Carcinoma, Non-Small-Cell Lung
Conditions
Keywords
Non-small Cell Lung Cancer, Bintrafusp alfa (proposed INN), M7824, Stage IV, INTR@PID LUNG 024
Brief summary
The main purpose of the study was to evaluate the safety and tolerability of M7824 in combination with chemotherapy.
Interventions
DRUGCisplatin
Cisplatin was administered intravenously at a dose of 75 milligrams per meter square (mg/m\^2) over 60 minutes every 21 days for 4 cycles (each cycle is 21 days).
DRUGCarboplatin
Carboplatin was administered at area under the concentration-time Curve (AUC) 5 when combined with pemetrexed over 30 to 60 minutes every 21 days for 4 cycles (each cycle is 21 days).
DRUGPemetrexed
Pemetrexed was administered intravenously at a dose of 500 mg/ m\^2 over 10 minutes every 21 days.
DRUGNab-paclitaxel
Nab-paclitaxel was administered intravenously at as dose of 100 mg/m\^2 over 30 minutes in a 21 days cycle on Day 1, 8, and 15 in each cycle for 4 cycles (each cycle is 21 days).
DRUGGemcitabine
Gemcitabine was administered intravenously at a dose of 1250 mg/m\^2 over 30 minutes in a 21 days cycle on Day 1, and 8, in each cycle for 4 cycles (each cycle is 21 days).
DRUGDocetaxel
Docetaxel was administered intravenously at a dose of 75 mg/m\^2 over 60 minutes every 21 days for 4 cycles (each cycle is 21 days).
DRUGM7824
M7824 was administered intravenously at a dose of 2400 mg every 21 days in combination with chemotherapy for 4 cycles (each cycle is 21 days) followed by up to 31 cycles in maintenance with M7824 and pemetrexed.
DRUGBintrafusp alfa
M7824 was administered intravenously at a dose of 2400 mg every 21 days in combination with chemotherapy for 4 cycles (each cycle is 21 days) followed by up to 31 cycles in maintenance with M7824 alone.
DRUGPaclitaxel
Paclitaxel was administered intravenously at a dose of 200 mg/m2 over 3 hours every 3 weeks for 4 cycles (each cycle is 21 days).
Sponsors
Merck KGaA, Darmstadt, Germany
EMD Serono Research & Development Institute, Inc.
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Participants greater than or equals to (\>=) 18 years of age inclusive at the time of signing the informed consent * Participants who have histologically confirmed diagnosis of Stage IV NSCLC: 1. Participants in Cohort A, B, and C must not have received prior systemic therapy treatment for their Stage IV NSCLC 2. Participants who had disease progression on previous treatment with Programmed death-ligand 1 (PD- L1) inhibitors in combination with platinum-based chemotherapy are enrolled in Cohort D, as long as therapy was completed at least 28 days of the first study intervention. * Have measurable disease based on Response evaluation criteria in solid tumors (RECIST) 1.1 * Have a life expectancy of at least 3 months * Availability of archived tumor material (less than \[\<\] 6 months old) adequate for biomarker analysis is mandatory at Screening, central laboratory confirmation is required. Fresh biopsies should be collected if archived tumor material is not available * Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at study entry and date of first dose
Exclusion criteria
* The participant's tumor harbors an epidermal growth factor receptor (EGFR) sensitizing (activating) mutation,ROS1 rearrangement, or BRAF V600E mutation or anaplastic lymphoma kinase (ALK) positive, if targeted therapy is locally approved * Mixed small cell with NSCLC cancer histology * Has received major surgery within 4 weeks prior to the first dose of study intervention; received thoracic radiation therapy (RT) of \> 30 gray (Gy) within 6 months prior to the first dose of study intervention * Previous malignant disease (other than the target malignancy to be investigated in this study) within the last 3 years * Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are clinically stable for at least 2 weeks after the end of the RT and, have no evidence of new or enlarging brain metastases evaluated by imaging, preferably brain magnetic resonance imaging (MRI) * Known severe hypersensitivity to study intervention or any components in their formulations * For participants in Cohort A, B and C: Has received prior systemic therapy for Stage IV NSCLC, including anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-Cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) antibody (including ipilimumab or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways) * Unable to tolerate computed tomography (CT) or MRI in the opinion of the Investigator and/or allergy to contrast material.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-Limiting Toxicities (DLTs) | Day 1 Week 1 up to Week 3 | 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/Cubic Millimeter(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. |
| Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Time from first treatment assessed up to approximately 26 months | An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether considered related to the medicinal product or protocol-specified procedure. 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. TEAE was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious TEAEs and non-serious TEAEs. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator | Time from first administration of study drug until the first documentation of PD or death, assessed up to approximately 26 months | 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. |
| Overall Survival (OS) | Time from first treatment assessed up to approximately 26 months | 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) | Time from first documentation of a confirmed objective response to PD or death due to any cause (assessed up to approximately 26 months) | 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. Results were calculated based on Kaplan-Meier estimates. |
| Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa | Predose, Day 22, Day 43, Day 64 and Day 85 | Ctrough was the serum concentration observed immediately before next dosing. |
| Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa | Predose, Day 22, Day 43, Day 64 and Day 85 | 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). |
| Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator (IRC) | Time from first treatment assessed up to approximately 26 months | Percentage of participants with confirmed objective response that is at least one overall assessment of complete response (CR) or partial response (PR) reported here. 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. |
| Maximum Observed Plasma Concentration (Cmax) of Bintrafusp Alfa | Predose, Day 22, Day 43, Day 64 and Day 85 | Cmax was obtained directly from the concentration versus time curve. |
| Time to Reach Maximum Plasma Concentration (Tmax) of Bintrafusp Alfa | Predose, Day 22, Day 43, Day 64 and Day 85 | The time to reach the maximum observed concentration collected during a dosing interval. Tmax was obtained directly from the concentration versus time curve. |
| Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa | Predose, Day 22, Day 43, Day 64 and Day 85 | Elimination half-life determined as 0.693/terminal first order (elimination) rate constant. |
| Number of Participants With Positive Antidrug Antibodies (ADA) | Time from first treatment assessed up to approximately 26 months | 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. |
| Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa | Predose, Day 22, Day 43, Day 64 and Day 85 | The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from terminal first order (elimination) rate constant determination. AUC0-inf= AUC0-tlast +Clast pred/ terminal first order (elimination) rate constant. |
| Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa | Predose, Day 22, Day 43, Day 64 and Day 85 | Ceoi was the observed concentration at the end of the infusion period. This was taken directly from the observed Bintrafusp Alfa concentration-time data. |
Countries
Belgium, France, United States
Participant flow
Pre-assignment details
A total of 127 participants were screened out of which 70 participants who received study intervention.
Participants by arm
| Arm | Count |
|---|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed Participants received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin 75 mg/ m\^2 (per meter square) over 60 minutes or Carboplatin at area under the concentration-time Curve (AUC) 5 when combined with pemetrexed at a dose of 500 mg/ m\^2 over 30 to 60 minutes every 21 days for 4 cycles (each cycle is 21 days) until confirmed disease progression, unacceptable toxicity, study withdrawal or death. | 40 |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel Participants received 2400 mg Bintrafusp alfa along with Carboplatin at area under the concentration-time Curve (AUC) 6 when combined with nab-paclitaxel at as dose of 100 mg/m\^2 over 30 to 60 minutes(Nab- paclitaxel was administered on Day 1, 8, and 15), and Paclitaxel at a dose of 200 mg/m2 over 3 hours every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death. | 9 |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine Participants received 2400 mg Bintrafusp alfa along with Cisplatin at a dose of 75 milligrams per meter square (mg/m\^2) over 60 minutes or Carboplatin at area under the concentration-time Curve (AUC) 5 when combined with gemcitabine at a dose of 1250 mg/m\^2 over 30 to 60 minutes every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death. | 9 |
| Cohort D: Bintrafusp Alfa + Docetaxel Participants received 2400 mg Bintrafusp alfa along with Docetaxel at a dose of 75 mg/m\^2 over 60 minutes every 21 days for 4 cycles until confirmed disease progression, unacceptable toxicity, study withdrawal or death. | 12 |
| Total | 70 |
Baseline characteristics
| Characteristic | Total | Cohort D: Bintrafusp Alfa + Docetaxel | Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed |
|---|---|---|---|---|---|
| Age, Continuous | 62 Years STANDARD_DEVIATION 9.7 | 60 Years STANDARD_DEVIATION 7.7 | 61 Years STANDARD_DEVIATION 11.2 | 64 Years STANDARD_DEVIATION 8.7 | 63 Years STANDARD_DEVIATION 10.3 |
| Race/Ethnicity, Customized Ethnicity-Not Hispanic or Latino | 29 Participants | 3 Participants | 3 Participants | 8 Participants | 15 Participants |
| Race/Ethnicity, Customized Ethnicity-Unknown or Not Reported | 41 Participants | 9 Participants | 6 Participants | 1 Participants | 25 Participants |
| Race/Ethnicity, Customized Race-Black or African American | 3 Participants | 0 Participants | 0 Participants | 2 Participants | 1 Participants |
| Race/Ethnicity, Customized Race-Not Collected | 41 Participants | 9 Participants | 6 Participants | 1 Participants | 25 Participants |
| Race/Ethnicity, Customized Race-Other | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Race-White | 25 Participants | 3 Participants | 2 Participants | 6 Participants | 14 Participants |
| Sex: Female, Male Female | 23 Participants | 7 Participants | 4 Participants | 3 Participants | 9 Participants |
| Sex: Female, Male Male | 47 Participants | 5 Participants | 5 Participants | 6 Participants | 31 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 23 / 40 | 4 / 9 | 4 / 9 | 6 / 12 |
| other Total, other adverse events | 40 / 40 | 9 / 9 | 9 / 9 | 12 / 12 |
| serious Total, serious adverse events | 31 / 40 | 5 / 9 | 6 / 9 | 9 / 12 |
Outcome results
Primary
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/Cubic Millimeter(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.
Time frame: Day 1 Week 1 up to Week 3
Population: Dose-Limiting Toxicity Analysis (DLT) Set included all participants who received at least 90 percent (%) of the bintrafusp alfa infusion and all other planned study administrations during the DLT observation period of 3 weeks and who did not discontinue the study for other reasons than DLT during the first cycle, or who experienced at least one DLT.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | Number of Participants With Dose-Limiting Toxicities (DLTs) | 1 Participants |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | Number of Participants With Dose-Limiting Toxicities (DLTs) | 1 Participants |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | Number of Participants With Dose-Limiting Toxicities (DLTs) | 0 Participants |
| Cohort D: Bintrafusp Alfa + Docetaxel | Number of Participants With Dose-Limiting Toxicities (DLTs) | 3 Participants |
Primary
Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether considered related to the medicinal product or protocol-specified procedure. 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. TEAE was defined as events with onset date or worsening during the on-treatment period. TEAEs included serious TEAEs and non-serious TEAEs.
Time frame: Time from first treatment assessed up to approximately 26 months
Population: The safety analysis set (SAF) included all participants who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies).
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 40 Participants |
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 31 Participants |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 5 Participants |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 9 Participants |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 9 Participants |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 6 Participants |
| Cohort D: Bintrafusp Alfa + Docetaxel | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 12 Participants |
| Cohort D: Bintrafusp Alfa + Docetaxel | Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 9 Participants |
Secondary
Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa
The AUC from time zero (dosing time) extrapolated to infinity, based on the predicted value for the concentration at tlast, as estimated using the linear regression from terminal first order (elimination) rate constant determination. AUC0-inf= AUC0-tlast +Clast pred/ terminal first order (elimination) rate constant.
Time frame: Predose, Day 22, Day 43, Day 64 and Day 85
Population: In the context of Study NCT03631706, NCT04066491, and NCT03840902 been terminated prematurely, the sponsor decided to restrict the analyses of Pharmacokinetics (PK) Parameter and no PK data was collected.
Secondary
Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa
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).
Time frame: Predose, Day 22, Day 43, Day 64 and Day 85
Population: In the context of Study NCT03631706, NCT04066491, and NCT03840902 been terminated prematurely, the sponsor decided to restrict the analyses of Pharmacokinetics (PK) Parameter and no PK data was collected.
Secondary
Duration of Response (DOR)
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. Results were calculated based on Kaplan-Meier estimates.
