KEYMAKER-U01 Substudy 01A: Efficacy and Safety Study of P... | NCT04165070

NCT04165070

ID	Type	Description
MK-3475-01A	Other Identifier	MSD
KEYMAKER-U01A	Other Identifier	MSD
2023-506932-33-00	Registry Identifier	EU CT
U1111-1294-6474	Registry Identifier	UTN
2020-001626-56	EudraCT Number

Status Module

Name	Class
Daiichi Sankyo	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Part A: Pembrolizumab+Vibostolimab+Carboplatin + Paclitaxel	Experimental	On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg intravenously (IV) PLUS vibostolimab IV PLUS carboplatin Area Under the Concentration-Time Curve (AUC) 6 IV PLUS paclitaxel 200 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).	Biological: Pembrolizumab Drug: Carboplatin Drug: Paclitaxel Biological: Vibostolimab
Part A: Pembrolizumab+Vibostolimab+Carboplatin + Pemetrexed	Experimental	On Day 1 of each 3-week cycle, participants with nonsquamous NSCLC receive pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS carboplatin AUC 5 IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV PLUS vibostolimab IV PLUS pemetrexed 500 mg/m^2 IV in Cycles 5-35 (total treatment duration: up to approximately 2 years).	Biological: Pembrolizumab Drug: Carboplatin Drug: Pemetrexed Biological: Vibostolimab
Part A: Pembrolizumab+Boserolimab+Carboplatin+Paclitaxel	Experimental	On Day 1 of each 3-week cycle, participants with squamous NSCLC receive pembrolizumab 200 mg IV PLUS carboplatin AUC 6 IV PLUS paclitaxel 200 mg/m^2 IV PLUS boserolimab IV on Day 1 every 6 weeks (every other 3-week cycle) (Q6W) in Cycles 1-4, followed by maintenance treatment of pembrolizumab 200 mg IV Q3W PLUS boserolimab IV Q6W from Cycles 5 up to Cycle 35 (total treatment duration: up to approximately 2 years).	Biological: Pembrolizumab Drug: Carboplatin

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Pembrolizumab	Biological	IV infusion	Part A: Pembrolizumab+Boserolimab+Carboplatin+Paclitaxel Part A: Pembrolizumab+Boserolimab+Carboplatin+Pemetrexed

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Part A: Objective Response Rate (ORR) According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)	ORR was defined as the percentage of participants in the analysis population who had a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: ≥30% decrease in the sum of diameters of target lesions) per RECIST 1.1. ORR will be reported.	Up to approximately 24 months
Part B: Number of Participants Who Experience One or More Adverse Events (AEs)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who experience an AE will be reported.	Up to approximately 27 months
Part B: Number of Participants Who Discontinue Study Intervention Due to an Adverse Event (AE)	An AE is defined as any unfavorable and unintended sign, symptom, disease, or worsening of preexisting condition temporally associated with study treatment and irrespective of causality to study treatment. The number of participants who discontinue study intervention due to an AE will be reported.	Up to approximately 24 months
Part B: Number of Participants Who Experience a Dose Limiting Toxicity (DLT)	A DLT is defined as an event with toxicity including the type, severity, time of onset, time of resolution, and the probable association with study treatment that are not due to pre-existing conditions as defined by the Common Terminology Criteria for Adverse Events Version 5.0 (CTCAE 5.0). Number of participants who experience a DLT per CTCAE 5.0 will be reported.	Up to approximately 3 Weeks

Secondary Outcomes

Measure	Description	Time Frame
Part A: Progression-Free Survival (PFS) According to RECIST 1.1	PFS is defined as the time from first dose of study treatment until either the earliest date of documented progressive disease (PD) or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS will be reported.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

The main inclusion criteria include but are not limited to the following:

Has histologically- or cytologically-confirmed diagnosis of Stage IV squamous or nonsquamous NSCLC
Participants with nonsquamous NSCLC who are not eligible for an approved targeted therapy
Is able to provide archival tumor tissue sample collected either within 5 years or within the interval from completion of last treatment but before entering the screening period or newly obtained core or excisional biopsy of a tumor lesion not previously irradiated obtained within 90 days of treatment initiation
Has not received prior systemic treatment for their metastatic NSCLC
Is able to complete all screening procedures within the 35-day screening window for Part A and 28-day screening window for Part B

Exclusion Criteria:

The main exclusion criteria include but are not limited to the following:

Has a diagnosis of small cell lung cancer
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days before the first dose of study treatment
Has a known additional malignancy that is progressing or has required active treatment within the past 2 years
Has known active central nervous system (CNS) metastases and/or carcinomatous meningitis
Has an active autoimmune disease that has required systemic treatment in the past 2 years
Has a history of (noninfectious) pneumonitis that required steroids or has current pneumonitis
Has an active infection requiring systemic therapy
Has clinically significant cardiac disease, including unstable angina, acute myocardial infarction within 6 months from Day 1 of study treatment administration, or New York Heart Association Class III or IV congestive heart failure
Has a known history of human immunodeficiency virus (HIV) infection. Well-controlled HIV with anti-retroviral therapy (ART) is not excluded
Has a known history of Hepatitis B (HPV) or known active Hepatitis C virus infection. Hepatitis B surface antigen (HBsAg) positive is eligible if on HBV antiviral therapy for at least 4 weeks and HBV viral load is undetectable prior to randomization
Has had major surgery <3 weeks before the first dose of study treatment
Is expected to require any other form of antineoplastic therapy while on study
Has a history or current evidence of a gastrointestinal (GI) condition (e.g. inflammatory bowel disease, Crohn's disease, ulcerative colitis) or impaired liver function or diseases that in the opinion of the investigator may significantly alter the absorption or metabolism of oral medications
Is getting chemotherapy and has clinically active diverticulitis, intra-abdominal abscess, GI obstruction, or peritoneal carcinomatosis
Has preexisting neuropathy that is moderate in intensity
Has received prior systemic cytotoxic chemotherapy or other targeted or biological antineoplastic therapy for metastatic disease
Is unable or unwilling to take folic acid or vitamin B12 supplementation, for participants who will receive pemetrexed
Has a known sensitivity to any component of carboplatin, paclitaxel, pemetrexed or any of their excipients
Has received prior radiation therapy to the lung that is >30 Gray (Gy) within 6 months of the first dose of study treatment
Has received a live vaccine within 30 days before the first dose of study treatment. Any licensed COVID-19 vaccine (including for Emergency Use) in a particular country is allowed as long as they are messenger ribonucleic acid (mRNA) vaccines, adenoviral vaccines, or inactivated vaccines. Investigational vaccines (ie, those not licensed or approved for Emergency Use) are not allowed
Has received any prior immunotherapy and was discontinued from that treatment due to a severe or worse immune-related adverse event (irAE)
Has had chemotherapy or biological cancer therapy within 4 weeks before the first dose of study treatment or has not recovered to Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 or better from the AEs due to cancer therapeutics administered more than 4 weeks before the first dose of study treatment (including participants who had previous immunomodulatory therapy with residual irAEs)
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study treatment
Previously had a severe hypersensitivity reaction to treatment with monoclonal antibodies (including pembrolizumab) and/or any of their excipients
Has had an allogenic tissue/solid organ transplant

Label	URL
Merck Clinical Trials Information	View source
Plain Language Summary	View source

ID	Term
D002289	Carcinoma, Non-Small-Cell Lung
C565324	Parkinson Disease 4, Autosomal Dominant Lewy Body

ID	Term
D002283	Carcinoma, Bronchogenic
D001984	Bronchial Neoplasms
D008175	Lung Neoplasms
D012142	Respiratory Tract Neoplasms
D013899	Thoracic Neoplasms
D009371	Neoplasms by Site
D009369	Neoplasms
D008171	Lung Diseases
D012140	Respiratory Tract Diseases

ID	Term
C582435	pembrolizumab
D016190	Carboplatin
D017239	Paclitaxel
D000068196	Albumin-Bound Paclitaxel
D000068437	Pemetrexed
C000710748	patritumab deruxtecan

ID	Term
D056831	Coordination Complexes
D009930	Organic Chemicals
D043823	Taxoids
D043822	Cyclodecanes
D003516	Cycloparaffins
D006840	Hydrocarbons, Alicyclic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D004224	Diterpenes
D013729	Terpenes
D000418	Albumins
D011506	Proteins
D000602	Amino Acids, Peptides, and Proteins
D006147	Guanine
D007042	Hypoxanthines
D011688	Purinones
D011687	Purines
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring
D006571	Heterocyclic Compounds
D005971	Glutamates
D024342	Amino Acids, Acidic
D000596	Amino Acids
D000600	Amino Acids, Dicarboxylic