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

Sponsor

EMD Serono Research & Development Institute, Inc. (Industry)

Overall Status

Completed

CT.gov ID

NCT03840915

Collaborator

Merck KGaA, Darmstadt, Germany (Industry)

Enrollment

Locations

Arms

39.9

Actual Duration (Months)

3.7

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Non-Small-Cell Lung	Drug: Cisplatin Drug: Carboplatin Drug: Pemetrexed Drug: Nab-paclitaxel Drug: Gemcitabine Drug: Docetaxel Drug: M7824 Drug: Carboplatin Drug: Carboplatin Drug: M7824 Drug: Paclitaxel	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

70 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Apr 2, 2019

Actual Primary Completion Date :

Jul 29, 2022

Actual Study Completion Date :

Jul 29, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Cohort A: Cisplatin or Carboplatin + Pemetrexed + M7824	Drug: Cisplatin Cisplatin will be 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). Drug: Carboplatin Carboplatin will be 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). Drug: Pemetrexed Pemetrexed will be administered intravenously at a dose of 500 mg/ m^2 over 10 minutes every 21 days. Drug: M7824 M7824 will be 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.
Experimental: Cohort B: Carboplatin + Paclitaxel or Nab-paclitaxel + M7824	Drug: Nab-paclitaxel Nab-paclitaxel will be 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). Drug: Carboplatin Carboplatin will be 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). Drug: M7824 M7824 will be 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. Drug: Paclitaxel Paclitaxel will be administered intravenously at a dose of 200 mg/m2 over 3 hours every 3 weeks for 4 cycles (each cycle is 21 days).
Experimental: Cohort C: Cisplatin or Carboplatin + Gemcitabine + M7824	Drug: Cisplatin Cisplatin will be 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). Drug: Gemcitabine Gemcitabine will be 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). Drug: Carboplatin Carboplatin will be 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). Drug: M7824 M7824 will be 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.
Experimental: Cohort D: Docetaxel + M7824	Drug: Docetaxel Docetaxel will be administered intravenously at a dose of 75 mg/m^2 over 60 minutes every 21 days for 4 cycles (each cycle is 21 days). Drug: M7824 M7824 will be 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.

Outcome Measures

Primary Outcome Measures

Incidence of Dose Limiting Toxicities (DLTs) [Day 1 to Day 21 (Cycle 1)]
Incidence of Treatment Emergent Adverse Events (TEAEs) and Treatment Related Adverse Events [Up to 3 years]

Secondary Outcome Measures

Confirmed Objective Response as Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 [Up to 3 years]
Progression-Free Survival (PFS) as Assessed by Investigator According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 [Up to 3 years]
Overall Survival (OS) [Up to 3 years]
Duration of Response (DOR) According to Response Evaluation Criteria in Solid Tumors Version (RECIST) 1.1 [Up to 3 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Compassionate Care Research Group Inc - Edinger Medical Group, Inc.	Fountain Valley	California	United States	92708
2	California Cancer Associates for Research & Excellence, Inc.	San Marcos	California	United States	92069
3	Hematology - Oncology Associates of Treasure Coast - Hematology-Oncology Associates of Treasure Coast	Port Saint Lucie	Florida	United States	34952
4	Baptist Health Lexington Oncology Associates	Lexington	Kentucky	United States	40503
5	University of Maryland - DUPLICATE/Pediatric Surgery	Baltimore	Maryland	United States	21201
6	RCCA MD LLC - Bethesda	Bethesda	Maryland	United States	20817
7	Henry Ford Health System	Detroit	Michigan	United States	48202
8	Vanderbilt University Medical Center	Nashville	Tennessee	United States	37232-8805
9	Universitair Ziekenhuis Brussel - Geriatrie	Bruxelles		Belgium
10	UZ Antwerpen	Edegem		Belgium
11	Universitair Ziekenhuis Gent - Medical Oncology	Gent		Belgium
12	CHU Sart Tilman	Liège		Belgium
13	AZ Sint-Maarten	Mechelen		Belgium
14	Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Maison du Ha	Bordeaux cedex		France
15	Centre Georges François Leclerc - Unité de Phase I	Dijon cedex		France
16	Hôpital de la Timone# - CPCEM CIC - Bat F 1er étage	Marseille cedex 5		France
17	ICO - Site René Gauducheau	Nantes Cedex 01		France
18	Centre Antoine Lacassagne	Nice cedex 02		France
19	CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale	Poitiers Cedex		France