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

Merck KGaA (EMD Serono)

Status and phase: Completed; Phase 1

Conditions: Cervical Cancer

Treatments: Drug: Bevacizumab; Drug: M7824; Drug: Carboplatin; Radiation: Radiotherapy; Drug: Cisplatin; Drug: Paclitaxel

Study type: Interventional

Funder types: Industry

Identifiers

NCT04551950

2020-001561-36 (EudraCT Number)

MS200647_0046

Details and patient eligibility

About

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.

Enrollment: 25 patients

Sex: Female

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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25 participants in 3 patient groups

Cohort 1A:M7824+Cisplatin/Carboplatin+Paclitaxel+Bevacizumab

Experimental group

Treatment:

Drug: Cisplatin

Drug: Paclitaxel

Drug: Carboplatin

Drug: M7824

Drug: Bevacizumab

Cohort1B:M7824+Cisplatin or Carboplatin+Paclitaxel

Experimental group

Treatment:

Drug: Cisplatin

Drug: Paclitaxel

Drug: Carboplatin

Drug: M7824

Cohort 2: M7824+Cisplatin+ Radiotherapy

Experimental group

Treatment:

Drug: Cisplatin

Drug: M7824

Radiation: Radiotherapy