Copanlisib in combination with nivolumab formicrosatellite stable colorectal cancer: a phase 1/2 trial.

PIK3CA is mutated in ~15% of colorectal cancers (CRC). PI3K regulates immunity, inhibition potentially enhances anti-tumor immunity. We launched a phase 1/2 trial of copanlisib (PIK3CA inhibitor) and nivolumab (anti-PD-1) in metastatic microsatellite stable CRC (NCT03711058): Cohort A: PIK3CAwt (n = 17) and Cohort B: PIK3CAmut (n = 22). Copanlisib/nivolumab is well tolerated with recommended phase 2 dose of nivolumab 480 mg day 1 and copanlisib 60 mg days 1/8/15 of a 28-day cycle. Primary endpoint of objective response rate at 6 months was not met with Cohort A: 0/17 and Cohort B: 2/22 having 6-month treatment response. Secondary endpoints are median progression-free survival (Cohort A: 1.7 months; Cohort B: 1.6 months), median overall survival (Cohort A: 8.5 months; Cohort B: 6.7 months), duration of response (Cohort A: 13.1 months; Cohort B: 17 months) and 6-month disease control rate (Cohort A: 2/17; Cohort B: 3/22). Secondary endpoints were not statistically different between these cohorts.