None listed
Conditions
Interventions
Tests products: MK-1084: Tablet of 25 mg, 50 mg. It will be administered in a dose of 100 mg by oral route once daily. It will be administered before MK-3475A. MK-3475A: Solution of 165 mg/mL. It will
Sponsors
Merck Sharp & Dohme LLC., (una subsidiaria de Merck & Co. Inc.)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Assigned Female Sex at Birth A participant assigned female sex at birth is eligible to participate if not breastfeeding during the study intervention period and for at least 10 days after the last dose of study intervention (MK-1084), 120 days after MK-3475A, and 180 days after chemotherapy. Type of Participant and Disease Characteristics Nonsquamous NSCLC (Stage IIIB, Stage IIIC) not eligible for curative resection or chemoradiation as determined by a multidisciplinary tumor board and/or radiation oncologist, surgeon and medical oncologist or Stage IV: M1a, M1b, or M1c, (AJCC Staging Manual, Version 9). Note: Mixed tumors will be characterized by the predominant cell type; if small cell elements are present, the participant is ineligible. Measurable (eligible for selection as target lesions) disease based on RECIST 1.1, as determined by the local site investigator/radiology assessment. Lesions that appear measurable, but are situated in a previously irradiated area, can be considered measurable if they have shown documented growth since the completion of radiation. Provides an archival tumor tissue sample (=5 years) or newly obtained core, incisional, excisional biopsy of a tumor lesion not previously irradiated to enable central laboratory testing of KRAS G12C status, PD-L1 status, and biomarker research. Note: Required at screening prior to randomization. If a participant is enrolled based on local KRAS G12C or PD-L1 testing results, tissue for central laboratory testing will still be required. PD-L1 statuses (TPS 18 years of age. Assigned Male Sex at Birth If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate the study intervention after the last dose of study intervention. The length of time required to continue contraception for the study intervention is: - MK-1084: 10 days - MK-3475A: no male contraception measures are required - Chemotherapy: 90 days • Refrains from donating sperm •Uses a penile/external condom when having penile-vaginal intercourse with a nonparticipant of childbearing potential who is not currently pregnant PLUS partner use of an additional contraceptive method (refer to Section 10.5.3), as a condom may break or leak. Contraceptive use should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions are more stringent than the requirements above, the l
Exclusion criteria
Exclusion criteria: Medical Conditions Diagnosis of small cell lung cancer or, for mixed tumors, presence of small cell elements. Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease (eg, Crohn’s disease, ulcerative colitis, or chronic diarrhea). Has uncontrolled, significant cardiovascular disease or cerebrovascular disease including New York Heart Association Class III or IV congestive heart failure, unstable angina, myocardial infarction, uncontrolled symptomatic arrhythmia, prolongation of QTcF interval to >470 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention. Is unable to swallow orally administered medication or has a gastrointestinal disorder affecting absorption. HIV-infected participants with a history of Kaposi’s sarcoma and/or Multicentric Castleman’s Disease. Prior/Concomitant Therapy Received prior systemic anticancer therapy for their advanced or metastatic NSCLC. Note: Prior treatment with chemotherapy and/or radiation as part of neoadjuvant or adjuvant therapy or chemoradiation therapy for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of advanced or metastatic NSCLC. Received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent, or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137). Note: Prior treatment with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent for nonmetastatic NSCLC is allowed as long as therapy was completed at least 12 months before diagnosis of advanced or metastatic NSCLC. Has received previous treatment with an agent targeting KRAS. Is unable to adhere to the prohibited medications and washout times as per Section 6.5. Received radiation therapy to the lung that is >30 Gray within 6 months of start of study intervention. Received prior radiotherapy within 2 weeks of start of study intervention, or has radiation-related toxicities, requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last palliative radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention. Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed. Prior/Concurrent Clinical Study Experience Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration. Diagnostic Assessments 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 prior to the first dose of study intervention. Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Participants with low-risk earlystage prostate cancer (T1-T2a, Gleason score =6, and PSA <10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded. Known active CNS metastases and/or carcinomatous meningitis. Participants
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Testing: stratified log-rank test Estimation: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Progression-Free Survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first documented disease progression per RECIST 1.1 by blinded independent central review (BICR) or death due to any cause, whichever occurs first. | — |
Secondary
| Measure | Time frame |
|---|---|
| Testing: stratified log-rank test Estimation: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Progression-Free Survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first documented disease progression per RECIST 1.1 by blinded independent central review (BICR) or death due to any cause, whichever occurs first.;Testing: stratified log-rank test Estimation: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Progression-Free Survival (PFS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to the first documented disease progression per RECIST 1.1 by blinded independent central review (BICR) or death due to any cause, whichever occurs first.;Testing: stratified log-rank test Estimation: Stratified Cox model with Efron’s tie handling method NAME OF THE RESULT: Overall Survival (OS) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From randomization to death due to any cause.;Confirmed complete response (CR) or partial response (PR) per RECIST 1.1 as assessed by BICR. Testing and Estimation: stratified Miettinen and Nurminen’s method with strata weighting by sample size. NAME OF THE RESULT: Objective Response (OR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: Before either initiation of any new anti-cancer therapy or death.;Estimation: Kaplan-Meier medians and quartiles (if sample size permits). NAME OF THE RESULT: Duration of Response (DOR) PERIOD OF TIME WHERE TE MEASUREMENT WILL BE CONDUCTED AND WHICH WILL ALLOW OBTAINING THE PRIMARY RESULT: From the first documented evidence of CR or PR by BICR until disease progression or death due to any cause, whichever occurs first.;Clinical review of adverse events and other relevant parameters, including | — |
Countries
Peru
Contacts
Public ContactNELVA GARCIA
MERCK SHARP & DOHME PERU S.R.L.
Outcome results
None listed