Clinical trial NCT04551950: 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
Overall status: COMPLETED
Phase: PHASE1
Conditions: Cervical Cancer
Keywords: Advanced cervical cancer
Bintrafusp alfa
M7824
INTR@PID
Transforming growth factor-beta
Programmed death-ligand 1
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2020-09-16
Enrollment: 25
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Up to 4 weeks after first administration of study intervention
measure: Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Time from first treatment assessed up to approximately 20 months
Secondary outcomes:
measure: Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa
timeFrame: Pre-dose Up to 20 months
measure: Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa
timeFrame: Pre-dose Up to 20 months
measure: Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa
timeFrame: Pre-dose Up to 20 months
measure: Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa
timeFrame: Pre-dose Up to 20 months
measure: Maximum Observed Serum Concentration (Cmax) of Bintrafusp Alfa
timeFrame: Pre-dose Up to 20 months
measure: Time to Reach Maximum Serum Concentration (Tmax) of Bintrafusp Alfa
timeFrame: Pre-dose Up to 20 months
measure: Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa
timeFrame: Pre-dose Up to 20 months
measure: Number of Participants With Positive Anti-Drug Antibody (ADA) of Bintrafusp Alfa
timeFrame: Pre-dose Up to 20 months
measure: Number of Japanese Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Up to 4 weeks after first administration of study intervention
measure: Number of Japanese Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
timeFrame: Time from first treatment assessed up to approximately 20 months
Other outcomes:
Locations:
city: Stanford
country: United States
facility: Stanford Health Care Hospital & Clinics
state: California
city: Augusta
country: United States
facility: Augusta University - formerly Georgia Regents University
state: Georgia
city: Henderson
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Cincinnati
country: United States
facility: University of Cincinnati Physicians Group, LLC - Pharmatech Oncology, Inc
state: Ohio
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Chuo-ku
country: Japan
facility: National Cancer Center Hospital
city: Hidaka-shi
country: Japan
facility: Saitama Medical University International Medical Center
city: Koto-ku
country: Japan
facility: Cancer Institute Hospital of JFCR
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron - Dept of Oncology
city: Barcelona
country: Spain
facility: ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: