Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Participants receive MK-7162 25 mg via oral tablets once daily (QD) throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 25 mg orally QD PLUS pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (every 3 weeks \[Q3W\]).

Participants receive MK-7162 50 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-71625 50 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W

Participants receive MK-7162 100 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 100 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W

Participants receive MK-7162 200 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 200 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W

MK-7162

Medical Director

The purposes of this study are to determine the safety and tolerability of MK-7162 when administered in combination with pembrolizumab (MK-3475) and to establish a preliminary recommended Phase 2 dose (RP2D) of MK-7162 when administered in combination with pembrolizumab.

Study of MK-7162 in Combination With Pembrolizumab (MK-3475) in Adult Participants With Advanced Solid Tumors (MK-7162-002)

Phase 1b Open-label Study of MK-7162 in Combination With Pembrolizumab (MK-3475) +/- Other Therapies in Participants With Advanced Solid Tumors

http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

The following events, if considered drug related by the investigator, are considered a DLT: Grade 4 nonhematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia; Grade 4 thrombocytopenia of any duration; Grade 3 thrombocytopenia associated with bleeding; Nonhematologic Adverse Events (AE) ≥Grade 3 with exceptions; Grade 3 or Grade 4 non-hematologic laboratory values if requires medical intervention, leads to hospitalization, persists for \>1 week, or results in a Drug-induced Liver Injury with exceptions; Grade 3 of 4 febrile neutropenia; Treatment-related toxicities that lead to discontinuation of study treatment during Cycles 1 or 2; Prolonged delay (\>2 weeks) in initiating Cycles 2 or 3 due to treatment-related toxicity; Missing \>25% of MK-7162 doses as a result of treatment-related AE during Cycles 1 or 2; Grade 5 toxicity.

An AE is defined as any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study treatment.

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. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention.

Blood samples were collected at designated time points for determining the AUC₀-₈ of MK-7162 in plasma when administered alone and in combination with pembrolizumab.

Blood samples were obtained at designated time points to determine the Cmin of MK-7162 in plasma.

Blood samples were collected at designated time points to determine the Cmax of MK-7162 in plasma when administered alone and in combination with pembrolizumab.

MK-7162 is a selective inhibitor of Indoleamine-2,3-dioxygenase-1 (IDO1) activity which, in turn, reduces the conversion of TRP to KYN. Venous blood samples were collected after an overnight fast for measurement of plasma levels of KYN as a pharmacodynamic biomarker of IDO1 inhibition.

MK-7162 is a selective inhibitor of Indoleamine-2,3-dioxygenase-1 (IDO1) activity which, in turn, reduces the conversion of TRP to KYN. Venous blood samples were collected at designated time points after an overnight fast for measurement of plasma levels of TRP as a pharmacodynamic biomarker of IDO1 inhibition.

ORR is defined as the percentage of participants in the analysis population who have a Complete Response (CR: Disappearance of all target lesions) or a Partial Response (PR: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters) per RECIST 1.1 as assessed by the Investigator. The percentage of participants who experience a CR or PR based on RECIST 1.1 will be presented.

Participants with PD by RECIST 1.1 as determined by investigator underwent confirmatory imaging to classify the disease as confirmed progressive disease (iCPD), unconfirmed progressive disease \[iUPD\]), stable disease (iSD), partial response (iPR) or complete response (iCR). iCPD definition: Worsening of target lesions (increase in the sum of diameters of ≥5 mm); Any significant growth in non-target lesions, Appearance of new lesions, increase in new lesion sum of diameters by ≥5 mm; Visible growth of new non-target lesions; or appearance of new factor that would have triggered PD by RECIST 1.1. Responses are classified as iSD or iPR (depending on the sum of diameters of the target lesions), or iCR if all lesions resolve. iUPD overall response is defined as none of the progression-confirming factors identified in iCPD occurs AND The target lesion sum of diameters (initial target lesions) remains above the initial PD threshold (by RECIST 1.1)

Merck Sharp & Dohme LLC

The safety analysis population includes all participants who received at least one dose of study treatment. Per protocol, disease progression of cancer under study was not considered an AE unless considered related to study treatment. Therefore, Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study treatment are excluded as AEs.

