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

NCT04551950 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: MS200647_00462020-001561-36
• Study Type: interventional
• Target: 25
• Locations: 3 countries
• Sites: 13

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.

Conditions

Cervical Cancer

Keywords

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

Outcome Measures

Primary Outcomes (2)

• 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.

  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 from first treatment assessed up to approximately 20 months

Secondary Outcomes (10)

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

  Pre-dose Up to 20 months

• Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa

  Pre-dose Up to 20 months

• Area Under the Serum Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa

  Pre-dose Up to 20 months

• Area Under the Serum Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa

  Pre-dose Up to 20 months

• Maximum Observed Serum Concentration (Cmax) of Bintrafusp Alfa

  Pre-dose Up to 20 months

Study Arms (3)

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

EXPERIMENTAL

Drug: M7824; Drug: Carboplatin; Drug: Paclitaxel; Drug: Bevacizumab; Drug: Cisplatin

Cohort1B:M7824+Cisplatin or Carboplatin+Paclitaxel

EXPERIMENTAL

Drug: M7824; Drug: Carboplatin; Drug: Paclitaxel; Drug: Cisplatin

Cohort 2: M7824+Cisplatin+ Radiotherapy

EXPERIMENTAL

Drug: M7824; Drug: Cisplatin; Radiation: Radiotherapy

Interventions

M7824 DRUG

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

Also known as: Bintrafusp alfa

Cohort 1A:M7824+Cisplatin/Carboplatin+Paclitaxel+Bevacizumab; Cohort 2: M7824+Cisplatin+ Radiotherapy; Cohort1B:M7824+Cisplatin or Carboplatin+Paclitaxel

Carboplatin DRUG

Carboplatin was administered intravenously as per standard of care.

Cohort 1A:M7824+Cisplatin/Carboplatin+Paclitaxel+Bevacizumab; Cohort1B:M7824+Cisplatin or Carboplatin+Paclitaxel

Paclitaxel DRUG

Paclitaxel was administered intravenously as per standard of care.

Cohort 1A:M7824+Cisplatin/Carboplatin+Paclitaxel+Bevacizumab; Cohort1B:M7824+Cisplatin or Carboplatin+Paclitaxel

Bevacizumab DRUG

Bevacizumab was administrated as indicated for standard of care.

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

Cisplatin DRUG

Cisplatin was administered intravenously as per standard of care.

Cohort 1A:M7824+Cisplatin/Carboplatin+Paclitaxel+Bevacizumab; Cohort 2: M7824+Cisplatin+ Radiotherapy; Cohort1B:M7824+Cisplatin or Carboplatin+Paclitaxel

Radiotherapy RADIATION

Participants received radiotherapy as per standard of care.

Cohort 2: M7824+Cisplatin+ Radiotherapy

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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
• 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

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (13)

Stanford Health Care Hospital & Clinics

Stanford, California, 94305, United States

Location

Augusta University - formerly Georgia Regents University

Augusta, Georgia, 30912, United States

Location

Comprehensive Cancer Centers of Nevada

Henderson, Nevada, 89074, United States

Location

University of Cincinnati Physicians Group, LLC - Pharmatech Oncology, Inc

Cincinnati, Ohio, 45206, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

National Cancer Center Hospital

Chūōku, Japan

Location

Saitama Medical University International Medical Center

Hidaka-shi, Japan

Location

Cancer Institute Hospital of JFCR

Kōtoku, Japan

Location

Osaka International Cancer Institute

Osaka, Japan

Location

Shizuoka Cancer Center

Sunto-gun, Japan

Location

Hospital Clinic i Provincial de Barcelona - Servicio de Oncologia

Barcelona, Spain

Location

Hospital Universitari Vall d'Hebron - Dept of Oncology

Barcelona, Spain

Location

ICO l´Hospitalet - Hospital Duran i Reynals - Servicio de Oncologia

Barcelona, Spain

Location

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Camurati-Engelmann Syndrome

Interventions

bintrafusp alfa protein, human; Carboplatin; Paclitaxel; Bevacizumab; Cisplatin; Radiotherapy

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Osteochondrodysplasias; Bone Diseases, Developmental; Bone Diseases; Musculoskeletal Diseases; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Therapeutics

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 7, 2020
• First Posted: September 16, 2020
• Study Start: October 19, 2020
• Primary Completion: June 15, 2022
• Study Completion: June 30, 2022
• Last Updated: March 8, 2024
• Results First Posted: March 8, 2024

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will not share

Locations

JP (5); ES (3); US (5)