Clinical trial NCT03840915: M7824 in Combination With Chemotherapy in Stage IV Non-small Cell Lung Cancer (NSCLC)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Carcinoma, Non-Small-Cell Lung
Keywords: Non-small Cell Lung Cancer
Bintrafusp alfa (proposed INN)
M7824
Stage IV
INTR@PID LUNG 024
Lead sponsor: EMD Serono
Sponsor class: INDUSTRY
Collaborators: name: Merck KGaA, Darmstadt, Germany
First posted: 2019-02-15
Enrollment: 70
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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


Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants With Dose-Limiting Toxicities (DLTs)
timeFrame: Day 1 Week 1 up to Week 3
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs
timeFrame: Time from first treatment assessed up to approximately 26 months
Secondary outcomes:
measure: 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)
timeFrame: Time from first treatment assessed up to approximately 26 months
measure: Progression-Free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST Version 1.1) Assessed by Investigator
timeFrame: Time from first administration of study drug until the first documentation of PD or death, assessed up to approximately 26 months
measure: Overall Survival (OS)
timeFrame: Time from first treatment assessed up to approximately 26 months
measure: Duration of Response (DOR)
timeFrame: Time from first documentation of a confirmed objective response to PD or death due to any cause (assessed up to approximately 26 months)
measure: Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Bintrafusp Alfa
timeFrame: Predose, Day 22, Day 43, Day 64 and Day 85
measure: Serum Trough Concentration Levels (Ctrough) of Bintrafusp Alfa
timeFrame: Predose, Day 22, Day 43, Day 64 and Day 85
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to Last Measurable Concentration (AUC0-t) of Bintrafusp Alfa
timeFrame: Predose, Day 22, Day 43, Day 64 and Day 85
measure: Area Under the Plasma Concentration-time Curve From Time Zero Extrapolated to Infinity (AUC0-inf) of Bintrafusp Alfa
timeFrame: Predose, Day 22, Day 43, Day 64 and Day 85
measure: Maximum Observed Plasma Concentration (Cmax) of Bintrafusp Alfa
timeFrame: Predose, Day 22, Day 43, Day 64 and Day 85
measure: Time to Reach Maximum Plasma Concentration (Tmax) of Bintrafusp Alfa
timeFrame: Predose, Day 22, Day 43, Day 64 and Day 85
measure: Terminal Elimination Half-Life (T1/2) of Bintrafusp Alfa
timeFrame: Predose, Day 22, Day 43, Day 64 and Day 85
measure: Number of Participants With Positive Antidrug Antibodies (ADA)
timeFrame: Time from first treatment assessed up to approximately 26 months
Other outcomes:
Locations:
city: Fountain Valley
country: United States
facility: Compassionate Care Research Group Inc - Edinger Medical Group, Inc.
state: California
city: San Marcos
country: United States
facility: California Cancer Associates for Research & Excellence, Inc.
state: California
city: Port Saint Lucie
country: United States
facility: Hematology - Oncology Associates of Treasure Coast - Hematology-Oncology Associates of Treasure Coast
state: Florida
city: Lexington
country: United States
facility: Baptist Health Lexington Oncology Associates
state: Kentucky
city: Baltimore
country: United States
facility: University of Maryland - DUPLICATE/Pediatric Surgery
state: Maryland
city: Bethesda
country: United States
facility: RCCA MD LLC - Bethesda
state: Maryland
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
city: Bruxelles
country: Belgium
facility: Universitair Ziekenhuis Brussel - Geriatrie
city: Edegem
country: Belgium
facility: UZ Antwerpen
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent - Medical Oncology
city: Liège
country: Belgium
facility: CHU Sart Tilman
city: Mechelen
country: Belgium
facility: AZ Sint-Maarten
city: Bordeaux cedex
country: France
facility: Groupe Hospitalier Sud - Hôpital Haut-Lévêque - Maison du Ha
city: Dijon cedex
country: France
facility: Centre Georges François Leclerc - Unité de Phase I
city: Marseille cedex 5
country: France
facility: Hôpital de la Timone# - CPCEM CIC - Bat F 1er étage
city: Nantes Cedex 01
country: France
facility: ICO - Site René Gauducheau
city: Nice cedex 02
country: France
facility: Centre Antoine Lacassagne
city: Poitiers Cedex
country: France
facility: CHU Poitiers - Hôpital la Milétrie - service d'oncologie médicale
Study officials:
affiliation: Merck Healthcare KGaA, Darmstadt, Germany, an affiliate of Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References:
citation: 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.