J1677- A Phase 1/2a Study of BMS-986179 Administered Alone and in Combination with Nivolumab (BMS-936558) in Subjects with Advanced Solid Tumors
Johns Hopkins Kimmel Cancer Center in Baltimore
1. assess the safety and tolerability of BMS-986179 administered alone and/or in combination with nivolumab.2. To characterize the pharmacodynamic (PD) activity of BMS-986179 administered alone and in combination with nivolumab. 3. To assess the preliminary anti-tumor activity of BMS-986179 in combination with nivolumab as measured by objective response rate (ORR), duration of response (DOR), and progression-free survival rate (PFSR). 4.To characterize the pharmacokinetics (PK) and immunogenicity of BMS-986179 administered alone and in combination with nivolumab. 5. To characterize immunogenicity of nivolumab when administered in combination with BMS-986179.
Subjects must have histologic or cytologic confirmation of a malignancy that is advanced (metastatic and/or unresectable) with measureable disease per RECIST v1.1 and have at least 1 lesion that is biopsy-accessible. Subjects must have received, and then progressed or been intolerant to, at least 1 standard treatment regimen in the advanced or metastatic setting. All solid tumor histologies will be permitted except for subjects with primary CNS tumors or with CNS metastases as the only site of active disease
Part 1A: Various dose levels (150 through 1600 mg), provided in Table 1, may be evaluated for BMS-986179 weekly (Q1W) during monotherapy lead-in followed by combination therapy with nivolumab every 2 weeks (Q2W) and BMS-986179 Q1W. The maximum dose studied may be lower than 1600 mg and will be determined by the human safety data, PK, and PD of the prior dose levels. The overall DLT observation period will be 6 weeks (through Day 42) from the initial dose of BMS-986179. Part 1B: The PD substudy will provide additional information pertaining to the combination dose and dose regimens of BMS-986179 and nivolumab for further study in Part 2. The dose schedules studied in Part 1B may include Q2W and every 3 weeks (Q3W). Part 2: The purpose of the cohort expansion study is to gather additional safety, tolerability, and PD information, in addition to preliminary efficacy information, for the combination of BMS-986179 and nivolumab.Treatment during the monotherapy lead-in period (Part 1A only) will continue for 2 weeks; treatment during the combination therapy period will continue for up to 24 weeks in each study part.Subjects in each study part will complete up to 4 periods in the study: screening, treatment, safety follow-up, and response/survival follow-up.
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