Bintrafusp Alfa Monotherapy in Platinum-Experienced Cervical Cancer

Phase 2

Completed

Conditions: Uterine Cervical Neoplasms

Interventions: Drug: Bintrafusp alfa

Registration Number: NCT04246489

Lead Sponsor: EMD Serono Research & Development Institute, Inc.

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Female

Target Recruitment: 146

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:
1. 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
2. Participants who previously only received platinum as a radiosensitizer are not eligible
3. 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:
1. Clinically indicated participants must be stable on antiretroviral therapy (ART) for at least 4 weeks and agree to adhere to ART
2. had no evidence of documented multi-drug resistance that would prevent effective ART
3. had an HIV viral load of < 400 copies per milliliter (/mL) at Screening
4. had CD4+ T-cell (CD4+) counts >= 350 cells/microliter
5. 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
6. 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:
1. 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
2. Participants with a history of HCV infection should have completed curative antiviral treatment and require HCV viral load below the limit of quantification
3. 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

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Bintrafusp alfa	Bintrafusp alfa	-

Primary Outcome Measures

Name	Time	Method
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 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 Outcome Measures

Name	Time	Method
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)	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.
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 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.
Overall Survival (OS)	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.
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa	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).
Serum Concentration at End of Infusion (CEOI) of Bintrafusp Alfa	At Day 1 and Day 29	Serum Concentration at End of Infusion (CEOI) of bintrafusp alfa is reported.
Number of Participants With Positive Antidrug Antibodies (ADA)	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.
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 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).
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 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.
Durable Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)	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.
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs)	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.
Overall Survival (OS) as Assessed According to Programmed Death Ligand 1 (PD-L1) Expression	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).
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 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).

Trial Locations

Locations (73): Highlands Oncology Group
🇺🇸
Fayetteville, Arkansas, United States
University of Arkansas Medical Sciences
🇺🇸
Little Rock, Arkansas, United States
Stanford University Hospital and Clinics - Stanford Cancer Center
🇺🇸
Stanford, California, United States
The Stamford Hospital
🇺🇸
Stamford, Connecticut, United States
Karmanos Cancer Institute
🇺🇸
Farmington Hills, Michigan, United States
Washington University in St. Louis
🇺🇸
Saint Louis, Missouri, United States
Comprehensive Cancer Centers of Nevada
🇺🇸
Henderson, Nevada, United States
UC Health Clinical Trials Office
🇺🇸
Cincinnati, Ohio, United States
Oregon Health & Science University
🇺🇸
Portland, Oregon, United States
The West Clinic
🇺🇸
Germantown, Tennessee, United States
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Highlands Oncology Group
🇺🇸Fayetteville, Arkansas, United States