Participants receive MK-7162 25 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 25 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W

MK-7162 25mg + Pembro

Participants receive MK-7162 50 mg via oral tablets QD throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 50 mg orally QD PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle Q3W

MK-7162 50mg + Pembro

MK-7162 100mg + Pembro

MK-7162 200mg + Pembro

MK-7162 25 mg + Pembro

MK-7162 50 mg + Pembro

MK-7162 100 mg + Pembro

MK-7162 200 mg + Pembro

Total

Age, Continuous

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

Senior Vice President, Global Clinical Development

All participants who received at least one dose of study treatment and were observed for safety for 21 days after the first dose of assigned treatment or experienced a DLT prior to 21 days after the first dose of treatment.

Number of Participants Experiencing Dose-limiting Toxicities (DLTs) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 by the Investigator

All participants who received at least one dose of study treatment

Number of Participants Who Experienced an Adverse Event (AE)

Number of Participants Who Discontinued Study Drug Due to an AE

Day 1, Cycle 1: MK-7162 alone

Day 15, Cycle 1: MK-7162 alone

Day 1, Cycle 3: MK-7162 + Pembrolizumab

All participants who were compliant with the study procedures and have available data from at least one treatment.

Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab

All participants who were compliant with the study procedures and have available plasma data.

Minimum Plasma Concentration (Cmin) of MK-7162

Day 1 Cycle 1: MK-7162 alone

Day15 Cycle 1: MK-7162 Alone

Day 1 Cycle 3: MK-7162+ Pembrolizumab

Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab

Cycle 1 Day 1, Predose

Cycle 1 Day 1, 1 Hour (hr) Postdose

Cycle 1 Day 1, 2 Hr Postdose

Cycle 1 Day 1, 4 Hr Postdose

Cycle 1 Day1, 8 Hr Postdose

Cycle 1 Day 15, Predose

Cycle 1 Day 15, 1 Hr Postdose

Cycle 1 Day 15, 2 Hr Postdose

Cycle 1 Day 15, 4 Hr Postdose

Cycle 1 Day 15, 8 Hr Postdose

Cycle 2 Day 1, Predose

Cycle 3 Day 1, Predose

Cycle 3 Day 1, 1 Hr Postdose

Cycle 3 Day 1, 2 Hr Postdose

Cycle 3 Day 1, 4 Hr Postdose

Cycle 3 Day 1, 8 Hr Postdose

Cycle 3 Day 15, PreDose

All participants who were compliant with the study procedures and have available data from at least one treatment

Kynurenine (KYN) Biomarker Plasma Concentration

Cycle 1 Day1, Predose

Cycle 1 Day 1, 1 Hr Postdose

Cycle 1 Day 1, 8 Hr Postdose

Cycle 1 Day 15,8 Hr Postdose

Cyle 3 Day 1, 8 Hr Postdose

Cycle 3 Day 15, Predose

Tryptophan (TRP) Biomarker Plasma Concentration

All participants with a baseline scan that demonstrated measurable disease by the investigator's assessment, and who were administered at least one dose of study treatment

Objective Response Rate (ORR) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator

iUPD

iCPD

All participants who had follow up tumor imaging subsequent to initial progressive disease per RECIST 1.1 by investigator assessment

Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors

Cycle 1: Participants receive MK-7162 25 mg via oral tablets once daily (QD) throughout the 3-week cycle. Cycles 2 through 36: Participants receive MK-7162 25 mg orally QD PLUS pembrolizumab 200 mg via intravenous (IV) infusion on Day 1 of each 3-week cycle (every 3 weeks \[Q3W\]).

Spots Global Cancer Trial Database for Study of MK-7162 in Combination With Pembrolizumab (MK-3475) in Adult Participants With Advanced Solid Tumors (MK-7162-002)

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

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