Solid Neoplasms
Conditions
Brief summary
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.
Interventions
DRUGMK-7162
oral tablets
BIOLOGICALPembrolizumab
IV infusion
Sponsors
Merck Sharp & Dohme LLC
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Has a histologically- or cytologically-confirmed advanced/metastatic solid tumor by pathology report and have received, or been intolerant to, or been ineligible for all treatment known to confer clinical benefit. Participants with solid tumors of any type are eligible for enrollment. * Has stage III or stage IV disease that is not surgically resectable. * Has measurable disease by RECIST 1.1 criteria as assessed by the local site investigator/radiology. * Has 1 or more discrete malignant lesions that are amenable to ≥2 separate biopsies guided by one of the following modalities: visual inspection, ultrasound guidance, or cross sectional image guidance (computed tomography/magnetic resonance imaging \[CT/MRI\]). * Has an evaluable baseline tumor sample to submit for analysis. * Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG) Performance Scale. * Demonstrates adequate organ function. * If male, must agree to use contraception and refrain from donating sperm during the treatment period and for ≥120 days after last dose of study treatment. * If female, is not pregnant or breastfeeding, and if a woman of childbearing potential (WOCCBP), agrees to use contraception during the treatment period and for ≥120 days after last dose of study treatment.
Exclusion criteria
* Has a history of a second malignancy, unless potentially curative treatment has been completed with no evidence of malignancy for 2 years. (Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, superficial bladder cancer, in situ cervical cancer, or other in-situ cancers.) * Has a known active central nervous system metastasis and/or carcinomatous meningitis. * Has had a severe hypersensitivity reaction to treatment with a monoclonal antibody/components of the study treatment(s). * Has an active autoimmune disease that has required systemic treatment in the past 2 years except vitiligo or resolved childhood asthma/atopy. * Has a history of vasculitis. * Has an active infection requiring systemic therapy. * Has symptomatic ascites or pleural effusion. * Has interstitial lung disease that has required oral or intravenous glucocorticoids to assist with management. * Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis. * Has undergone prior allogeneic hematopoietic stem cell transplantation within the last 5 years. (Note: Participants who have had a stem cell transplant \>5 years ago are eligible as long as there are no symptoms of graft-versus-host disease \[GVHD\].) * Has a known history of human immunodeficiency virus (HIV) infection. * Has known active Hepatitis B or known active Hepatitis C virus infection. * Is pregnant or breastfeeding, or expecting to conceive or father children within the projected duration of the study. * Has not fully recovered from any effects of major surgery without significant detectable infection. * Has received prior systemic anti-cancer therapy including investigational agents or has used an investigational device within 28 days prior to the first dose of study treatment. (Notes: Participants must have recovered from all AEs due to previous therapies to ≤Grade 1 or baseline. Prior exposure to immunotherapeutics is allowed, including programmed cell death-1 (PD-1) and programmed cell death-ligand 1 (PD-L1) inhibitors, provided the participant did not experience ≥Grade 3 drug-related toxicity on monotherapy with a PD-1 or PD-L1 inhibitor. * Has been previously treated with an Indoleamine-2,3-dioxygenase-1 (IDO1) inhibitor (e.g., epacadostat, BMS-986205) * Has received prior radiotherapy within 2 weeks of start of study treatment. * Is receiving a monoamine oxidase inhibitor (MAOI) or any drug which has significant MAOI activity (e.g., meperidine, linezolid, methylene blue) within the 21 days before screening, or has a history of Serotonin Syndrome after receiving serotonergic drugs. * Is expected to require any non-protocol antineoplastic therapy while on study. * Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy in excess of replacement doses (the equivalent of prednisone ≤10 mg/day is acceptable), or on any other form of immunosuppressive medication. * Has received a live-virus vaccine within 30 days prior to first dose of study medication.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Experiencing Dose-limiting Toxicities (DLTs) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 by the Investigator | Cycle 1 and Cycle 2 (Up to 6 weeks) | 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. |
| Number of Participants Who Experienced an Adverse Event (AE) | Up to Approximately 27 Months | 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. |
| Number of Participants Who Discontinued Study Drug Due to an AE | Up to Approximately 26 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. 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Day 1: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose | 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. |
| Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Day 1: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose | 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. |
| Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Days 1 & 15; and Cycle 3, Day 1 | 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. |
| Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | Up to approximately 28 months | 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) |
| Objective Response Rate (ORR) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator | Up to approximately 28 months | 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. |
| Minimum Plasma Concentration (Cmin) of MK-7162 | Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Day 14 | Blood samples were obtained at designated time points to determine the Cmin of MK-7162 in plasma. |
| Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Days 1 and 15 and Cycle 3, Day 1 | 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. |
Countries
Canada, Israel, South Korea, United States
Participant flow
Recruitment details
This study included a screening period to determine eligibility. 41 participants were screened for this study and 33 were randomized.
