Journal article
CHRONOS‐3: Randomized phase III study of copanlisib plus rituximab/placebo in relapsed indolent Non-Hodgkin Lymphoma (INHL)
Hematological Oncology, Vol.39(S2)
2021
Abstract
Introduction: Rituximab (R)-based therapies are standard for patients (pts) with relapsed advanced iNHL. Copanlisib (C) is a PI3K inhibitor approved as monotherapy for relapsed follicular lymphoma (FL) in pts who have had ≥2 prior systemic therapies. We report primary data from the Phase III CHRONOS-3 study of treatment with C+R vs placebo (P)+R in relapsed iNHL (NCT02367040).
Methods: Pts with relapsed iNHL who were progression-free and treatment-free for ≥12 months (mo) after last R-based therapy or unwilling/unfit to receive chemotherapy were randomized 2:1 to receive C+R or P+R. C 60 mg/P was given i.v. on days 1, 8, and 15 (28-day cycle); R 375 mg/m2 was given i.v. on days 1, 8, 15, and 22 during cycle 1 and on day 1 of cycles 3, 5, 7, and 9. Primary endpoint: centrally assessed progression-free survival (PFS). Secondary endpoints: objective response rate (ORR), duration of response, complete response rate (CRR), overall survival (OS), and treatment-emergent adverse events (TEAEs). The data cut-off date was August 31, 2020.
Results: 307 pts were randomized to C+R and 151 to P+R. FL was the most common lymphoma histology subtype (60.0%), followed by marginal zone (MZL, 20.7%), small lymphocytic (SLL, 10.9%), and lymphoplasmacytic/Waldenström macroglobulinemia (LPL/WM, 8.3%). Median age was 63 years (range 28-91). With a median follow-up of 19.2 mo, the primary study endpoint was met: C+R significantly reduced the risk of disease progression/death vs P+R (hazard ratio [HR] 0.52 [95% CI 0.39, 0.69]; 1-sided p = 0.000002); median PFS was 21.5 mo (95% CI 17.8, 33.0) vs 13.8 mo (95% CI 10.2, 17.5), respectively. Reductions in risk of progression/death were seen across all histology subtypes (HR [95% CI]): FL 0.580 [0.404, 0.833]; MZL 0.475 [0.245, 0.923]; SLL 0.243 [0.111, 0.530]; LPL/WM 0.443 [0.160, 1.231]. ORRs were 80.8% (CRR 33.9%) for C+R and 47.7% (CRR 14.6%) for P+R. Higher ORRs and CRRs were seen across all iNHL subtypes with C+R treatment. Median OS was not estimable. Most common TEAEs (all grades [G]/G3+) in pts receiving C+R were hyperglycemia (69.4%/56.4%), hypertension (49.2%/39.7% [all G3]), and diarrhea (33.6%/4.9% [all G3]). For pts receiving P+R, hyperglycemia (23.3%/8.2% [all G3]), hypertension (19.2%/8.9% [all G3]), neutropenia (16.4%/12.3%), and upper respiratory tract infection (16.4%/0%) were the most common TEAEs. Serious adverse events were higher with C+R (47.2%) vs P+R (18.5%). G5 TEAEs occurred in 6 pts (2.0%) receiving C+R (1 [0.3%] deemed treatment-related; pneumonitis) and 1 (0.7%) receiving P+R.
Conclusions: C+R demonstrated broad and superior efficacy vs P+R in pts with relapsed iNHL. The safety profile of C+R was manageable and consistent with C and R as monotherapy. Copanlisib is the first PI3K inhibitor to be safely combined with R in relapsed iNHL, representing a potential new therapy option for relapsed iNHL across all subtypes.
Details
- Title
- CHRONOS‐3: Randomized phase III study of copanlisib plus rituximab/placebo in relapsed indolent Non-Hodgkin Lymphoma (INHL)
- Authors/Creators
- P.L. Zinzani (Author/Creator)M. Capra (Author/Creator)M. Özcan (Author/Creator)F. Lv (Author/Creator)W. Li (Author/Creator)E. Yañez (Author/Creator)K. Sapunarova (Author/Creator)T. Lin (Author/Creator)J. Jin (Author/Creator)W. Jurczak (Author/Creator)A. Hamed (Author/Creator)M.C. Wang (Author/Creator)R. Baker (Author/Creator)I. Bondarenko (Author/Creator)Q. Zhang (Author/Creator)J. Feng (Author/Creator)K. Geissler (Author/Creator)M. Lazaroiu (Author/Creator)G. Saydam (Author/Creator)Á. Szomor (Author/Creator)K. Bouabdallah (Author/Creator)R. Galiulin (Author/Creator)T. Uchida (Author/Creator)L. Mongay Soler (Author/Creator)A. Cao (Author/Creator)F. Hiemeyer (Author/Creator)A. Mehra (Author/Creator)B.H. Childs (Author/Creator)Y. Shi (Author/Creator)M.J. Matasar (Author/Creator)
- Publication Details
- Hematological Oncology, Vol.39(S2)
- Publisher
- Wiley
- Identifiers
- 991005541766107891
- Copyright
- © 2021 John Wiley & Sons Ltd.
- Murdoch Affiliation
- Western Australian Centre for Thrombosis and Haemostasis
- Language
- English
- Resource Type
- Journal article
- Additional Information
- Supplement: 16th International Conference on Malignant Lymphoma, Virtual Edition, 18–22 June, 2021
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