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Completed

NCT Number: NCT04246489

Bintrafusp Alfa Monotherapy in Platinum-Experienced Cervical Cancer

The main purpose of this study was to evaluate clinical efficacy and safety of bintrafusp alfa in participants with advanced, unresectable cervical cancer with disease progression during or after platinum-containing chemotherapy.

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Key information

Conditions

Uterine Cervical Neoplasms Female Urogenital Diseases Female Urogenital Diseases and Pregnancy Complications Genital Diseases Genital Diseases, Female Genital Neoplasms, Female Neoplasms Neoplasms by Site Urogenital Diseases Urogenital Neoplasms Uterine Cervical Diseases Uterine Diseases Uterine Neoplasms

Age range

18 year and older

Sex eligibility

Female

Study type

Interventional

Phase

Phase 2

Primary location

Centro Oncologico Riojano Integral (CORI), La Rioja, Argentina

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Who can participate

Healthy volunteers accepted: No

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

Inclusion criteria

  • Participants who had advanced unresectable and/or metastatic cervical cancer (squamous cell carcinoma, adenocarcinoma, adenosquamous cell carcinoma) with disease progression during or after the prior platinum-containing chemotherapy:
  • The prior platinum-containing chemotherapy may be a systemic treatment for advanced unresectable, recurrent, persistent or metastatic disease or treatment in the adjuvant or neo-adjuvant setting with disease progression or recurrence within 6 months of completion of platinum-containing chemotherapy
  • Participants who previously only received platinum as a radiosensitizer are not eligible
  • Participants must be naïve to checkpoint inhibitors
  • Participants who had measurable disease
  • Participants who provide a tumor tissue sample, either from archival tissue or newly obtained core or excisional biopsy. If the participant received local therapy (For example: radiation therapy or chemoradiotherapy) after the archival tissue was taken, a new biopsy was required
  • Participants who had Eastern Cooperative Oncology Group (ECOG) PS of 0 to 1
  • Life expectancy greater than or equals to (>=) 12 weeks as judged by the Investigator
  • Adequate hematological, hepatic and renal function as defined in the protocol
  • Participants with known Human Immunodeficiency Virus (HIV) infections were in general eligible if the following criteria are met:
  • Clinically indicated participants must be stable on antiretroviral therapy (ART) for at least 4 weeks and agree to adhere to ART
  • had no evidence of documented multi-drug resistance that would prevent effective ART
  • had an HIV viral load of < 400 copies per milliliter (/mL) at Screening
  • had CD4+ T-cell (CD4+) counts >= 350 cells/microliter
  • For participants with a history of an Acquired immunodeficiency syndrome (AIDS)-defining opportunistic infection within the last 12 months, participants may be eligible only after consultation and agreement with the study Medical Monitor
  • If prophylactic antimicrobial drugs were indicated, participants would still be considered eligible upon agreement with the study Medical Monitor
  • Participants with hepatitis B virus (HBV) and/or hepatitis C virus (HCV) infections were in general eligible if the following criteria are met:
  • HBV viral load below the limit of quantification. If medically indicated, participants infected with HBV must be treated and on a stable dose of antivirals at study entry and with planned monitoring and management according to appropriate labeling guidance
  • Participants with a history of HCV infection should have completed curative antiviral treatment and require HCV viral load below the limit of quantification
  • Participants on concurrent HCV treatment should have HCV below the limit of quantification
  • Other protocol defined inclusion criteria could apply

Exclusion criteria

  • Participants with active central nervous system (CNS) metastases causing clinical symptoms or require therapeutic intervention are excluded. Participants with a history of treated CNS metastases (by surgery or radiation therapy) are not eligible unless they have fully recovered from treatment, demonstrated no progression for at least 4 weeks, and are not using steroids for at least 7 days prior to the start of study treatment
  • Participants with interstitial lung disease or has had a history of pneumonitis that has required oral or intravenous (IV) steroids
  • Participants with significant acute or chronic infections
  • Participants with active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
  • Participants with clinically significant cardiovascular/cerebrovascular disease including: cerebral vascular accident/stroke, myocardial infarction, unstable angina, congestive heart failure, or serious cardiac arrhythmia
  • Other protocol defined exclusion criteria could apply

Treatment and study plan

Bintrafusp alfa

Drug

Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, death, unacceptable toxicity and study withdrawal.

Other names: M7824

Primary outcomes

  1. Number of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

    Time frame: Time from first treatment up to 688 days

    Confirmed objective response was defined as the number of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by IRC.

Secondary outcomes

  1. Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

    Time frame: Time from first treatment up to 688 days

    DOR was defined for participants with confirmed response, as the time from first documentation of confirmed objective response (Complete Response [CR] or Partial Response [PR]) according to RECIST 1.1 to the date of first documentation of progression disease (PD) or death due to any cause, whichever occurred first. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. DOR was determined according to RECIST v1.1 and assessed by IRC. Results were calculated based on Kaplan-Meier estimates.

  2. Durable Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)

    Time frame: Time from first treatment up to 688 days

    Durable Response was defined as the number of participants with confirmed objective response (CR or PR) according to RECIST 1.1, determined by IRC with duration of at least 6 months. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

  3. Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs)

    Time frame: Time from first treatment up to 688 days

    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. Serious AE was defined AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial/prolonged inpatient hospitalization; congenital anomaly/birth defect. TEAEs: TEAEs was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious AEs and non-serious AEs. Treatment-related TEAEs: reasonably related to the study intervention. AESIs included Infusion-related reactions, Immune-related AEs, Transforming growth factor- beta (TGF-ß) inhibition mediated skin AE, bleeding and anemia.

  4. Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)

    Time frame: Time from first administration of study drug until the first documentation of PD or death, assessed up to 688 days

    PFS was defined as the time from first administration of study intervention until date of the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Kaplan-Meier estimates was used to calculate PFS.

  5. Number of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by the Investigator

    Time frame: Time from first treatment up to 688 days

    Confirmed objective response was defined as the number of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by Investigator.

  6. Overall Survival (OS)

    Time frame: Time from first administration of study drug up to data cutoff (assessed up to 688 days)

    OS was defined as the time from first administration of study intervention to the date of death due to any cause. The OS was analyzed by using the Kaplan-Meier method.

  7. Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa

    Time frame: At Day 15, Day 29, Day 43, Day 85, Day 127, Day 169, Day 253, Day 337, Day 421, Day 505 and Day 589

    Ctrough was defined as the concentration observed immediately before next dosing (corresponding to pre-dose or trough concentration for multiple dosing).

  8. Serum Concentration at End of Infusion (CEOI) of Bintrafusp Alfa

    Time frame: At Day 1 and Day 29

    Serum Concentration at End of Infusion (CEOI) of bintrafusp alfa is reported.

  9. Number of Participants With Positive Antidrug Antibodies (ADA)

    Time frame: Time from first treatment up to 688 days

    Serum samples were analyzed by a validated assay method to detect the presence of antidrug antibodies (ADA). Number of participants with positive ADA were reported.

  10. Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression

    Time frame: Time from first treatment up to 688 days

    Confirmed objective response was defined as the percentage of participants with a confirmed objective response of complete response (CR) or partial response (PR). CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Confirmed CR = at least 2 determinations of CR at least 4 weeks apart and before progression. Confirmed PR = at least 2 determinations of PR at least 4 weeks apart and before progression (and not qualifying for a CR). Confirmed objective response was determined according to RECIST v1.1 and as adjudicated by IRC through PD-L1 Subgroup. Participants with PD-L1 positive tumors (Combined positive score (CPS) >=1) and PD-L1 negative tumors (CPS<1).

  11. PFS According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) According to Programmed Death Ligand 1 (PD-L1) Expression

    Time frame: Time from first administration of study drug until the first documentation of PD or death, assessed up to 688 days

    PFS was defined as the time from first administration of study intervention until the first documentation of disease progression (PD) or death due to any cause, whichever occurred first. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. PFS was determined according to RECIST v1.1 and as adjudicated by IRC through PD-L1 Subgroup. Participants with PD-L1 positive tumors (Combined positive score (CPS) >=1) and PD-L1 negative tumors (CPS<1).

  12. Overall Survival (OS) as Assessed According to Programmed Death Ligand 1 (PD-L1) Expression

    Time frame: Time from first administration of study drug up to 688 days

    OS was defined as the time from first administration of study intervention to the date of death due to any cause. The OS was analyzed by using the Kaplan-Meier method. Participants with PD-L1 positive tumors (Combined positive score (CPS) >=1) and PD-L1 negative tumors (CPS<1).

Sponsors and collaborators

Lead sponsor

EMD Serono Research & Development Institute, Inc.

Industry

Collaborators

  • Merck KGaA, Darmstadt, Germany

Registry information

Official study title

A Phase II, Multicenter, Open Label Study of Bintrafusp Alfa (M7824) Monotherapy in Participants With Advanced, Unresectable Cervical Cancer With Disease Progression During or After Platinum-Containing Chemotherapy

Important dates

Study start
2020
Primary completion
2022
Study completion
2022
First posted
Jan 29, 2020
Registry last updated
Oct 23, 2023

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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