Trial Outcomes & Findings for Study of MK-4166 and MK-4166 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4166-001) (NCT NCT02132754)

Of 116 participants that were non-randomly allocated to treatment, 113 participants received treatment and were evaluable for all analyses.

Study of MK-4166 and MK-4166 in Combination With Pembrolizumab (MK-3475) in Participants With Advanced Solid Tumors (MK-4166-001)

DLT's were assessed during the first cycle (21 days) for each dose level and included the following if assessed by the Investigator to be possibly, probably or definitely related to MK-4166 or MK-4166 plus pembrolizumab combination: Grade 4 non-hematologic toxicity; Grade 4 hematologic toxicity lasting ≥7 days, except thrombocytopenia (Grade 4 thrombocytopenia of any duration or Grade 3 thrombocytopenia if associated with bleeding); Grade 3 non-hematologic toxicity lasting \>3 days despite optimal supportive care; Grade 3 nausea, vomiting or diarrhea if \>3 days despite optimal supportive care; any Grade 3 or Grade 4 non-hematologic laboratory abnormality if medical intervention is required or if leading to hospitalization or if persisting for \>1 week; febrile neutropenia Grade 3 or Grade 4; any drug-related AE which caused participant to discontinue treatment during Cycle 1; Grade 5 toxicity; any treatment-related toxicity which caused a \>2 week delay in initiation of Cycle 2.

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the number of participants experiencing an AE was assessed and reported by arm (MK-4166 monotherapy and MK-4166 plus pembrolizumab combination therapy) as well as by dose cohort.

An AE was defined as any untoward medical occurrence in a participant administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. An AE could therefore be any unfavourable and unintended sign, symptom, or disease temporally associated with the use of a medicinal product or protocol-specified procedure, whether or not considered related to the medicinal product or protocol-specified procedure. Any worsening (i.e., any clinically significant adverse change in frequency and/or intensity) of a pre-existing condition that was temporally associated with the use of the Sponsor's product was also an AE. Per protocol, the number of participants discontinuing study treatment due to AEs was assessed and reported by arm (MK-4166 monotherapy and MK-4166 plus pembrolizumab combination therapy) as well as by dose cohort.

Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 Cmax. Cmax was defined as the maximum concentration of MK-4166 reached. MK-4166 Cmax was reported by dose cohort. Per protocol, percent geometric coefficient of variation (%GCV) values were not reported for cohorts with n\<2 participants.

Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 Tmax. Tmax was defined as time to the maximum concentration of MK-4166 reached. MK-4166 Tmax was reported by dose cohort.

Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 t½. t½ was defined as the time required to divide the MK-4166 plasma concentration by two after reaching pseudo-equilibrium, following a single dose of MK-4166. MK-4166 t½ was reported by dose cohort. Per protocol, % GCV values were not reported for cohorts with n\<2 participants.

Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 AUC0-21. AUC0-21 was defined as the area under the concentration-time curve of MK-4166 from time zero to 21 hours after dosing. MK-4166 AUC0-21 was reported by dose cohort. Per protocol, % GCV values were not reported for cohorts with n\<2 participants.

Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 AUC0-last. AUC0-last was defined as the area under the concentration-time curve of MK-4166 from time zero to the last quantifiable sample. MK-4166 AUC0-last was reported by dose cohort. Per protocol, % GCV values were not reported for cohorts with n\<2 participants.

Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 AUC0-inf. AUC0-inf was defined as the area under the concentration-time curve of MK-4166 from time zero to infinity. MK-4166 AUC0-inf was reported by dose cohort. Per protocol, % GCV values were not reported for cohorts with n\<2 participants.

Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 CL. CL was defined as the volume of plasma from which MK-4166 is eliminated per unit time following IV MK-4166 administration. MK-4166 CL was reported by dose cohort. Per protocol, % GCV values were not reported for cohorts with n\<2 participants.

Blood samples were collected at pre-specified time points during Cycles 1-4 and plasma isolated for analysis of MK-4166 V. V was defined as the theoretical volume that would be necessary to contain the total amount of administered MK-4166 at the same concentration that it is observed in the blood plasma. MK-4166 V was reported by dose cohort. Per protocol, % GCV values were not reported for cohorts with n\<2 participants.