Time frame: Time from first documentation of a confirmed objective response to PD or death due to any cause (assessed up to approximately 26 months)
Population: The full analysis set (FAS) included all participants who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | Duration of Response (DOR) | 9.6 months |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | Duration of Response (DOR) | NA months |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | Duration of Response (DOR) | 10.5 months |
| Cohort D: Bintrafusp Alfa + Docetaxel | Duration of Response (DOR) | 3.4 months |
Secondary
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa
Ceoi was the observed concentration at the end of the infusion period. This was taken directly from the observed Bintrafusp Alfa concentration-time data.
Time frame: Predose, Day 22, Day 43, Day 64 and Day 85
Population: In the context of Study NCT03631706, NCT04066491, and NCT03840902 been terminated prematurely, the sponsor decided to restrict the analyses of Pharmacokinetics (PK) Parameter and no PK data was collected.
Secondary
Maximum Observed Plasma Concentration (Cmax) of Bintrafusp Alfa
Cmax was obtained directly from the concentration versus time curve.
Time frame: Predose, Day 22, Day 43, Day 64 and Day 85
Population: In the context of Study NCT03631706, NCT04066491, and NCT03840902 been terminated prematurely, the sponsor decided to restrict the analyses of Pharmacokinetics (PK) Parameter and no PK data was collected.
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 assessed up to approximately 26 months
Population: Immunogenicity Analysis Set included all participants who have received at least of 1 dose of bintrafusp alfa + chemotherapy and had at least 1 valid antidrug antibody result.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | Number of Participants With Positive Antidrug Antibodies (ADA) | 9 Participants |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | Number of Participants With Positive Antidrug Antibodies (ADA) | 3 Participants |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | Number of Participants With Positive Antidrug Antibodies (ADA) | 2 Participants |
| Cohort D: Bintrafusp Alfa + Docetaxel | Number of Participants With Positive Antidrug Antibodies (ADA) | 3 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 treatment assessed up to approximately 26 months
Population: The full analysis set (FAS) included all participants who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | Overall Survival (OS) | 11.4 months |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | Overall Survival (OS) | 11.8 months |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | Overall Survival (OS) | NA months |
| Cohort D: Bintrafusp Alfa + Docetaxel | Overall Survival (OS) | 16.5 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 Investigator (IRC)
Percentage of participants with confirmed objective response that is at least one overall assessment of complete response (CR) or partial response (PR) reported here. 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 assessed up to approximately 26 months
Population: The full analysis set (FAS) included all participants who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator (IRC) | 45.0 Percentage of Participants |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator (IRC) | 66.7 Percentage of Participants |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator (IRC) | 44.4 Percentage of Participants |
| Cohort D: Bintrafusp Alfa + Docetaxel | Percentage of Participants With Confirmed Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) as Assessed by Investigator (IRC) | 16.7 Percentage of Participants |
Secondary
Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
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 approximately 26 months
Population: The full analysis set (FAS) included all participants who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies)
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed | Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator | 5.0 months |
| Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel | Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator | 4.1 months |
| Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine | Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator | 5.4 months |
| Cohort D: Bintrafusp Alfa + Docetaxel | Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator | 2.6 months |
Secondary
Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa
Ctrough was the serum concentration observed immediately before next dosing.
Time frame: Predose, Day 22, Day 43, Day 64 and Day 85
Population: In the context of Study NCT03631706, NCT04066491, and NCT03840902 been terminated prematurely, the sponsor decided to restrict the analyses of Pharmacokinetics (PK) Parameter and no PK data was collected.
Secondary
Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa
Elimination half-life determined as 0.693/terminal first order (elimination) rate constant.
Time frame: Predose, Day 22, Day 43, Day 64 and Day 85
Population: In the context of Study NCT03631706, NCT04066491, and NCT03840902 been terminated prematurely, the sponsor decided to restrict the analyses of Pharmacokinetics (PK) Parameter and no PK data was collected.
Secondary
Time to Reach Maximum Plasma Concentration (Tmax) of Bintrafusp Alfa
The time to reach the maximum observed concentration collected during a dosing interval. Tmax was obtained directly from the concentration versus time curve.
Time frame: Predose, Day 22, Day 43, Day 64 and Day 85
Population: In the context of Study NCT03631706, NCT04066491, and NCT03840902 been terminated prematurely, the sponsor decided to restrict the analyses of Pharmacokinetics (PK) Parameter and no PK data was collected.