Participants by arm
| Arm | Count |
|---|---|
| MK-7162 25 mg + Pembro 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 | 6 |
| MK-7162 50 mg + Pembro 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 | 6 |
| MK-7162 100 mg + Pembro 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 | 6 |
| MK-7162 200 mg + Pembro 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 | 15 |
| Total | 33 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Death | 6 | 4 | 5 | 14 |
| Overall Study | In survival phase status at study closure. Participant transferred to pembrolizumab extension study | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 0 | 1 | 1 | 1 |
Baseline characteristics
| Characteristic | MK-7162 25 mg + Pembro | MK-7162 50 mg + Pembro | MK-7162 100 mg + Pembro | MK-7162 200 mg + Pembro | Total |
|---|---|---|---|---|---|
| Age, Continuous | 60.0 Years STANDARD_DEVIATION 14.5 | 56.0 Years STANDARD_DEVIATION 14.2 | 61.7 Years STANDARD_DEVIATION 9.9 | 59.6 Years STANDARD_DEVIATION 12.8 | 59.4 Years STANDARD_DEVIATION 12.4 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 5 Participants | 6 Participants | 6 Participants | 12 Participants | 29 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 0 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 3 Participants | 5 Participants | 9 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 0 Participants | 0 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 3 Participants | 7 Participants | 20 Participants |
| Sex: Female, Male Female | 4 Participants | 4 Participants | 4 Participants | 8 Participants | 20 Participants |
| Sex: Female, Male Male | 2 Participants | 2 Participants | 2 Participants | 7 Participants | 13 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 6 / 6 | 4 / 6 | 5 / 6 | 14 / 15 |
| other Total, other adverse events | 6 / 6 | 6 / 6 | 6 / 6 | 15 / 15 |
| serious Total, serious adverse events | 1 / 6 | 3 / 6 | 3 / 6 | 5 / 15 |
Outcome results
Primary
Number of Participants Experiencing Dose-limiting Toxicities (DLTs) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 by the Investigator
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.
Time frame: Cycle 1 and Cycle 2 (Up to 6 weeks)
Population: 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.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-7162 25 mg + Pembro | Number of Participants Experiencing Dose-limiting Toxicities (DLTs) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 by the Investigator | 0 Participants |
| MK-7162 50 mg + Pembro | Number of Participants Experiencing Dose-limiting Toxicities (DLTs) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 by the Investigator | 0 Participants |
| MK-7162 100 mg + Pembro | Number of Participants Experiencing Dose-limiting Toxicities (DLTs) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 by the Investigator | 0 Participants |
| MK-7162 200 mg + Pembro | Number of Participants Experiencing Dose-limiting Toxicities (DLTs) as Assessed Using Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 by the Investigator | 5 Participants |
Primary
Number of Participants Who Discontinued Study Drug 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. 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.
