Lung Neoplasm Malignant
Conditions
Brief summary
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
Detailed description
This is a substudy of the master protocol MK-3475-U01 (KEYMAKER-U01) - NCT04165798.
Interventions
DRUGMK-1084
Oral administration
BIOLOGICALPatritumab deruxtecan
IV infusion
BIOLOGICALSacituzumab tirumotecan
IV Infusion
BIOLOGICALCetuximab
IV Infusion
Participants receive rescue medication at the investigator's discretion, per approved product label. Recommended rescue medications are histamine -1 (H1) receptor agonist, histamine-2 (H2) receptor antagonist, acetaminophen or equivalent, dexamethasone or equivalent infusion, or steroid mouthwash (dexamethasone or equivalent) for prevention of chemotherapy induced nausea and vomiting.
Sponsors
Merck Sharp & Dohme LLC
Daiichi Sankyo
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Participants will be enrolled and treated sequentially during dose escalation followed by parallel assignment in the expansion phase.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * Has histologically or cytologically confirmed diagnosis of advanced or metastatic non-squamous non-small cell lung cancer (NSCLC) * Has tumor tissue or circulating tumor deoxyribonucleic acid (ctDNA) that demonstrates the presence of Kirsten rat sarcoma viral oncogene (KRAS) mutation of glycine to cysteine at codon 12 (G12C) mutations * Has documented disease progression after receiving 1-2 prior lines of programmed cell death protein 1 (PD-1)/programmed death-ligand 1 (PD-L1) therapy and platinum-based chemotherapy * Provides archival tumor tissue sample of a tumor lesion not previously irradiated * Has provided tissue prior to treatment allocation/randomization from a newly obtained biopsy of a tumor lesion not previously irradiated * Participants with human immunodeficiency virus (HIV) infection must have well-controlled HIV on antiretroviral therapy (ART) per protocol
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experience a Dose Limiting Toxicity (DLT) | Up to 42 days | 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. |
| Number of Participants Who Experience an Adverse Event (AE) | Up to approximately 65 months | 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. |
| Number of Participants Who Discontinue Study Treatment Due to an AE | Up to approximately 64 months | 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. |
| Objective Response Rate (ORR) | Up to approximately 65 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of Response (DOR) | Up to approximately 65 months | 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. |
| Progression-Free Survival (PFS) | Up to approximately 124 months | 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. |
| Area Under the Curve From Time 0 to the End of the Dosing Interval (AUC tau) | Predose and at designated time points post-dose (up to approximately 65 months) | Blood samples will be collected at multiple time points to estimate AUC tau. |
| Maximum Plasma Concentration (Cmax) | Predose and at designated time points post-dose (up to approximately 65 months) | Blood samples will be collected at multiple time points to estimate Cmax. |
| Minimum Observed Concentration (Ctrough) | Predose and at designated time points post-dose (up to approximately 65 months) | Blood samples will be collected at multiple time points to estimate Ctrough. |
Countries
Israel, South Korea, United States
Contacts
CONTACTToll Free Toll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed