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

NCT ID: NCT03840915

Last Updated: 2023-08-21

Study Results

Results available

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1/PHASE2

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-04-02

Study Completion Date

2022-07-29

Brief Summary

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

Detailed Description

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Conditions

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Carcinoma, Non-Small-Cell Lung

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Cohort A: Cisplatin or Carboplatin + Pemetrexed + Bintrafusp alfa

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.

Group Type EXPERIMENTAL

Cisplatin

Intervention Type 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).

Carboplatin

Intervention Type 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).

Pemetrexed

Intervention Type DRUG

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

M7824

Intervention Type 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 B: Carboplatin + Paclitaxel or Nab-paclitaxel + 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.

Group Type EXPERIMENTAL

Nab-paclitaxel

Intervention Type 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).

Carboplatin

Intervention Type DRUG

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).

Bintrafusp alfa

Intervention Type 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.

Paclitaxel

Intervention Type 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 C: Cisplatin or Carboplatin + Gemcitabine + 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.

Group Type EXPERIMENTAL

Cisplatin

Intervention Type 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).

Gemcitabine

Intervention Type 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).

Carboplatin

Intervention Type DRUG

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).

Bintrafusp alfa

Intervention Type 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 D: Docetaxel + Bintrafusp alfa

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

Group Type EXPERIMENTAL

Docetaxel

Intervention Type 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).

Bintrafusp alfa

Intervention Type 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.

Interventions

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Cisplatin

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).

Intervention Type DRUG

Carboplatin

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).

Intervention Type DRUG

Pemetrexed

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

Intervention Type DRUG

Nab-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).

Intervention Type DRUG

Gemcitabine

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).

Intervention Type DRUG

Docetaxel

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).

Intervention Type DRUG

M7824

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.

Intervention Type DRUG

Carboplatin

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).

Intervention Type DRUG

Carboplatin

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).

Intervention Type DRUG

Bintrafusp 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.

Intervention Type DRUG

Paclitaxel

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).

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role collaborator

EMD Serono Research & Development Institute, Inc.

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Medical Responsible

Role: STUDY_DIRECTOR

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

Locations

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

Fountain Valley, California, United States

Site Status

California Cancer Associates for Research & Excellence, Inc.

San Marcos, California, United States

Site Status

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

Port Saint Lucie, Florida, United States

Site Status

Baptist Health Lexington Oncology Associates

Lexington, Kentucky, United States

Site Status

University of Maryland - DUPLICATE/Pediatric Surgery

Baltimore, Maryland, United States

Site Status

RCCA MD LLC - Bethesda

Bethesda, Maryland, United States

Site Status

Henry Ford Health System

Detroit, Michigan, United States

Site Status

Vanderbilt University Medical Center

Nashville, Tennessee, United States

Site Status

Universitair Ziekenhuis Brussel - Geriatrie

Brussels, , Belgium

Site Status

UZ Antwerpen

Edegem, , Belgium

Site Status

Universitair Ziekenhuis Gent - Medical Oncology

Ghent, , Belgium

Site Status

CHU Sart Tilman

Liège, , Belgium

Site Status

AZ Sint-Maarten

Mechelen, , Belgium

Site Status

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

Bordeaux, , France

Site Status

Centre Georges François Leclerc - Unité de Phase I

Dijon, , France

Site Status

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

Marseille, , France

Site Status

ICO - Site René Gauducheau

Nantes, , France

Site Status

Centre Antoine Lacassagne

Nice, , France

Site Status

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

Poitiers, , France

Site Status

Countries

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United States Belgium France

References

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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.

Reference Type DERIVED
PMID: 36066618 (View on PubMed)

Provided Documents

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Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

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https://medical.emdserono.com/en_US/home.html

US Medical Information website, Medical Resources

Other Identifiers

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2018-004040-28

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS200647_0024

Identifier Type: -

Identifier Source: org_study_id

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