Time frame: Up to Approximately 26 Months
Population: All participants who received at least one dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-7162 25 mg + Pembro | Number of Participants Who Discontinued Study Drug Due to an AE | 0 Participants |
| MK-7162 50 mg + Pembro | Number of Participants Who Discontinued Study Drug Due to an AE | 0 Participants |
| MK-7162 100 mg + Pembro | Number of Participants Who Discontinued Study Drug Due to an AE | 1 Participants |
| MK-7162 200 mg + Pembro | Number of Participants Who Discontinued Study Drug Due to an AE | 4 Participants |
Primary
Number of Participants Who Experienced an Adverse Event (AE)
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.
Time frame: Up to Approximately 27 Months
Population: All participants who received at least one dose of study treatment
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MK-7162 25 mg + Pembro | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
| MK-7162 50 mg + Pembro | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
| MK-7162 100 mg + Pembro | Number of Participants Who Experienced an Adverse Event (AE) | 6 Participants |
| MK-7162 200 mg + Pembro | Number of Participants Who Experienced an Adverse Event (AE) | 15 Participants |
Secondary
Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab
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.
Time frame: Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Days 1 & 15; and Cycle 3, Day 1
Population: All participants who were compliant with the study procedures and have available data from at least one treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-7162 25 mg + Pembro | Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Day 1, Cycle 3: MK-7162 + Pembrolizumab | 12200 hr*nM | Geometric Coefficient of Variation 27.7 |
| MK-7162 25 mg + Pembro | Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Day 15, Cycle 1: MK-7162 alone | 10300 hr*nM | Geometric Coefficient of Variation 37.3 |
| MK-7162 25 mg + Pembro | Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Day 1, Cycle 1: MK-7162 alone | 4400 hr*nM | Geometric Coefficient of Variation 36.5 |
| MK-7162 50 mg + Pembro | Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Day 1, Cycle 3: MK-7162 + Pembrolizumab | 20900 hr*nM | Geometric Coefficient of Variation 101.2 |
| MK-7162 50 mg + Pembro | Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Day 1, Cycle 1: MK-7162 alone | 8640 hr*nM | Geometric Coefficient of Variation 29.9 |
| MK-7162 50 mg + Pembro | Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Day 15, Cycle 1: MK-7162 alone | 19200 hr*nM | Geometric Coefficient of Variation 90.7 |
| MK-7162 100 mg + Pembro | Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Day 15, Cycle 1: MK-7162 alone | 47300 hr*nM | Geometric Coefficient of Variation 87.8 |
| MK-7162 100 mg + Pembro | Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Day 1, Cycle 1: MK-7162 alone | 20700 hr*nM | Geometric Coefficient of Variation 32.6 |
| MK-7162 100 mg + Pembro | Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Day 1, Cycle 3: MK-7162 + Pembrolizumab | 36100 hr*nM | Geometric Coefficient of Variation 117.8 |
| MK-7162 200 mg + Pembro | Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Day 1, Cycle 3: MK-7162 + Pembrolizumab | 10700 hr*nM | Geometric Coefficient of Variation 98.4 |
| MK-7162 200 mg + Pembro | Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Day 15, Cycle 1: MK-7162 alone | 118000 hr*nM | Geometric Coefficient of Variation 93.5 |
| MK-7162 200 mg + Pembro | Area Under the Concentration-Time Curve (AUC) From 0-8 Hours of MK-7261 Alone and in Combination With Pembrolizumab | Day 1, Cycle 1: MK-7162 alone | 31700 hr*nM | Geometric Coefficient of Variation 44.4 |
Secondary
Kynurenine (KYN) Biomarker Plasma Concentration
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.
