Copanlisib Combo Prolongs PFS in Phase 3 Study of Indolent Non-Hodgkin Lymphoma

The primary end point of prolonged progression-free survival (PFS) in the phase 3 CHRONOS-3 study (NCT02367040) was met with copanlisib (Aliqopa) in combination with rituximab (Rituxan) as treatment of patients with indolent non-Hodgkin lymphoma (iNHL), although the study population predominantly included patients with follicular lymphoma (FL) or marginal zone lymphoma (MZL), Bayer announced in a press release.

“Indolent forms of NHL are a heterogenous group of malignancies characterized by a chronic pattern of remissions and recurrences. For iNHL patients with disease progression who are in need of treatment, there are few approved treatment options,” said Scott Z. Fields, MD, senior vice president and head of Oncology Development at Bayer, in a statement. “The positive results from CHRONOS-3 demonstrate the potential clinical benefit of copanlisib in combination with rituximab, to address the unmet medical need in these patients.”

The randomized, double-blind, placebo-controlled CHRONOS-3 clinical trial aimed to evaluate whether the combination of copanlisib plus rituximab is superior to placebo and rituximab in extending PFS as treatment of patients with relapsed iNHL following at least 1 prior rituximab therapy. The safety appeared generally consistent with prior findings on the individual agents in the combination, and the study did not demonstrate any new safety signals.

The findings from this trial will be presented at an upcoming medical meeting, and the company plans to discuss these data with health authorities worldwide.

Secondary end points in the study included objective tumor response, duration of response (DOR), complete response (CR), time to progression, and overall survival (OS), among others. To be included in the study, patients had to be at least 18 years old with an ECOG performance status of ≤ 2 and a life expectancy of at least 3 months. Patients had to have either FL grade 1, 2, or 3a, small lymphocytic lymphoma, lymphoplasmacytic lymphoma/Waldenström macroglobulinemia, or MZL, and they had to have relapsed after the last rituximab-, rituximab biosimilar-, or anti-CD20 monoclonal antibody-containing regimen, and they were required to have adequate baseline laboratory values no more than 7 days prior to initiating study treatment.

Patients were excluded from the study if they had FL grade 3b or transformed disease, nor a progression-free interval of less than 12 months since the last rituximab-, rituximab biosimilars-, or anti-CD20 monoclonal antibody-containing regimen. Patients also could panpanpanot have a history or concurrent condition of interstitial lung disease, known lymphomatous involvement of the central nervous system, a known history of human immunodeficiency virus, or hepatitis B or C.

Copanlisib received an accelerated approval from the FDA in 2017 for the treatment of adult patients with relapsed FL who had received at least 2 prior systemic therapies, based on the findings from the phase 2 CHRONOS-1 study. The approval was based on the data for objective response rate (ORR), and continued approval of this therapy is contingent on verification and description of the clinical benefit observed in a confirmatory study.

The ORR in CHRONOS-1 was 59% (95% CI, 49-68), which included 14% CRs. According to updated 2-year follow-up from the analysis, the ORR was 59% (95% CI, 49-68), including 20% CRs.

The agent was also previously granted a Breakthrough Therapy designation from the FDA for the treatment of adult patients with relapsed MZL who received at least 2 prior lines of therapy. The designation was based on the data from CHRONOS-1, in which 23 patients with MZL achieved an ORR of 69.6% in the primary analysis, and a follow-up analysis at 18 months demonstrated an ORR of 78.3%.

Copanlisib is an intravenous PI3K inhibitor with predominant activity against the PI3K-alpha and delta isoforms, as well as those expressed in malignant B cells.

_References

_{Aliqopa™ (copanlisib) in combination with rituximab meets primary endpoint in patients with relapsed indolent non-hodgkin's lymphoma. News Release. Bayer. October 14, 2020. Accessed October 15, 2020. https://bwnews.pr/379WKfC}