For Parts B, C, D and E scans will be collected centrally to be reviewed in real time by BICR. Abbreviations: BICR = blinded independent central review; DLT = dose-limiting toxicity; DOR = duration of response; ICOS-L = Inducible T- cell COStimulator ligand; ORR = objective response r ate; PFS = progression-free surviv al; PK = pharmacokinetics; TIL = tumor-infiltrating lymphocytes. Overall Design: •This is a Phase 1/2, open-label study of BMS-986226 administered as a monotherapy or in combination with either nivolumab or ipilimumab in participants with advanced solid tumors. The study will be c onducted in 3 parts: 1) dose-escalatio n monotherapy (Preliminary Safety Cohorts and Part A); 2) dose-escalation combination therapy with either nivolumab (Part B) or ipilimumab (Part C); 3) a dose expansion phase with either nivolumab (Part D) or ipilimumab (Part E). •All participants receiving treatment wi th BMS-986226 in all study parts are reco mmended to receive premedication as described in Section 7.1 of the protocol. Revised Protocol No.: 04 Date: 31-May-2019 12 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS •Monotherapy consists of 2 different cohorts as follows: −Preliminary Safety Cohorts with BMS-986226 administered as monotherapy at 2 mg and 8 mg once every 4 weeks (Q4W) for 24 weeks −Part A, with BMS-986226 administered at 25 mg, 80 mg, 200 mg, 400 mg, and 800 mg Q4W for 24 weeks •The study will fi rst evaluate the safety and tolerability of BMS- 986226 administered Q4W, given alone, based on dose-limiting toxicities (DLTs), guided by a Bayesian Logistic Regression Model (BLRM) employing the es calation with overdose control principle. •Parts B and C consist of different combination cohorts comprising: −B1: BMS-986226 administered every 12 weeks (Q12W) + nivolumab 480 mg Q4W at three dose levels of BMS-986226. −B2: BMS-986226 Q4W + nivolumab 480 mg Q4W at up to three dose levels of BMS-986226 evaluated in part B1. −C1: BMS-986226 Q12W + ipilimumab 3 mg/ kg Q4W at three dos e levels of BMS-986226. −C2: BMS-986226 Q4W + ipilimumab 3 mg/kg Q4W at up to three dose levels of BMS-986226 evaluated in part C1. •Parts B1 and C1 will enroll concurrently. Parts B2 and C2 will enroll if additional safety, PK, or PD data is required to optimize dose and/or schedule selection, and can enroll concurrently with B1 and C1. •BMS-986226 will be adminis tered as a single ag ent (Preliminary Safety Cohorts and Part A), in combination with either nivolumab (Part B or Part D) or ipilimumab (Part C or Part E) in disease-restricted populations as follows: −Preliminary Safety Cohorts and Part A: CC, CRC, HNSCC, MEL, NSCLC, RCC, PRC, TNBC and UCC −Parts B and C: CC, CRC, HNSCC, MEL, NSCLC, RCC, PRC, TNBC and UCC −Parts D and E: To be determined based on safe ty, tolerability, PK, and PD data from Parts A, B, and C Starting dose selection of BMS-986226 for the combination therapy cohorts will be one dose level lower than the highest monotherapy dose (Part A) that has cleared the DLT period. Subsequent doses of BMS-986226 will be determined base d on all available safety (clinical and laboratory) and PK data, as well as changes in pe ripheral target engagement markers (eg, ICOS downregulation on T cells and ICOS + B cells) previous and completed portions of current cohorts, and BLRM-Copula model. •The Preliminary Safety Cohorts consists of a single participant per dose level with BMS-986226 administered as monotherapy at 2 mg or 8 mg Q4W for up to 24 weeks of study treatment. Additional participants may be enro lled in the Preliminary Safety Cohorts per dose level as early as 5 days after the first participant is treated at each dose level to gather additional information on the safety, PK, and pharmacodynamic (PD) profile. The DLT period will be 28 days (4 weeks) in the Preliminary Safety Cohorts. Once the safety (during the 4 weeks DLT period) of 2 mg and 8 mg of BMS-986226 has been established in a single, independent Revised Protocol No.: 04 Date: 31-May-2019 13 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS participant per dose, Part A will start. Intra-p articipant dose escalation is only allowed in the Preliminary Safety Cohorts as follows: −Once the observation period of 4 weeks for 8 mg is completed, participant(s) treated at 2 mg may be offered the possibility to dose escalate at 8 mg. −Once the DLT period of 5 weeks for 25 mg is completed, participant(s) treated at 2 mg that escalated to 8 mg or participant(s) treated with 8 mg may be offered the possibility to dose escalate at 25 mg. •Part A consists of a multiple ascending dose schema that will evaluate the following dose levels of BMS-986226: 25 mg, 80 