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Completed

NCT Number: NCT04551950

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

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.

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Key information

Conditions

Cervical Cancer Bone Diseases Bone Diseases, Developmental Camurati-Engelmann Syndrome Congenital, Hereditary, and Neonatal Diseases and Abnormalities Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genetic Diseases, Inborn Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Musculoskeletal Diseases Neoplasms Neoplasms by Site Osteochondrodysplasias Urogenital Diseases Urogenital Neoplasms Uterine Cervical Diseases Uterine Cervical Neoplasms Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 1

Primary location

National Cancer Center Hospital, Chūōku, Japan

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

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).

Other names: Bintrafusp alfa

carboplatin

Drug

Carboplatin was administered intravenously as per standard of care.

paclitaxel

Drug

Paclitaxel was administered intravenously as per standard of care.

Bevacizumab

Drug

Bevacizumab was administrated as indicated for standard of care.

Cisplatin

Drug

Cisplatin was administered intravenously as per standard of care.

Radiotherapy

Radiation

Participants received radiotherapy as per standard of care.

Primary outcomes

  1. Number of Participants With Dose-Limiting Toxicities (DLTs)

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

    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.

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

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

    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.

Secondary outcomes

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

    Time frame: Pre-dose Up to 20 months

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

  2. Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa

    Time frame: Pre-dose Up to 20 months

    Ctrough was the serum concentration observed immediately before next dosing.

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

    Time frame: Pre-dose Up to 20 months

    The area under the concentration-time curve (AUC) from time zero (= dosing time) to the last sampling time (tlast) at which the concentration is at or above the lower limit of quantification. Calculated using the mixed log-linear trapezoidal rule (linear up, log down).

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

    Time frame: Pre-dose Up to 20 months

    AUC0-inf was calculated by combining AUC0-t and AUCextra. AUCextra represents an extrapolated value obtained by Clast pred/Lambda z, where Clast pred was the calculated serum concentration at the last sampling time point at which the measured serum concentration is at or above the Lower Limit of quantification (LLQ) and Lambda z was the apparent terminal rate constant determined by log-linear regression analysis of the measured serum concentrations of the terminal log-linear phase.

  5. Maximum Observed Serum Concentration (Cmax) of Bintrafusp Alfa

    Time frame: Pre-dose Up to 20 months

    Cmax was obtained directly from the concentration versus time curve.

  6. Time to Reach Maximum Serum Concentration (Tmax) of Bintrafusp Alfa

    Time frame: Pre-dose Up to 20 months

    The time to reach the maximum observed concentration collected during a dosing interval. Tmax was obtained directly from the concentration versus time curve.

  7. Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa

    Time frame: Pre-dose Up to 20 months

    Elimination Half Life (T1/2) was defined as the time required for the concentration or amount of drug in the body to be reduced by one-half. Elimination half-life determined as 0.693/ Lamda z(λz), λz=terminal first order (elimination) rate constant.

  8. Number of Participants With Positive Anti-Drug Antibody (ADA) of Bintrafusp Alfa

    Time frame: Pre-dose Up to 20 months

    A validated method was applied to detect ADAs in the presence of drug in human serum. The ADA titers of positive samples were determined.

  9. Number of Japanese Participants With Dose-Limiting Toxicities (DLTs)

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

    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.

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

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

    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.

Sponsors and collaborators

Lead sponsor

EMD Serono Research & Development Institute, Inc.

Industry

Collaborators

  • Merck KGaA, Darmstadt, Germany

Registry information

Official study 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)

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Sep 16, 2020
Registry last updated
Mar 8, 2024

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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