Researchers want to learn if MK-1084, the study medicine, can treat advanced or metastatic non-squamous NSCLC. MK-1084 is a targeted therapy, which is a treatment that works to control how specific types of cancer cells grow and spread. The goals of this study are to learn: * About the safety of MK-1084 and if people tolerate it when taken with other treatments * How many people have the cancer respond (get smaller or go away) to the treatments
This is a substudy of the master protocol MK-3475-U01 (KEYMAKER-U01) - NCT04165798. Per amendment 3, the MK-1084 + Cetuximab arm was discontinued.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
140
Oral administration
IV infusion
IV Infusion
Number of Participants Who Experience a Dose Limiting Toxicity (DLT)
DLT will be defined as any drug-related AE observed during the DLT evaluation period (up to 42 days) that results in a change to a given dose or a delay in initiating the next treatment.
Time frame: Up to 42 days
Number of Participants Who Experience an Adverse Event (AE)
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that experience AEs will be reported.
Time frame: Up to approximately 63 months
Number of Participants Who Discontinue Study Treatment Due to an AE
An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. The number of participants that discontinue study intervention due to an AE will be reported.
Time frame: Up to approximately 62 months
Objective Response Rate (ORR)
ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
Time frame: Up to approximately 63 months
Duration of Response (DOR)
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per RECIST 1.1, DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 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 at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by BICR will be presented.
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IV Infusion
Participants receive rescue medication at the investigator's discretion for prevention of nausea and vomiting, per approved product label. Recommended rescue medications are histamine-1 (H1) receptor antagonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, or steroid mouthwash (dexamethasone or equivalent), 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, neurokinin 1 (NK-1) receptor antagonist and corticosteroid.
Clermont Oncology Center ( Site 0041)
Clermont, Florida, United States
RECRUITINGUniversity of Illinois Hospital & Health Sciences System ( Site 0044)
Chicago, Illinois, United States
RECRUITINGProvidence Portland Medical Center ( Site 0043)
Portland, Oregon, United States
RECRUITINGProvidence Oncology and Hematology Care Clinic - Westside ( Site 0059)
Portland, Oregon, United States
RECRUITINGHospital São Lucas da PUCRS ( Site 0283)
Porto Alegre, Rio Grande do Sul, Brazil
RECRUITINGFundação Pio XII - Hospital de Câncer de Barretos ( Site 0282)
Barretos, São Paulo, Brazil
RECRUITINGFundação Faculdade Regional de Medicina de São José do Rio Preto ( Site 0286)
São José do Rio Preto, São Paulo, Brazil
RECRUITINGHospital Paulistano ( Site 0280)
São Paulo, São Paulo, Brazil
RECRUITINGCentro de Estudios Clínicos SAGA-CECSAGA ( Site 0162)
Santiago, Region M. de Santiago, Chile
RECRUITINGFALP ( Site 0161)
Santiago, Region M. de Santiago, Chile
RECRUITING...and 18 more locations
Time frame: Up to approximately 63 months
Progression-Free Survival (PFS)
PFS is defined as the time from randomization to the first documented PD or death due to any cause, whichever occurs first as assessed by 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 as assessed by BICR will be presented.
Time frame: Up to approximately 71 months
Area Under the Curve From Time 0 to the End of the Dosing Interval (AUC tau)
Blood samples will be collected at multiple time points to estimate AUC tau.
Time frame: Predose and at designated time points post-dose (up to approximately 63 months)
Maximum Plasma Concentration (Cmax)
Blood samples will be collected at multiple time points to estimate Cmax.
Time frame: Predose and at designated time points post-dose (up to approximately 63 months)
Minimum Observed Concentration (Ctrough)
Blood samples will be collected at multiple time points to estimate Ctrough.
Time frame: Predose and at designated time points post-dose (up to approximately 63 months)