Dr Christenson on Copanlisib Plus Nivolumab in Pretreated PIK3Ca+ MSS mCRC

Eric S. Christenson, MD, assistant professor of oncology, Johns Hopkins Medicine, discusses findings from a phase 1/2a trial (NCT03711058) of copanlisib (Aliqopa) in combination with nivolumab (Opdivo) in patients with pretreated, microsatellite stable (MSS), unresectable or metastatic colorectal cancer (mCRC).

The trial evaluated the combination in patients with relapsed/refractory solid tumors, and an expansion study was initiated to further investigate the regimen as treatment in the third line or later for patients with relapsed/refractory MSS mCRC. For the expansion portion, patients with pretreated MSS mCRC were assigned to 1 of 2 cohorts based on PIK3Ca mutation status. In the MSS mCRC cohorts, at least 2 prior lines of systemic therapy were required, including a fluoropyrimidine-, oxaliplatin-, and irinotecan-containing regimen.

Findings presented at the 2024 AACR Annual Meeting demonstrated that among patients with PIK3Ca-mutated MSS mCRC (n = 22), 3 patients achieved a partial response (PR). Two additional patients with PIK3Ca-mutated mCRC had stable disease (SD). The trial met its primary end point of overall response rate at 6 months in the PIK3Ca-mutant cohort since responses were observed in at least 3 patients.

In the PIK3Ca wild-type cohort (n = 17), 1 patient experienced a PR. Although this patient did not harbor a PIK3Ca mutation, a PIK31R amplification was detected, which may have been why this patient responded to treatment, according to Christenson. Notably, 4 other patients in the PIK3Cawild-type cohort had SD.

Among the 4 responders between the 2 cohorts, all remained on treatment for more than 24 months, which is notable for patients with MSS mCRC being treated in the third-line setting or later, Christenson says. Although copanlisib plus nivolumab elicited PRs in only a minority of patients, that subgroup experienced a significant clinical benefit, Christenson continues. To maximize the impact of this study, finding ways to better identify patients who may derive benefit from treatment with this combination will be crucial, Christenson concludes.