up to 2 years]
Area Under the Concentration-Time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp alfa [Before the first infusion up to 28 days after the last treatment, assessed up to 2 years]
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 [Before the first infusion up to 28 days after the last treatment, assessed up to 2 years]
Maximum Serum Concentration Observed (Cmax) of Bintrafusp alfa [Before the first infusion up to 28 days after the last treatment, assessed up to 2 years]
Time at which Cmax Occurs (tmax) of Bintrafusp alfa [Before the first infusion up to 28 days after the last treatment, assessed up to 2 years]
Elimination Half-life (t½) of Bintrafusp alfa [Before the first infusion up to 28 days after the last treatment, assessed up to 2 years]
Immunogenicity of Bintrafusp alfa, as Assessed by Anti-drug Anti-body (ADA) Assay [Prior to the first infusion up to 28 days after the last treatment,assessed up to 2 years]
Incidence of Dose-Limiting Toxicity (DLT) in Japanese Participants [Week 1 Day 1 up to Week 4]
Number of Japanese Participants With Adverse Events (AE) [Time from first treatment to planned final assessment at approximately 2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Stanford Health Care Hospital & Clinics	Stanford	California	United States	94305
2	Augusta University - formerly Georgia Regents University	Augusta	Georgia	United States	30912
3	Comprehensive Cancer Centers of Nevada	Henderson	Nevada	United States	89074
4	University of Cincinnati Physicians Group, LLC - Pharmatech Oncology, Inc	Cincinnati	Ohio	United States	45206
5	UT Southwestern Medical Center	Dallas	Texas	United States	75390
6	National Cancer Center Hospital	Chuo-ku		Japan
7	Saitama Medical University International Medical Center	Hidaka-shi		Japan
8	Cancer Institute Hospital of JFCR	Koto-ku		Japan
9	Osaka International Cancer Institute	Osaka-shi		Japan
10	Shizuoka Cancer Center	Sunto-gun		Japan
11	Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia	Barcelona		Spain
12	Hospital Universitari Vall d'Hebron - Dept of Oncology	Barcelona		Spain
13	ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia	Barcelona		Spain