M7824 in Combination With Chemotherapy in Stage IV Non-small Cell Lung Cancer (NSCLC)
- Conditions
- Carcinoma, Non-Small-Cell Lung
- Interventions
- Registration Number
- NCT03840915
- Brief Summary
The main purpose of the study was to evaluate the safety and tolerability of M7824 in combination with chemotherapy.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 70
-
Participants greater than or equals to (>=) 18 years of age inclusive at the time of signing the informed consent
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Participants who have histologically confirmed diagnosis of Stage IV NSCLC:
- Participants in Cohort A, B, and C must not have received prior systemic therapy treatment for their Stage IV NSCLC
- 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
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa Cisplatin Participants received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin or Carboplatin, and Pemetrexed every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa Carboplatin Participants received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin or Carboplatin, and Pemetrexed every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa Gemcitabine Participants received 2400 mg Bintrafusp alfa along with Cisplatin or Carboplatin, and Gemcitabine every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa M7824 Participants received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin or Carboplatin, and Pemetrexed every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort B: Carboplatin + Paclitaxel or Nab-paclitaxel + Bintrafusp alfa Bintrafusp alfa Participants received 2400 mg Bintrafusp alfa along with Carboplatin, and Paclitaxel or Nab-paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort D: Docetaxel + Bintrafusp alfa Docetaxel Participants received 2400 mg Bintrafusp alfa along with Docetaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort D: Docetaxel + Bintrafusp alfa Bintrafusp alfa Participants received 2400 mg Bintrafusp alfa along with Docetaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort B: Carboplatin + Paclitaxel or Nab-paclitaxel + Bintrafusp alfa Nab-paclitaxel Participants received 2400 mg Bintrafusp alfa along with Carboplatin, and Paclitaxel or Nab-paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa Pemetrexed Participants received 2400 miligrams (mg) Bintrafusp alfa along with Cisplatin or Carboplatin, and Pemetrexed every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort B: Carboplatin + Paclitaxel or Nab-paclitaxel + Bintrafusp alfa Paclitaxel Participants received 2400 mg Bintrafusp alfa along with Carboplatin, and Paclitaxel or Nab-paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort B: Carboplatin + Paclitaxel or Nab-paclitaxel + Bintrafusp alfa Carboplatin Participants received 2400 mg Bintrafusp alfa along with Carboplatin, and Paclitaxel or Nab-paclitaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa Cisplatin Participants received 2400 mg Bintrafusp alfa along with Cisplatin or Carboplatin, and Gemcitabine every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa Bintrafusp alfa Participants received 2400 mg Bintrafusp alfa along with Cisplatin or Carboplatin, and Gemcitabine every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death. Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa Carboplatin Participants received 2400 mg Bintrafusp alfa along with Cisplatin or Carboplatin, and Gemcitabine every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
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.
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.
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.
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).
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.
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.
Trial Locations
- Locations (19)
Compassionate Care Research Group Inc - Edinger Medical Group, Inc.
🇺🇸Fountain Valley, California, United States
RCCA MD LLC - Bethesda
🇺🇸Bethesda, Maryland, United States
University of Maryland - DUPLICATE/Pediatric Surgery
🇺🇸Baltimore, Maryland, United States
Hematology - Oncology Associates of Treasure Coast - Hematology-Oncology Associates of Treasure Coast
🇺🇸Port Saint Lucie, Florida, United States
Baptist Health Lexington Oncology Associates
🇺🇸Lexington, Kentucky, United States
Vanderbilt University Medical Center
🇺🇸Nashville, Tennessee, United States
Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Maison du Ha
🇫🇷Bordeaux cedex, France
ICO - Site René Gauducheau
🇫🇷Nantes Cedex 01, France
Centre Antoine Lacassagne
🇫🇷Nice cedex 02, France
CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale
🇫🇷Poitiers Cedex, France
California Cancer Associates for Research & Excellence, Inc.
🇺🇸San Marcos, California, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Universitair Ziekenhuis Brussel - Geriatrie
🇧🇪Bruxelles, Belgium
CHU Sart Tilman
🇧🇪Liège, Belgium
Hôpital de la Timone# - CPCEM CIC - Bat F 1er étage
🇫🇷Marseille cedex 5, France
Centre Georges François Leclerc - Unité de Phase I
🇫🇷Dijon cedex, France
UZ Antwerpen
🇧🇪Edegem, Belgium
Universitair Ziekenhuis Gent - Medical Oncology
🇧🇪Gent, Belgium
AZ Sint-Maarten
🇧🇪Mechelen, Belgium