826O - Copanlisib plus rituximab vs placebo plus rituximab in patients (pts) with relapsed marginal zone lymphoma (MZL) treated in the phase III CHRONOS-3 trial

Background

The randomized, double-blind, placebo-controlled phase III CHRONOS-3 study (NCT02367040) showed a 48% risk reduction in disease progression/death with the PI3K inhibitor copanlisib + rituximab (C+R) vs placebo (P)+R in pts with relapsed indolent non-Hodgkin lymphoma (iNHL). We report a subset analysis in pts with MZL.

Methods

Pts with relapsed iNHL progression- and treatment-free for ≥12 months (mo) after R-based therapy or ≥6 mo if unwilling/unfit to receive chemotherapy were randomized 2:1 to C+R or P+R. C 60 mg/P was given i.v. on days (d) 1, 8, and 15 (28-d cycle); R 375 mg/m² was given i.v. on d 1, 8, 15, and 22 of cycle 1 and d 1 of cycles 3, 5, 7, and 9. Primary endpoint was centrally assessed progression-free survival (PFS).

Results

Of 458 pts in CHRONOS-3, 66 with MZL were randomized to C+R and 29 to P+R. MZL subtypes included nodal (39%), extranodal (37%), and splenic (24%). With a median follow-up of 18.0 mo, C+R significantly reduced the risk of disease progression/death vs P+R; objective response rate (ORR) improved with C+R (Table). Median duration of response was 25.4 mo for C+R vs 9.3 mo for P+R; median time to progression was 33.2 mo vs 11.5 mo. Median overall survival was not evaluable (NE). Most common treatment-emergent adverse events (TEAEs; all grade/grade 3+) with C+R were hyperglycemia (65%/54%) and hypertension (54%/45%). Most common TEAEs with P+R were hyperglycemia (24%/10%), cough (24%/0%) and upper respiratory tract infection (24%/0%). Serious TEAEs were higher with C+R (57%) vs P+R (28%). TEAEs deemed related to C/P included hyperglycemia (63%/24%) and hypertension (54%/17%). Table: 826O

Primary efficacy evaluation for PFS based on unstratified log-rank test and unstratified Cox proportional hazard model

Conclusions

C+R showed superior efficacy vs P+R in pts with relapsed MZL, including nodal MZL. The safety profile of C+R was consistent with C and R as monotherapy. Copanlisib is the first PI3K inhibitor to be safely combined with R in a phase III setting in pts with relapsed MZL and represents a new therapeutic strategy.

Clinical trial identification

NCT02367040.

Editorial acknowledgement

Writing support by Ryan Staudt, PhD, Complete HealthVizion.

Legal entity responsible for the study

Bayer AG.

Funding

Bayer AG.

Disclosure

M. Özcan: Financial Interests, Personal, Other, Honoraria: Amgen; Non-Financial Interests, Personal, Other, Travel support: Amgen; Non-Financial Interests, Personal, Other, Travel support: Bristol Myers Squibb; Financial Interests, Personal, Other, Financial relationships: Abdi İbrahim; Financial Interests, Personal, Other, Financial relationships: Jazz Pharmaceuticals; Financial Interests, Personal, Other, Financial relationships: Sanofi; Financial Interests, Personal, Research Grant: AbbVie; Non-Financial Interests, Personal, Other, Travel support: AbbVie; Financial Interests, Personal, Research Grant: Archigen Biotech; Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Research Grant: Celgene; Financial Interests, Personal, Research Grant: F. Hoffmann-La Roche Ltd.; Non-Financial Interests, Personal, Other, Travel support: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Other, Travel support: Janssen; Financial Interests, Personal, Research Grant: MSD; Financial Interests, Personal, Research Grant: Takeda. P. Panayiotidis: Financial Interests, Personal, Other, Honoraria: Genesis; Financial Interests, Personal, Other, Honoraria: Gilead; Financial Interests, Personal, Other, Honoraria: Roche; Financial Interests, Personal, Other, Honoraria: Takeda; Financial Interests, Personal, Research Grant: Genesis; Financial Interests, Personal, Research Grant: Roche; Financial Interests, Personal, Research Grant: Takeda. L. Mongay Soler: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare Pharmaceuticals, Inc. A. Cao: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare Pharmaceuticals, Inc. F. Hiemeyer: Financial Interests, Personal, Full or part-time Employment: Bayer AG. B.H. Childs: Financial Interests, Personal, Full or part-time Employment: Bayer HealthCare Pharmaceuticals, Inc. M.J. Matasar: Financial Interests, Personal, Research Grant: Bayer; Financial Interests, Personal, Other, Consultancy, honoraria: Bayer; Financial Interests, Personal, Other, Consultancy: Daiichi Sankyo; Financial Interests, Personal, Research Grant: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Consultancy, honoraria: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Other, Consultancy: Juno Therapeutics; Financial Interests, Personal, Other, Consultancy: Merck; Financial Interests, Personal, Research Grant: Rocket Medical; Financial Interests, Personal, Other, Consultancy: Rocket Medical; Financial Interests, Personal, Research Grant: Seattle Genetics; Financial Interests, Personal, Other, Consultancy, honoraria: Seattle Genetics; Financial Interests, Personal, Other, Consultancy, honoraria: Takeda; Financial Interests, Personal, Other, Consultancy: Teva; Financial Interests, Personal, Research Grant: GlaxoSmithKline; Financial Interests, Personal, Other, Honoraria: GlaxoSmithKline; Financial Interests, Personal, Research Grant: ImmunoVaccine Technologies; Financial Interests, Personal, Other, Honoraria: ImmunoVaccine Technologies; Financial Interests, Personal, Research Grant: Janssen; Financial Interests, Personal, Other, Honoraria: Janssen; Financial Interests, Personal, Research Grant: Pharmacyclics; Financial Interests, Personal, Other, Honoraria: Pharmacyclics. P.L. Zinzani: Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Gilead; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Incyte; Financial Interests, Personal, Other, Honoraria, speakers’ bureau involvement, consultancy: Janssen; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Kyowa Kirin; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Merck; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement, consultancy: MSD; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Roche; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Servier; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: Takeda; Financial Interests, Personal, Other, Honoraria, speakers’ bureau involvement: TG Therapeutics; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement, consultancy: Verastem; Financial Interests, Personal, Other, Honoraria, board of directors or advisory committee membership, speakers’ bureau involvement: ADC Therapeutics; Financial Interests, Personal, Other, Board of directors or advisory committee membership, speakers’ bureau involvement: Celgene; Financial Interests, Personal, Other, Board of directors or advisory committee membership, speakers’ bureau involvement: Celltrion; Financial Interests, Personal, Other, Board of directors or advisory committee membership, speakers’ bureau involvement: Immune Design; Financial Interests, Personal, Other, Board of directors or advisory committee membership, speakers’ bureau involvement: Janssen-Cilag; Financial Interests, Personal, Other, Board of directors or advisory committee membership, speakers’ bureau involvement: Portola; Financial Interests, Personal, Other, Board of directors or advisory committee membership, speakers’ bureau involvement: Sandoz; Financial Interests, Personal, Other, Consultancy: Sanofi. All other authors have declared no conflicts of interest.