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MK-2870 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (MK-2870-008)

Primary Purpose

Non-small Cell Lung Cancer, Solid Tumors, Programmed Cell Death-1 (PD1, PD-1)

Status
Not yet recruiting
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
MK-2870
Pembrolizumab
Carboplatin
Sponsored by
Merck Sharp & Dohme LLC
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: Arm 1: Histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, or been intolerant to, all treatment known to confer clinical benefit. Arms 2 and 3: Have a histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC (Stage IIIB or IIIC disease and not candidates for surgical resection or definitive chemoradiation, or Stage IV NSCLC, AJCC Staging Manual, version 8). Arms 2 and 3: Confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy Arm 3: Has tumor tissue that demonstrates PD-L1 TPS ≥ 50% as determined by PD-L1 IHC 22C3 pharmDx assay by local laboratory If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (100 days for MK-2870 and 90 days for carboplatin [no restriction for pembrolizumab]) AND agrees to refrain from donating sperm AND is either abstinent and agrees to remain abstinent or uses highly effective contraception For females (assigned at birth), is not pregnant or breastfeeding and ≥1 of the following applies: is not a participant of childbearing potential (POCBP) OR is a POCBP and uses highly effective contraction Arm 1: Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline Measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology Archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated has been provided Have a life expectancy of at least 3 months Have an ECOG performance status of 0 or 1 within 3 days before the start of study intervention Exclusion Criteria: Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible Has Grade ≥2 peripheral neuropathy Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease 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 >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention Received prior treatment with a TROP2-targeted ADC Received prior treatment with a topoisomerase I-containing ADC Arm 1: Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis Arms 2 and 3: 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) Arms 2 and 3: Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their advanced or metastatic NSCLC Arms 2 and 3: Has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study intervention Received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention Requires treatment with a strong inhibitor or inducer of CYP3A4 at least 14 days before the first dose of study intervention and throughout the study Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration Arms 2 and 3: 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 the first dose of study medication Arms 2 and 3: Active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) Known additional malignancy that is progressing or has required active treatment within the past 3 years Known active CNS metastases and/or carcinomatous meningitis History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease Active infection requiring systemic therapy History of HIV infection Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator Known psychiatric or substance abuse disorder A severe hypersensitivity reaction to treatment a monoclonal antibody/component of the study intervention

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Experimental

    Experimental

    Arm Label

    Arm 1: MK-2870 Monotherapy

    Arm 2: MK-2870 + Pembrolizumab Combination Therapy

    Arm 3: MK-2870 + Pembrolizumab/Carboplatin Combination Therapy

    Arm Description

    Participants receive single doses of MK-2870 monotherapy Q2W.

    Participants receive MK-2870 Q2W in combination with pembrolizumab Q6W.

    Participants receive MK-2870 Q2W in combination with pembrolizumab Q6W and carboplatin Q3W.

    Outcomes

    Primary Outcome Measures

    Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
    A DLT is defined as any of the following: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia or lymphopenia; any nonhematologic AE ≥Grade 3 in severity (with some exceptions); any Grade 3 or Grade 4 nonhematologic laboratory value (if certain criteria are met); febrile neutropenia Grade 3 or Grade 4; a prolonged delay (>2 weeks) in initiating MK-2870 second dose due to intervention-related toxicity; any intervention-related toxicity that causes the participant to discontinue intervention during DLT evaluation period; or any Grade 5 toxicity. All toxicities will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
    Number of Participants Experiencing ≥1 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.
    Number of Participants Discontinuing from Study Therapy due to 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.

    Secondary Outcome Measures

    Area Under the Plasma Concentration-Time Curve (AUC) of MK-2870-Antibody-Drug Conjugate (MK-2870-ADC)
    The AUC of MK-2870-ADC will be determined in participants from Arm 1.
    Maximum Plasma Concentration (Cmax) of MK-2870-ADC
    The Cmax of MK-2870-ADC will be determined in participants from Arm 1.
    Minimum Plasma Concentration (Cmin) of MK-2870-ADC
    The Cmin of MK-2870-ADC will be determined in participants from Arm 1.
    Apparent terminal half-life (t½) of MK-2870-ADC
    The t½ of MK-2870-ADC will be determined in participants from Arm 1.
    Time to Maximum Plasma Concentration (Tmax) of MK-2870-ADC
    The Tmax of MK-2870-ADC will be determined in participants from Arm 1.
    Clearance (CL) of MK-2870-ADC
    The CL of MK-2870-ADC will be determined in participants from Arm 1.
    Volume of Distribution (Vz) of MK-2870-ADC
    The Vz of MK-2870-ADC will be determined in participants from Arm 1.
    Accumulation Ratio (Rac) of MK-2870-ADC
    The Rac of MK-2870-ADC will be determined in participants from Arm 1.
    Area Under the Plasma AUC of MK-2870-Total Antibody (MK-2870-TAB)
    The AUC of MK-2870-TAB will be determined in participants from Arm 1.
    Cmax of MK-2870-TAB
    The Cmax of MK-2870-TAB will be determined in participants from Arm 1.
    Cmin of MK-2870-TAB
    The Cmin of MK-2870-TAB will be determined in participants from Arm 1.
    t½ of MK-2870-TAB
    The t½ of MK-2870-TAB will be determined in participants from Arm 1.
    Tmax of MK-2870-TAB
    The Tmax of MK-2870-TAB will be determined in participants from Arm 1.
    CL of MK-2870-TAB
    The CL of MK-2870-TAB will be determined in participants from Arm 1.
    Vz of MK-2870-TAB
    The Vz of MK-2870-TAB will be determined in participants from Arm 1.
    Rac of MK-2870-TAB
    The Rac of MK-2870-TAB will be determined in participants from Arm 1.
    Cmax of MK-2870-ADC Coadministered with Pembrolizumab
    The Cmax of MK-2870-ADC when coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Cmin of MK-2870-ADC Coadministered with Pembrolizumab
    The Cmin of MK-2870-ADC when coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Rac of MK-2870-ADC Coadministered with Pembrolizumab
    The Rac of MK-2870-ADC when coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Cmax of MK-2870-TAB Coadministered with Pembrolizumab
    The Cmax of MK-2870-TAB when coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Cmin of MK-2870-TAB Coadministered with Pembrolizumab
    The Cmin of MK-2870-TAB when coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Rac of MK-2870-TAB Coadministered with Pembrolizumab
    The Rac of MK-2870-TAB when coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Cmax of KL610023 Coadministered with Pembrolizumab
    The Cmax of KL610023 (free payload) when MK-2870 is coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Rac of KL610023 Coadministered with Pembrolizumab
    The Rac of KL610023 (free payload) when MK-2870 is coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    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 (RECIST1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
    Duration of Response (DOR)
    DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause.
    Incidence of Antidrug Antibodies (ADA) to MK-2870
    The incidence of ADA will be determined in participants from Arms 2 and 3.

    Full Information

    First Posted
    September 15, 2023
    Last Updated
    October 13, 2023
    Sponsor
    Merck Sharp & Dohme LLC
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    1. Study Identification

    Unique Protocol Identification Number
    NCT06049212
    Brief Title
    MK-2870 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (MK-2870-008)
    Official Title
    Phase 1 Trial of MK-2870 as Monotherapy and in Combination With Pembrolizumab ± Chemotherapy in Subjects With Advanced Solid Tumors
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    October 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    October 27, 2023 (Anticipated)
    Primary Completion Date
    June 6, 2025 (Anticipated)
    Study Completion Date
    June 6, 2025 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Merck Sharp & Dohme LLC

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This is a phase 1 trial of the safety, tolerability, and pharmacokinetics (PK) of MK-2870 monotherapy, and of MK-2870 in combination with pembrolizumab (MK-3475) or pembrolizumab + carboplatin, in Japanese participants with advanced solid tumors or treatment-naïve advanced or metastatic non-small cell lung cancer (NSCLC).

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Non-small Cell Lung Cancer, Solid Tumors, Programmed Cell Death-1 (PD1, PD-1), Programmed Cell Death 1 Ligand 1(PDL1, PD-L1), Programmed Cell Death 1 Ligand 2 (PDL2, PD-L2)

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 1
    Interventional Study Model
    Sequential Assignment
    Masking
    None (Open Label)
    Allocation
    Non-Randomized
    Enrollment
    48 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm 1: MK-2870 Monotherapy
    Arm Type
    Experimental
    Arm Description
    Participants receive single doses of MK-2870 monotherapy Q2W.
    Arm Title
    Arm 2: MK-2870 + Pembrolizumab Combination Therapy
    Arm Type
    Experimental
    Arm Description
    Participants receive MK-2870 Q2W in combination with pembrolizumab Q6W.
    Arm Title
    Arm 3: MK-2870 + Pembrolizumab/Carboplatin Combination Therapy
    Arm Type
    Experimental
    Arm Description
    Participants receive MK-2870 Q2W in combination with pembrolizumab Q6W and carboplatin Q3W.
    Intervention Type
    Biological
    Intervention Name(s)
    MK-2870
    Other Intervention Name(s)
    SKB264
    Intervention Description
    MK-2870 injection powder for intravenous (IV) infusion.
    Intervention Type
    Biological
    Intervention Name(s)
    Pembrolizumab
    Other Intervention Name(s)
    MK-3475
    Intervention Description
    Pembrolizumab solution for IV infusion.
    Intervention Type
    Drug
    Intervention Name(s)
    Carboplatin
    Intervention Description
    Carboplatin solution for IV infusion.
    Primary Outcome Measure Information:
    Title
    Number of Participants Experiencing Dose-Limiting Toxicity (DLT)
    Description
    A DLT is defined as any of the following: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia or lymphopenia; any nonhematologic AE ≥Grade 3 in severity (with some exceptions); any Grade 3 or Grade 4 nonhematologic laboratory value (if certain criteria are met); febrile neutropenia Grade 3 or Grade 4; a prolonged delay (>2 weeks) in initiating MK-2870 second dose due to intervention-related toxicity; any intervention-related toxicity that causes the participant to discontinue intervention during DLT evaluation period; or any Grade 5 toxicity. All toxicities will be graded using National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) v5.0.
    Time Frame
    Up to 21 days after each dose
    Title
    Number of Participants Experiencing ≥1 Adverse Event (AE)
    Description
    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.
    Time Frame
    Up to ~36 months
    Title
    Number of Participants Discontinuing from Study Therapy due to AE
    Description
    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.
    Time Frame
    Up to ~36 months
    Secondary Outcome Measure Information:
    Title
    Area Under the Plasma Concentration-Time Curve (AUC) of MK-2870-Antibody-Drug Conjugate (MK-2870-ADC)
    Description
    The AUC of MK-2870-ADC will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Maximum Plasma Concentration (Cmax) of MK-2870-ADC
    Description
    The Cmax of MK-2870-ADC will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Minimum Plasma Concentration (Cmin) of MK-2870-ADC
    Description
    The Cmin of MK-2870-ADC will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Apparent terminal half-life (t½) of MK-2870-ADC
    Description
    The t½ of MK-2870-ADC will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Time to Maximum Plasma Concentration (Tmax) of MK-2870-ADC
    Description
    The Tmax of MK-2870-ADC will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Clearance (CL) of MK-2870-ADC
    Description
    The CL of MK-2870-ADC will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Volume of Distribution (Vz) of MK-2870-ADC
    Description
    The Vz of MK-2870-ADC will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Accumulation Ratio (Rac) of MK-2870-ADC
    Description
    The Rac of MK-2870-ADC will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Area Under the Plasma AUC of MK-2870-Total Antibody (MK-2870-TAB)
    Description
    The AUC of MK-2870-TAB will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Cmax of MK-2870-TAB
    Description
    The Cmax of MK-2870-TAB will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Cmin of MK-2870-TAB
    Description
    The Cmin of MK-2870-TAB will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    t½ of MK-2870-TAB
    Description
    The t½ of MK-2870-TAB will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Tmax of MK-2870-TAB
    Description
    The Tmax of MK-2870-TAB will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    CL of MK-2870-TAB
    Description
    The CL of MK-2870-TAB will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Vz of MK-2870-TAB
    Description
    The Vz of MK-2870-TAB will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Rac of MK-2870-TAB
    Description
    The Rac of MK-2870-TAB will be determined in participants from Arm 1.
    Time Frame
    Day 1: Preinfusion and 0.5, 2, 4, 8, 24, 48, and 72 hours postinfusion
    Title
    Cmax of MK-2870-ADC Coadministered with Pembrolizumab
    Description
    The Cmax of MK-2870-ADC when coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Time Frame
    Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
    Title
    Cmin of MK-2870-ADC Coadministered with Pembrolizumab
    Description
    The Cmin of MK-2870-ADC when coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Time Frame
    Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
    Title
    Rac of MK-2870-ADC Coadministered with Pembrolizumab
    Description
    The Rac of MK-2870-ADC when coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Time Frame
    Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
    Title
    Cmax of MK-2870-TAB Coadministered with Pembrolizumab
    Description
    The Cmax of MK-2870-TAB when coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Time Frame
    Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
    Title
    Cmin of MK-2870-TAB Coadministered with Pembrolizumab
    Description
    The Cmin of MK-2870-TAB when coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Time Frame
    Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
    Title
    Rac of MK-2870-TAB Coadministered with Pembrolizumab
    Description
    The Rac of MK-2870-TAB when coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Time Frame
    Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
    Title
    Cmax of KL610023 Coadministered with Pembrolizumab
    Description
    The Cmax of KL610023 (free payload) when MK-2870 is coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Time Frame
    Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
    Title
    Rac of KL610023 Coadministered with Pembrolizumab
    Description
    The Rac of KL610023 (free payload) when MK-2870 is coadministered with pembrolizumab will be determined in participants from Arms 2 and 3.
    Time Frame
    Cycle 1 and 2: Days 1 and 29 preinfusion and 0.5 hours postinfusion (each cycle is 29 days)
    Title
    Objective Response Rate (ORR)
    Description
    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 (RECIST1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented.
    Time Frame
    Up to ~36 months
    Title
    Duration of Response (DOR)
    Description
    DOR is defined as the time from first documented evidence of CR or PR until disease progression or death due to any cause.
    Time Frame
    Up to ~36 months
    Title
    Incidence of Antidrug Antibodies (ADA) to MK-2870
    Description
    The incidence of ADA will be determined in participants from Arms 2 and 3.
    Time Frame
    Up to ~36 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Arm 1: Histologically or cytologically confirmed advanced/metastatic solid tumor by pathology report and have received, or been intolerant to, all treatment known to confer clinical benefit. Arms 2 and 3: Have a histologically or cytologically confirmed diagnosis of advanced or metastatic NSCLC (Stage IIIB or IIIC disease and not candidates for surgical resection or definitive chemoradiation, or Stage IV NSCLC, AJCC Staging Manual, version 8). Arms 2 and 3: Confirmation that EGFR-, ALK-, or ROS1-directed therapy is not indicated as primary therapy Arm 3: Has tumor tissue that demonstrates PD-L1 TPS ≥ 50% as determined by PD-L1 IHC 22C3 pharmDx assay by local laboratory If capable of producing sperm, the participant agrees to the following during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention (100 days for MK-2870 and 90 days for carboplatin [no restriction for pembrolizumab]) AND agrees to refrain from donating sperm AND is either abstinent and agrees to remain abstinent or uses highly effective contraception For females (assigned at birth), is not pregnant or breastfeeding and ≥1 of the following applies: is not a participant of childbearing potential (POCBP) OR is a POCBP and uses highly effective contraction Arm 1: Participants who have AEs due to previous anticancer therapies must have recovered to ≤Grade 1 or baseline Measurable disease by RECIST 1.1 as assessed by the local site investigator/radiology Archival tumor tissue sample or newly obtained core or incisional biopsy of a tumor lesion not previously irradiated has been provided Have a life expectancy of at least 3 months Have an ECOG performance status of 0 or 1 within 3 days before the start of study intervention Exclusion Criteria: Has symptomatic ascites or pleural effusion. A participant who is clinically stable following treatment for these conditions (including therapeutic thoraco- or paracentesis) is eligible Has Grade ≥2 peripheral neuropathy Has history of documented severe dry eye syndrome, severe Meibomian gland disease and/or blepharitis, or corneal disease that prevents/delays corneal healing Has active inflammatory bowel disease requiring immunosuppressive medication or previous clear history of inflammatory bowel disease 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 >480 ms, and/or other serious cardiovascular and cerebrovascular diseases within the 6 months preceding study intervention Received prior treatment with a TROP2-targeted ADC Received prior treatment with a topoisomerase I-containing ADC Arm 1: Has received any prior immunotherapy and was discontinued from that treatment due to a Grade 3 or higher irAE (except endocrine disorders that can be treated with replacement therapy) or was discontinued from that treatment due to Grade 2 myocarditis or recurrent Grade 2 pneumonitis Arms 2 and 3: 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) Arms 2 and 3: Has received prior systemic chemotherapy or other targeted or biological antineoplastic therapy for their advanced or metastatic NSCLC Arms 2 and 3: Has received radiation therapy to the lung that is >30 Gy within 6 months of the first dose of study intervention Received prior systemic anticancer therapy including investigational agents within 4 weeks before allocation Received prior radiotherapy within 2 weeks of start of study intervention, or radiation-related toxicities, requiring corticosteroids Received a live or live-attenuated vaccine within 30 days before the first dose of study intervention Requires treatment with a strong inhibitor or inducer of CYP3A4 at least 14 days before the first dose of study intervention and throughout the study Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration Arms 2 and 3: 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 the first dose of study medication Arms 2 and 3: Active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid) Known additional malignancy that is progressing or has required active treatment within the past 3 years Known active CNS metastases and/or carcinomatous meningitis History of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease Active infection requiring systemic therapy History of HIV infection Concurrent active Hepatitis B (defined as HBsAg positive and/or detectable HBV DNA) and Hepatitis C virus (defined as anti-HCV Ab positive and detectable HCV RNA) infection History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might confound the results of the study or interfere with the participant's participation for the full duration of the study, such that it is not in the best interest of the participant to participate, in the opinion of the treating investigator Known psychiatric or substance abuse disorder A severe hypersensitivity reaction to treatment a monoclonal antibody/component of the study intervention
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Medical Director
    Organizational Affiliation
    Merck Sharp & Dohme LLC
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
    IPD Sharing URL
    http://engagezone.msd.com/ds_documentation.php
    Links:
    URL
    http://www.merckclinicaltrials.com
    Description
    Merck Clinical Trials Information

    Learn more about this trial

    MK-2870 as Monotherapy and in Combination With Pembrolizumab in Participants With Advanced Solid Tumors (MK-2870-008)

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