Neoplasms

All Conditions

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Micronutrients

Hematinics

Vitamins

Gemcitabine

Paclitaxel

Docetaxel

Albumin-Bound Paclitaxel

Carboplatin

Pemetrexed

Cisplatin

Tubulin Modulators

Antimitotic Agents

Antimetabolites

Enzyme Inhibitors

Folic Acid

Vitamin B Complex

Folic Acid Antagonists

Folinic Acid

Folate

Vitamin B9

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.

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.

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.

Participants received 2400 mg Bintrafusp alfa along with Docetaxel every 3 weeks until confirmed disease progression, unacceptable toxicity, study withdrawal or death.

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).

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).

Pemetrexed was administered intravenously at a dose of 500 mg/ m\^2 over 10 minutes every 21 days.

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).

Nab-paclitaxel

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).

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).

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.

M7824

Carboplatin was administered at area under the concentration-time Curve (AUC) 6 when combined with nab-paclitaxel over 30 to 60 minutes every 21 days for 4 cycles (each cycle is 21 days).

Carboplatin was administered at area under the concentration-time Curve (AUC) 5 when combined with gemcitabine over 30 to 60 minutes every 21 days for 4 cycles (each cycle is 21 days).

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.

Bintrafusp alfa

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).

Medical Responsible

The main purpose of the study was to evaluate the safety and tolerability of M7824 in combination with chemotherapy.

M7824 in Combination With Chemotherapy in Stage IV Non-small Cell Lung Cancer (NSCLC)

A Phase Ib/II, Open-Label Study of M7824 in Combination With Chemotherapy in Participants With Stage IV Non-small Cell Lung Cancer

We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21

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.

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.

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.

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.

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.

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.

Ceoi was the observed concentration at the end of the infusion period. This was taken directly from the observed Bintrafusp Alfa concentration-time data.

Ctrough was the serum concentration observed immediately before next dosing.

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).

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.

Cmax was obtained directly from the concentration versus time curve.

The time to reach the maximum observed concentration collected during a dosing interval. Tmax was obtained directly from the concentration versus time curve.

Elimination half-life determined as 0.693/terminal first order (elimination) rate constant.

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.

Merck KGaA, Darmstadt, Germany

EMD Serono Research & Development Institute, Inc.

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.

Cohort A: Bintrafusp Alfa + Cisplatin/Carboplatin + Pemetrexed

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.

Cohort B: Bintrafusp Alfa + Carboplatin + Paclitaxel or Nab-paclitaxel

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.

Cohort C: Bintrafusp Alfa + Cisplatin/Carboplatin + Gemcitabine

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.

Cohort D: Bintrafusp Alfa + Docetaxel

Total

Age, Continuous

Sex: Female, Male

Ethnicity-Not Hispanic or Latino

Ethnicity-Unknown or Not Reported

Race-Black or African American

Race-White

Race-Other

Race-Not Collected

Race/Ethnicity, Customized

Communication Center

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.

Number of Participants With Dose-Limiting Toxicities (DLTs)

TEAEs

Serious TEAEs

The safety analysis set (SAF) included all participants who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies).

Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs

The full analysis set (FAS) included all participants who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies).

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)

The full analysis set (FAS) included all participants who were administered any dose of any study intervention (bintrafusp alfa or one of the chemotherapies)

Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator

Overall Survival (OS)

Duration of Response (DOR)

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.

Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa

Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa

Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa

Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa

Maximum Observed Plasma Concentration (Cmax) of Bintrafusp Alfa

Time to Reach Maximum Plasma Concentration (Tmax) of Bintrafusp Alfa

Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa

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.

Spots Global Cancer Trial Database for M7824 in Combination With Chemotherapy in Stage IV Non-small Cell Lung Cancer (NSCLC)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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