Time frame: Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Day 1: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose
Population: All participants who were compliant with the study procedures and have available data from at least one treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, Predose | 1.9 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 1 Hr Postdose | 1.8 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, Predose | 1.8 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, Predose | 1.6 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 2 Day 1, Predose | 2.1 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, 4 Hr Postdose | 2.0 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 4 Hr Postdose | 2.0 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 1 Hr Postdose | 1.7 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 8 Hr Postdose | 1.7 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 15, PreDose | 2.0 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, 1 Hour (hr) Postdose | 1.9 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 2 Hr Postdose | 1.8 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 8 Hr Postdose | 1.8 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, 2 Hr Postdose | 2.0 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 2 Hr Postdose | 2.0 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 4 Hr Postdose | 1.8 μmol/L |
| MK-7162 25 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day1, 8 Hr Postdose | 1.8 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 4 Hr Postdose | 1.2 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 1 Hr Postdose | 1.6 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 8 Hr Postdose | 1.1 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 15, PreDose | 2.2 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 2 Day 1, Predose | 1.2 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, Predose | 1.6 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 8 Hr Postdose | 1.6 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, 4 Hr Postdose | 1.5 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day1, 8 Hr Postdose | 1.4 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, 1 Hour (hr) Postdose | 1.5 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 4 Hr Postdose | 1.6 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, Predose | 1.2 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, Predose | 1.5 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 1 Hr Postdose | 1.2 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 2 Hr Postdose | 1.6 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 2 Hr Postdose | 1.2 μmol/L |
| MK-7162 50 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, 2 Hr Postdose | 1.5 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 2 Day 1, Predose | 0.6 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, Predose | 2.3 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, 1 Hour (hr) Postdose | 2.2 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, 2 Hr Postdose | 2.2 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, 4 Hr Postdose | 2.1 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day1, 8 Hr Postdose | 2.0 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, Predose | 1.3 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 1 Hr Postdose | 1.3 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 2 Hr Postdose | 1.3 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 4 Hr Postdose | 1.3 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 8 Hr Postdose | 1.2 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, Predose | 1.4 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 1 Hr Postdose | 1.3 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 2 Hr Postdose | 1.4 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 4 Hr Postdose | 1.4 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 8 Hr Postdose | 1.4 μmol/L |
| MK-7162 100 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 15, PreDose | 1.5 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 1 Hr Postdose | 1.1 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 2 Hr Postdose | 1.0 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 1 Hr Postdose | 1.0 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, 1 Hour (hr) Postdose | 1.5 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 2 Hr Postdose | 1.1 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, Predose | 1.0 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day1, 8 Hr Postdose | 1.4 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, Predose | 1.7 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 4 Hr Postdose | 1.1 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, 4 Hr Postdose | 1.5 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 1, 2 Hr Postdose | 1.5 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 2 Day 1, Predose | 1.0 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 15, PreDose | 0.9 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, Predose | 1.1 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 8 Hr Postdose | 1.0 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 1 Day 15, 4 Hr Postdose | 1.1 μmol/L |
| MK-7162 200 mg + Pembro | Kynurenine (KYN) Biomarker Plasma Concentration | Cycle 3 Day 1, 8 Hr Postdose | 1.1 μmol/L |
Secondary
Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab
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.
Time frame: Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Days 1 and 15 and Cycle 3, Day 1
Population: All participants who were compliant with the study procedures and have available data from at least one treatment.
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MK-7162 25 mg + Pembro | Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Day 1 Cycle 1: MK-7162 alone | 902 nM | Geometric Coefficient of Variation 48 |
| MK-7162 25 mg + Pembro | Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Day 1 Cycle 3: MK-7162+ Pembrolizumab | 2140 nM | Geometric Coefficient of Variation 52.2 |
| MK-7162 25 mg + Pembro | Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Day15 Cycle 1: MK-7162 Alone | 1940 nM | Geometric Coefficient of Variation 38.3 |
| MK-7162 50 mg + Pembro | Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Day 1 Cycle 1: MK-7162 alone | 1750 nM | Geometric Coefficient of Variation 27.8 |
| MK-7162 50 mg + Pembro | Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Day 1 Cycle 3: MK-7162+ Pembrolizumab | 3120 nM | Geometric Coefficient of Variation 96.2 |
| MK-7162 50 mg + Pembro | Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Day15 Cycle 1: MK-7162 Alone | 3560 nM | Geometric Coefficient of Variation 64.1 |
| MK-7162 100 mg + Pembro | Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Day15 Cycle 1: MK-7162 Alone | 8910 nM | Geometric Coefficient of Variation 84.5 |
| MK-7162 100 mg + Pembro | Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Day 1 Cycle 1: MK-7162 alone | 4420 nM | Geometric Coefficient of Variation 28.2 |
| MK-7162 100 mg + Pembro | Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Day 1 Cycle 3: MK-7162+ Pembrolizumab | 6110 nM | Geometric Coefficient of Variation 100.9 |
| MK-7162 200 mg + Pembro | Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Day 1 Cycle 1: MK-7162 alone | 6550 nM | Geometric Coefficient of Variation 48.6 |
| MK-7162 200 mg + Pembro | Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Day 1 Cycle 3: MK-7162+ Pembrolizumab | 17800 nM | Geometric Coefficient of Variation 77.9 |
| MK-7162 200 mg + Pembro | Maximum Plasma Concentration (Cmax) of MK-7162 When Administered Alone and in Combination With Pembrolizumab | Day15 Cycle 1: MK-7162 Alone | 20600 nM | Geometric Coefficient of Variation 77 |
Secondary
Minimum Plasma Concentration (Cmin) of MK-7162
Blood samples were obtained at designated time points to determine the Cmin of MK-7162 in plasma.
Time frame: Pre-dose and at 1, 2, 4, and 8 hours post-dose on Cycle 1, Day 14
Population: All participants who were compliant with the study procedures and have available plasma data.
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| MK-7162 25 mg + Pembro | Minimum Plasma Concentration (Cmin) of MK-7162 | 1070 nM | Geometric Coefficient of Variation 73.1 |
| MK-7162 50 mg + Pembro | Minimum Plasma Concentration (Cmin) of MK-7162 | 1260 nM | Geometric Coefficient of Variation 219.9 |
| MK-7162 100 mg + Pembro | Minimum Plasma Concentration (Cmin) of MK-7162 | 3390 nM | Geometric Coefficient of Variation 130.3 |
| MK-7162 200 mg + Pembro | Minimum Plasma Concentration (Cmin) of MK-7162 | 13800 nM | Geometric Coefficient of Variation 177.3 |
Secondary
Objective Response Rate (ORR) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator
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.
Time frame: Up to approximately 28 months
Population: 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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| MK-7162 25 mg + Pembro | Objective Response Rate (ORR) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator | 0.0 Percentage of Participants |
| MK-7162 50 mg + Pembro | Objective Response Rate (ORR) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator | 16.7 Percentage of Participants |
| MK-7162 100 mg + Pembro | Objective Response Rate (ORR) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator | 0.0 Percentage of Participants |
| MK-7162 200 mg + Pembro | Objective Response Rate (ORR) Based on Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator | 0.0 Percentage of Participants |
Secondary
Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors
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)
Time frame: Up to approximately 28 months
Population: All participants who had follow up tumor imaging subsequent to initial progressive disease per RECIST 1.1 by investigator assessment
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| MK-7162 25 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iUPD | 80.0 Percentage of Participants |
| MK-7162 25 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iPR | 0.0 Percentage of Participants |
| MK-7162 25 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iCPD | 20.0 Percentage of Participants |
| MK-7162 25 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iSD | 0.0 Percentage of Participants |
| MK-7162 25 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iCR | 0.0 Percentage of Participants |
| MK-7162 50 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iSD | 0.0 Percentage of Participants |
| MK-7162 50 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iUPD | 60.0 Percentage of Participants |
| MK-7162 50 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iCPD | 40.0 Percentage of Participants |
| MK-7162 50 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iPR | 0.0 Percentage of Participants |
| MK-7162 50 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iCR | 0.0 Percentage of Participants |
| MK-7162 100 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iSD | 0.0 Percentage of Participants |
| MK-7162 100 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iCR | 0.0 Percentage of Participants |
| MK-7162 100 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iPR | 0.0 Percentage of Participants |
| MK-7162 100 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iUPD | 100.0 Percentage of Participants |
| MK-7162 100 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iCPD | 0.0 Percentage of Participants |
| MK-7162 200 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iUPD | 75.0 Percentage of Participants |
| MK-7162 200 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iPR | 0.0 Percentage of Participants |
| MK-7162 200 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iCR | 0.0 Percentage of Participants |
| MK-7162 200 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iSD | 0.0 Percentage of Participants |
| MK-7162 200 mg + Pembro | Overall Response Based on Immune Response Evaluation Criteria (iRECIST) In Solid Tumors | iCPD | 25.0 Percentage of Participants |
Secondary
Tryptophan (TRP) Biomarker Plasma Concentration
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.
