Uterine Cervical Neoplasms
Conditions
Keywords
M7824, INTR@PID, Bintrafusp alfa, programmed death-ligand 1, Cervical Cancer, Transforming growth factor-β (TGF-β)
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.
Interventions
DRUGBintrafusp alfa
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.
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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). |
| 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). |
| 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). |
| 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). |
Countries
Argentina, Australia, Belgium, Brazil, China, France, Hungary, Japan, Russia, South Korea, Spain, United States
Participant flow
Pre-assignment details
A total of 203 participants were screened, of which 146 participants received bintrafusp alfa monotherapy.
Participants by arm
| Arm | Count |
|---|---|
| Bintrafusp Alfa Participants received an intravenous infusion of 1200 milligrams (mg) bintrafusp alfa once every 2 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. | 146 |
| Total | 146 |
Baseline characteristics
| Characteristic | Bintrafusp Alfa |
|---|---|
| Age, Continuous | 52 Years STANDARD_DEVIATION 12.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 11 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 132 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 3 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 90 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 17 Participants |
| Race (NIH/OMB) White | 37 Participants |
| Sex: Female, Male Female | 146 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 76 / 146 |
| other Total, other adverse events | 139 / 146 |
| serious Total, serious adverse events | 94 / 146 |
Outcome results
Primary
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)
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.
Time frame: Time from first treatment up to 688 days
Population: FAS included all participants who were administered at least one dose of bintrafusp alfa.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bintrafusp Alfa | 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) | 32 Participants |
Secondary
Durable Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC)
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.
Time frame: Time from first treatment up to 688 days
Population: FAS included all participants who were administered at least one dose of bintrafusp alfa.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bintrafusp Alfa | Durable Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Independent Review Committee (IRC) | 19 Participants |
Secondary
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)
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.
Time frame: Time from first treatment up to 688 days
Population: FAS included all participants who were administered at least one dose of bintrafusp alfa.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bintrafusp Alfa | 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) | NA months |
Secondary
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
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.
Time frame: Time from first treatment up to 688 days
Population: FAS included all participants who were administered at least one dose of bintrafusp alfa.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bintrafusp Alfa | 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 | 25 Participants |
Secondary
Number of Participants With Positive Antidrug Antibodies (ADA)
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.
Time frame: Time from first treatment up to 688 days
Population: Immunogenicity analysis set included all participants who received at least one dose of bintrafusp alfa and who had at least one valid result of ADA.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Bintrafusp Alfa | Number of Participants With Positive Antidrug Antibodies (ADA) | 33 Participants |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs)
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.
Time frame: Time from first treatment up to 688 days
Population: Safety analysis set included all participants who were administered at least one dose of bintrafusp alfa
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Bintrafusp Alfa | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) | TEAE's | 145 Participants |
| Bintrafusp Alfa | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) | Treatment Related TEAEs | 106 Participants |
| Bintrafusp Alfa | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) | AESI: Infusion-related reaction | 5 Participants |
| Bintrafusp Alfa | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) | AESI: Immune-related AE | 49 Participants |
| Bintrafusp Alfa | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) | AESI: TGF-beta inhibition mediated skin AE | 7 Participants |
| Bintrafusp Alfa | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) | AESI: Anemia | 82 Participants |
| Bintrafusp Alfa | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Treatment-Related TEAEs, Including Adverse Event of Special Interests (AESIs) | AESI: Bleeding events | 81 Participants |
Secondary
Overall Survival (OS)
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.
Time frame: Time from first administration of study drug up to data cutoff (assessed up to 688 days)
Population: FAS included all participants who were administered at least one dose of bintrafusp alfa.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bintrafusp Alfa | Overall Survival (OS) | 13.7 months |
Secondary
Overall Survival (OS) as Assessed According to Programmed Death Ligand 1 (PD-L1) Expression
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).
