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

NCT03840915 | Completed Phase 1 Results DMC FDA Drug

• 2 other identifiers: MS200647_00242018-004040-28
• Study Type: interventional
• Target: 70
• Locations: 3 countries
• Sites: 19

Brief Summary

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

Conditions

Carcinoma, Non-Small-Cell Lung

Keywords

Non-small Cell Lung Cancer; Bintrafusp alfa (proposed INN); M7824; Stage IV; INTR@PID LUNG 024

Outcome Measures

Primary Outcomes (2)

• 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.

  Day 1 Week 1 up to Week 3

• 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 from first treatment assessed up to approximately 26 months

Secondary Outcomes (12)

• 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

• 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

• Overall Survival (OS)

  Time from first treatment assessed up to approximately 26 months

• 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)

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

  Predose, Day 22, Day 43, Day 64 and Day 85

Study Arms (4)

Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa

EXPERIMENTAL

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.

Drug: Cisplatin; Drug: Carboplatin; Drug: Pemetrexed; Drug: M7824

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

EXPERIMENTAL

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.

Drug: Nab-paclitaxel; Drug: Carboplatin; Drug: Bintrafusp alfa; Drug: Paclitaxel

Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa

EXPERIMENTAL

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.

Drug: Cisplatin; Drug: Gemcitabine; Drug: Carboplatin; Drug: Bintrafusp alfa

Cohort D: Docetaxel + Bintrafusp alfa

EXPERIMENTAL

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

Drug: Docetaxel; Drug: Bintrafusp alfa

Interventions

Cisplatin DRUG

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).

Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa; Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa

Carboplatin DRUG

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).

Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa

Pemetrexed DRUG

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

Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa

Nab-paclitaxel DRUG

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).

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

Gemcitabine DRUG

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).

Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa

Docetaxel DRUG

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).

Cohort D: Docetaxel + Bintrafusp alfa

M7824 DRUG

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.

Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa

Bintrafusp alfa DRUG

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.

Cohort B: Carboplatin + Paclitaxel or Nab-paclitaxel + Bintrafusp alfa; Cohort C: Cisplatin or Carboplatin + Gemcitabine + Bintrafusp alfa; Cohort D: Docetaxel + Bintrafusp alfa

Paclitaxel DRUG

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).

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

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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:
• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• EMD Serono Research & Development Institute, Inc.: lead
• Merck KGaA, Darmstadt, Germany: collaborator

Study Sites (19)

Compassionate Care Research Group Inc - Edinger Medical Group, Inc.

Fountain Valley, California, 92708, United States

Location

California Cancer Associates for Research & Excellence, Inc.

San Marcos, California, 92069, United States

Location

Hematology - Oncology Associates of Treasure Coast - Hematology-Oncology Associates of Treasure Coast

Port Saint Lucie, Florida, 34952, United States

Location

Baptist Health Lexington Oncology Associates

Lexington, Kentucky, 40503, United States

Location

University of Maryland - DUPLICATE/Pediatric Surgery

Baltimore, Maryland, 21201, United States

Location

RCCA MD LLC - Bethesda

Bethesda, Maryland, 20817, United States

Location

Henry Ford Health System

Detroit, Michigan, 48202, United States

Location

Vanderbilt University Medical Center

Nashville, Tennessee, 37232-8805, United States

Location

Universitair Ziekenhuis Brussel - Geriatrie

Brussels, Belgium

Location

UZ Antwerpen

Edegem, Belgium

Location

Universitair Ziekenhuis Gent - Medical Oncology

Ghent, Belgium

Location

CHU Sart Tilman

Liège, Belgium

Location

AZ Sint-Maarten

Mechelen, Belgium

Location

Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Maison du Ha

Bordeaux, France

Location

Centre Georges François Leclerc - Unité de Phase I

Dijon, France

Location

Hôpital de la Timone# - CPCEM CIC - Bat F 1er étage

Marseille, France

Location

ICO - Site René Gauducheau

Nantes, France

Location

Centre Antoine Lacassagne

Nice, France

Location

CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale

Poitiers, France

Location

Related Publications (1)

• Vugmeyster Y, Grisic AM, Wilkins JJ, Loos AH, Hallwachs R, Osada M, Venkatakrishnan K, Khandelwal A. Model-informed approach for risk management of bleeding toxicities for bintrafusp alfa, a bifunctional fusion protein targeting TGF-beta and PD-L1. Cancer Chemother Pharmacol. 2022 Oct;90(4):369-379. doi: 10.1007/s00280-022-04468-6. Epub 2022 Sep 6.

  PMID: 36066618 DERIVED

Related Links

• Trial Awareness and Transparency website
• US Medical Information website, Medical Resources

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Cisplatin; Carboplatin; Pemetrexed; 130-nm albumin-bound paclitaxel; Gemcitabine; Docetaxel; bintrafusp alfa protein, human; Paclitaxel

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Results Point of Contact

• Title: Communication Center
• Organization: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 12, 2019
• First Posted: February 15, 2019
• Study Start: April 2, 2019
• Primary Completion: July 29, 2022
• Study Completion: July 29, 2022
• Last Updated: August 21, 2023
• Results First Posted: August 21, 2023

Record last verified: 2023-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, CSR
• Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.

Locations

FR (6); BE (5); US (8)