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

Phase 1CompletedNCT04551950

EMD Serono Research & Development Institute, Inc.25 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Cervical Cancer

Interventions

M7824DRUG

Participants received bintrafusp alfa until confirmed disease progression, death, unacceptable toxicity and study withdrawal maximum of 2 years (at the discretion of the Investigator).

CarboplatinDRUG

Carboplatin was administered intravenously as per standard of care.

PaclitaxelDRUG

Paclitaxel was administered intravenously as per standard of care.

Eligibility

Sex: FEMALEMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (13)

Stanford Health Care Hospital & Clinics

Stanford, California, United States

Augusta University - formerly Georgia Regents University

Augusta, Georgia, United States

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, United States

Outcomes

Primary Outcomes

Number of Participants With Dose-Limiting Toxicities (DLTs)

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.

Time frame: Up to 4 weeks after first administration of study intervention

Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)

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 frame: Time from first treatment assessed up to approximately 20 months

Secondary Outcomes

Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa

Ceoi was the observed concentration at the end of the infusion period. This was taken directly from the observed Bintrafusp Alfa concentration-time data.

Data from ClinicalTrials.gov

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