Time frame: Time from first administration of study drug up to 688 days
Population: FAS included all participants who were administered at least one dose of bintrafusp alfa. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified categories for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Bintrafusp Alfa | Overall Survival (OS) as Assessed According to Programmed Death Ligand 1 (PD-L1) Expression | PD-L1 positive tumors (CPS>=1) | 17.5 months |
| Bintrafusp Alfa | Overall Survival (OS) as Assessed According to Programmed Death Ligand 1 (PD-L1) Expression | PD-L1 negative tumors (CPS<1) | 8.7 months |
Secondary
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
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).
Time frame: Time from first treatment up to 688 days
Population: FAS included all participants who were administered at least one dose of bintrafusp alfa. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified categories for this outcome measure.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Bintrafusp Alfa | 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 | PD-L1 positive tumors (CPS>=1) | 25.6 percentage of participants |
| Bintrafusp Alfa | 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 | PD-L1 negative tumors (CPS <1) | 18.2 percentage of participants |
Secondary
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
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).
Time frame: Time from first administration of study drug until the first documentation of PD or death, assessed up to 688 days
Population: FAS included all participants who were administered at least one dose of bintrafusp alfa. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified categories for this outcome measure.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Bintrafusp Alfa | 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 | PD-L1 positive tumors (CPS>=1) | 1.9 months |
| Bintrafusp Alfa | 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 | PD-L1 negative tumors (CPS<1) | 1.9 months |
Secondary
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC)
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.
Time frame: Time from first administration of study drug until the first documentation of PD or death, assessed up to 688 days
Population: FAS included all participants who were administered at least one dose of bintrafusp alfa.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Bintrafusp Alfa | Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Independent Review Committee (IRC) | 1.9 months |
Secondary
Serum Concentration at End of Infusion (CEOI) of Bintrafusp Alfa
Serum Concentration at End of Infusion (CEOI) of bintrafusp alfa is reported.
Time frame: At Day 1 and Day 29
Population: PK analysis set included all participants who completed at least one dose of Bintrafusp Alfa and who provided at least one sample with a measurable concentration of Bintrafusp Alfa. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified time points for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Bintrafusp Alfa | Serum Concentration at End of Infusion (CEOI) of Bintrafusp Alfa | Day 1 | 469 mcg/mL | Geometric Coefficient of Variation 21.9 |
| Bintrafusp Alfa | Serum Concentration at End of Infusion (CEOI) of Bintrafusp Alfa | Day 29 | 546 mcg/mL | Geometric Coefficient of Variation 24.1 |
Secondary
Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa
Ctrough was defined as the concentration observed immediately before next dosing (corresponding to pre-dose or trough concentration for multiple dosing).
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
Population: Pharmacokinetic (PK) analysis set included all participants who completed at least one dose of bintrafusp alfa and who provided at least one sample with a measurable concentration of bintrafusp alfa. Here, Overall Number of Participants Analyzed signifies those participants who were evaluable for this outcome measure and number analyzed signifies those participants who were evaluable at specified time points for this outcome measure.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| Bintrafusp Alfa | Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa | Day 15 | 73.7 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 55.3 |
| Bintrafusp Alfa | Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa | Day 29 | 107 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 48.7 |
| Bintrafusp Alfa | Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa | Day 43 | 108 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 53 |
| Bintrafusp Alfa | Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa | Day 85 | 115 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 44.9 |
| Bintrafusp Alfa | Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa | Day 127 | 107 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 69 |
| Bintrafusp Alfa | Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa | Day 169 | 137 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 41 |
| Bintrafusp Alfa | Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa | Day 253 | 101 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 45.8 |
| Bintrafusp Alfa | Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa | Day 337 | 120 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 50.9 |
| Bintrafusp Alfa | Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa | Day 421 | 103 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 56.4 |
| Bintrafusp Alfa | Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa | Day 505 | 220 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 22.4 |
| Bintrafusp Alfa | Serum Pre-Dose Concentrations (Ctrough) of Bintrafusp Alfa | Day 589 | 154 microgram per milliliter (mcg/mL) | Geometric Coefficient of Variation 10.4 |