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Copanlisib plus rituximab demonstrated superior efficacy relative to placebo plus rituximab in patients with relapsed marginal zone lymphoma (MZL), according to the results of a subgroup analysis of the CHRONOS-3 trial. These findings were presented by Muhit Özcan, MD, of Ankara University School of Medicine in Turkey, during the European Society for Medical Oncology (ESMO) Congress 2021.
CHRONOS-3 (ClinicalTrials.gov Identifier: NCT02367040) is a randomized, double-blind, placebo-controlled phase 3 study that previously demonstrated a 48% risk reduction in disease progression/death with the phosphoinositide 3-kinase (PI3K) inhibitor copanlisib plus rituximab compared with placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (iNHL).
The study included patients with relapsed iNHL who were progression- and treatment-free for 12 months or longer after rituximab-based therapy or 6 months or more if unwilling/unfit to receive chemotherapy. Patients were randomly assigned 2:1 to copanlisib plus rituximab (C+R) or placebo plus rituximab (P+R). Copanlisib (60 mg) or placebo was administered intravenously on days 1, 8, and 15 (28-day cycle); rituximab (375 mg/m2) was administered intravenously on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 3, 5, 7, and 9. The primary endpoint was progression-free survival (PFS).
Of 458 participants in CHRONOS-3, 66 patients with MZL were randomly assigned to the C+R arm and 29 to the P+R arm, with median ages of 66 years (range: 37-91) and 63 years (range: 46-76), respectively. MZL subtypes included nodal (39%), extranodal (37%), and splenic (24%).
At a median follow up duration of 18 months, C+R significantly reduced the risk of disease progression/death relative to P+R (median PFS, 22.1 vs 11.5 months; hazard ratio, 0.47; 1-sided P =.012). Objective response rate was significantly higher with C+R (76%, with a complete response rate [CRR] of 39%) compared with P+R (41%, with a CRR of 10%; P <.001). These findings appeared to be consistent across subtypes; however, the sample sizes were limited.
Median duration of response was 25.4 months for patients in the C+R arm and 9.3 months for those in the P+R arm, and median time to progression was 33.2 months and 11.5 months, respectively. The median overall survival was not evaluable.
The safety profile of C+R was consistent with that of each agent as monotherapy. The most common treatment-emergent adverse events (TEAEs; all grade/grade 3+) in the C+R arm were hyperglycemia (65%/54%), hypertension (54%/45%), diarrhea (32%/1.5%), and pyrexia (25%/5%). The most common TEAEs in the P+R arm were hyperglycemia (24%/10%), cough (24%/0%), and upper respiratory tract infection (24%/0%). TEAEs considered related to C/P included hyperglycemia (63%/24%) and hypertension (54%/17%). Pneumonitis was evaluated as an AE of interest and occurred in 9% of the C+R arm and 5% of the P+R arm. No grade 5 AEs occurred.
“In conclusion, copanlisib is the first PI3 kinase inhibitor to be safely combined with the rituximab in a phase three setting in patients with relapsed MZL, representing a potential new therapeutic strategy,” said Dr Özcan.
Disclosure: This research was supported by Bayer AG. Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Özcan M, Jin J, Szomor Á, et al. Copanlisib plus rituximab vs placebo plus rituximab in patients (pts) with relapsed marginal zone lymphoma (MZL) treated in the phase III CHRONOS-3 trial. Presented at: European Society for Medical Oncology (ESMO) Congress 2021 ; September 16-21, 2021. Abstract 826O.