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 safety

 (NCT03711058) evaluating copanlisib (Aliqopa) in combination with nivolumab (Opdivo) in patients with pretreated, microsatellite stable (MSS), unresectable or metastatic colorectal cancer (mCRC).

 showed copanlisib in combination with nivolumab exhibited durable responses in patients with MSS mCRC harboring 

 mutations, meeting the primary end point in the 

-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 

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.

 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 (

 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.

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Eric S. Christenson, MD, discusses the safety of copanlisib plus nivolumab in pretreated, PIK3Ca-mutated microsatellite stable, unresectable or metastatic colorectal cancer.

Eric S. Christenson, MD, discusses efficacy data for copanlisib plus nivolumab in patients with pretreated, MSS metastatic colorectal cancer.

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 

 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.

-mutated MSS mCRC (n = 22), 3 patients achieved a partial response (PR). Two additional patients with 

-mutated mCRC had stable disease (SD). The trial met its primary end point of overall response rate at 6 months in the 

-mutant cohort since responses were observed in at least 3 patients.

 wild-type cohort (n = 17), 1 patient experienced a PR. Although this patient did not harbor a 

 amplification was detected, which may have been why this patient responded to treatment, according to Christenson. Notably, 4 other patients in the 

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. 

Eric S. Christenson, MD

Articles

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

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