Dr Christenson on the Safety of Copanlisib Plus Nivolumab in Pretreated MSS mCRC

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

Efficacy data presented at the 2024 AACR Annual Meeting showed copanlisib in combination with nivolumab exhibited durable responses in patients with MSS mCRC harboring PIK3Ca mutations, meeting the primary end point in the PIK3Ca-mutated cohort. In the PIK3Ca-mutated cohort (n = 22), 3 patients experienced a partial response (PR), and 2 patients had stable disease. The 3 responders experienced a progression-free survival (PFS) of approximately 24 months. In the PIK3Ca wild-type cohort (n = 17), 1 patient had a PR, and 4 patients had stable disease. The PFS for the lone responder was approximately 30 months.

Regarding the safety, Christenson notes that the combination was generally well tolerated, and investigators observed some expected toxicities associated with the known toxicity profile of PI3K inhibitors.

In the PIK3Ca-mutated and the PIK3Ca wild-type cohorts, the rates of grade 3 or higher adverse effects (AEs) were 48% and 67%, respectively. Common grade 3 or higher AEs included hypertension (PIK3Ca-mutated cohort, 43%; PIK3Ca wild-type cohort, 33%), maculopapular rash (10%; 17%), gastrointestinal disorders (10%; 8%), increased aspartate aminotransferase (0%; 8%), and hyperglycemia (5%; 17%).

The safety findings align with the class effect of PI3K inhibitors, which are known to cause elevated blood pressure, Christenson says. Despite being rare, hyperglycemia remained a noted toxicity and was closely monitored, he adds.

The combination of copanlisib and nivolumab was manageable in terms of safety, with no unexpected or severe AEsoutside of the typical profile associated with PI3K inhibition, he continues. The findings suggest that this combination could be a viable treatment option for a subset of patients with MSS mCRC, though ongoing monitoring for hypertension and hyperglycemia is essential, he concludes.