Time frame: Cycle 1 Days 1 & 15: predose, 1, 2, 4 & 8 hours postdose; Cycle 2 Day 1: predose; Cycle 3 Day 1: predose, 1, 2, 4 & 8 hours postdose; Cycle 3 Day 15: predose
Population: All participants who were compliant with the study procedures and have available data from at least one treatment
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, 4 Hr Postdose | 1.0 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 2 Hr Postdose | 0.8 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15,8 Hr Postdose | 1.0 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, 1 Hr Postdose | 0.8 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 2 Day 1, Predose | 0.8 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day1, Predose | 0.7 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, Predose | 0.8 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cyle 3 Day 1, 8 Hr Postdose | 0.9 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 4 Hr Postdose | 0.9 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 8 Hr Postdose | 0.9 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 1 Hr Postdose | 0.7 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, 4 Hr Postdose | 0.9 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, Predose | 0.8 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, 1 Hr Postdose | 0.9 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, 2 Hr Postdose | 0.9 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, 2 Hr Postdose | 0.9 mg/dL |
| MK-7162 25 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 15, Predose | 0.8 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, 1 Hr Postdose | 0.7 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 8 Hr Postdose | 0.9 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, 1 Hr Postdose | 0.7 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day1, Predose | 0.8 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15,8 Hr Postdose | 0.8 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 2 Hr Postdose | 0.9 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, 4 Hr Postdose | 0.8 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cyle 3 Day 1, 8 Hr Postdose | 0.7 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 2 Day 1, Predose | 0.6 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, Predose | 0.8 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, Predose | 0.7 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 1 Hr Postdose | 0.8 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, 2 Hr Postdose | 0.8 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, 2 Hr Postdose | 0.8 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 4 Hr Postdose | 0.9 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 15, Predose | 0.6 mg/dL |
| MK-7162 50 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, 4 Hr Postdose | 0.8 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, 1 Hr Postdose | 0.5 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day1, Predose | 0.7 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 1 Hr Postdose | 0.6 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 2 Hr Postdose | 0.7 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 4 Hr Postdose | 0.7 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 8 Hr Postdose | 0.8 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, Predose | 0.6 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, 1 Hr Postdose | 0.6 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, 2 Hr Postdose | 0.6 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, 4 Hr Postdose | 0.7 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15,8 Hr Postdose | 0.7 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 2 Day 1, Predose | 0.7 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, Predose | 0.5 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, 2 Hr Postdose | 0.6 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, 4 Hr Postdose | 0.6 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cyle 3 Day 1, 8 Hr Postdose | 0.6 mg/dL |
| MK-7162 100 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 15, Predose | 0.6 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, 2 Hr Postdose | 0.6 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, 1 Hr Postdose | 0.7 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, 1 Hr Postdose | 0.7 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, Predose | 0.7 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 1 Hr Postdose | 0.6 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, 2 Hr Postdose | 0.7 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 8 Hr Postdose | 0.8 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 4 Hr Postdose | 0.8 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day1, Predose | 0.7 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, 4 Hr Postdose | 0.8 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 1, 2 Hr Postdose | 0.7 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 15, Predose | 0.6 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 2 Day 1, Predose | 0.6 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cyle 3 Day 1, 8 Hr Postdose | 0.8 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 3 Day 1, Predose | 0.7 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15,8 Hr Postdose | 0.7 mg/dL |
| MK-7162 200 mg + Pembro | Tryptophan (TRP) Biomarker Plasma Concentration | Cycle 1 Day 15, 4 Hr Postdose | 0.7 mg/dL |