mg, 200 mg, 400 mg, and 800 mg. Enrollment in the next dose level can begin after at least 2 evaluable participants have completed 5 weeks of therapy (during the DLT evaluation) at the preceding dos e level and the available safety data has been reviewed. Up to approximately 34 par ticipants with the tumor types listed above may be treated during this part of the study (Preliminary Safety Cohorts and Part A). •Part B1 and Part B2 are dose escalation combination cohorts that consists of BMS-986226 administered in combination with nivolumab for duration of 2 years in the disease-restricted populations listed a bove. Part B1 is a combination cohort that consist of BMS-986226 administered every 12 weeks (Q12W) + nivolu mab 480 mg Q4W. Part B2 is a combination cohort that consists of BMS-986226 Q4W + nivolumab 480 mg Q4W at a dose level of BMS-986226 tested in Part B1. Up to 3 differe nt dose levels of BMS-986226 will be tested in Part B1, as determined by safety, PK and PD data. The starting dose level used in combination with nivolumab (Part B) will be one dose level lower than a monotherapy (Part A) dose that has cleared the DLT period. At each dose level, approximately 6 evaluable participants will be treated, where a sentinel pa rticipant will be e nrolled in Part B1 (BMS-986226 Q12W + nivolumab 480 mg Q4W) and observed for 5 days before additional participants in Part B1 at the same dose level receive study treatment. Part B2 (BMS-986226 Q4W + nivolumab 480 mg Q4W) will be opened at dose levels evalu ated in Part B1. A pproximately 6-12 evaluable participants will be treated per cohort, to better characterize safety, PK, and PD of the combination. Part B2 will be utilized to provide a more granular assessment of safety and PD of BMS-986226. More than 1 dose level (no more than 3 different dose levels) may be enrolled, should additional safety, PK, and PD data be needed. Once the safety (during the DLT evaluation) of a combination of BMS-986226 and nivolumab has been established and a recommended BMS-986226 dose regimen has been selected for Part D, additional participants (up to 6 additional evaluable participants) may be treated at the recommended dose to better characterize the safety, PK, and PD profile. •Part C1 and Part C2 are dose escalation combination cohorts that consist of BMS-986226 administered in combination with ipilimumab for dur ation of 2 years in the disease-restricted populations listed above. Part C1 is a combinatio n cohort that consists of BMS-986226 administered every 12 weeks (Q12W) + ipilimumab 3 mg/kg Q4W. Part C2 is a combination cohort that c onsists of BMS-986226 Q4W + ipilimumab 3 mg/kg Q4W at a dose level of BMS- 986226 tested in Part C1. Part C1 aims to determine the kinetics of ICOS receptor downregulation and re-expression (and/or change in selected target engagement/ ) following administration of BMS- 986226 Q12W in combinat ion with ipilimumab administered Q4W for a duration of 2 years. Continuous evaluation of toxicity events in the combination cohort will be performed throughout the enrollment. Up to 3 different dose levels of BMS-986226 w ill be tested in Part C1, as determined by safety, PK and PD data. At each Revised Protocol No.: 04 Date: 31-May-2019 14 Approved 5.0 v Approved 1.0 v Clinical Protocol CA021002 BMS-986226 anti-ICOS dose level, approximately 6 evaluable participants will be treated, where a sentinel participant will be enrolled in Part C1 (BMS-986226 Q12W + ipilimumab 3mg/kg Q4W) and observed for 5 days before additional participants in Part C1 at the same dose level receive study treatment. Part C2 (BMS-986226 Q4W + ipilimumab 3 mg/kg Q4W) will be opened at dose levels evaluated in Part C1. Approximately 6-12 evaluable participants will be treated per dose cohort, to better ch aracterize safety, PK, and PD of the co mbination. Part C2 will be utilized to provide a more granul ar assessment of safety and PD of BMS-986226. More than 1 dose level (no more than 3 different dose levels) may be enrolled, should additional safety, PK, and PD data be needed. Once the safety (during the DLT evaluation) of a combination of BMS-986226 and ipilimumab has been established and a recommended BMS-986226 dose regimen has been selected for Part E, additional participants (up to 6 additional evaluable participants) may be treated at the recommended dose to better characterize the safety, PK, and PD profile. •Part D and Part E are cohort expansion that consist of BMS-986226 in combination with either nivolumab (Part D) or ipilimumab (Part E ). Continuous evaluation of toxicity events in the cohort expansions will be performed throughout enrollment in the expansion cohorts.