CC-122, a novel cereblon-modulating agent, in combination with obinutuzumab (GA101) in patients with relapsed and refractory (R/R) B-cell non-hodgkin lymphoma (NHL)

Background: Patients (pts) with NHL experiencing early relapse (ER) within two years of initial diagnosis and those double refractory (DR) to both rituximab and chemotherapy have particularly poor outcomes (Casulo et al JCO 2015; Gopal et al. NEJM 2014). Preliminary results from CC-122-NHL-001, the first study of CC-122, a novel cereblon-modulating agent, in combination with obinutuzumab (G), showed promising response rates in pts with R/R B-cell NHL (Michot et al Blood 2016). Herein, we report updated results for safety and efficacy from CC-122-NHL-001 (NCT02417285) with further 12 months follow up. Methods: CC-122 was given orally (5/7 d) for 28-d cycles in escalating doses plus a fixed dose of intravenous G 1000 mg on d2, 8, 15 of cycle 1 (c1) and d1 of c2–8. CC–122 active ingredient in capsule formulation (AIC) 1, 2, 3, and 4 mg and CC-122 formulated capsules (F6) 3 and 4 mg were evaluated in separate cohorts. Primary end points included safety and tolerability, NTD, and MTD. Response was assessed using the Cheson 2007 criteria every 2 cycles to c6, every 3 cycles to c12, and every 6 cycles thereafter. Results: As of September 1, 2017, 44 pts with R/R B-cell NHL were enrolled in the dose-escalation phase. Tumor types included 19 pts with DLBCL, 24 with FL, and 1 with MZL. Median age was 60 y (range, 26–81 y), 29 (66%) were men, and 33 (75%) had stage III/IV disease. Median number of prior anticancer therapies was 3 (range, 1– 11), and 18 pts (41%) had 1 prior ASCT; 2 pts had a dose-limiting toxicity (grade 4 neutropenia, n ¼ 1 [CC-122 AIC 3 mg]; grade 5 tumor flare, n ¼ 1 [CC-122 F6 4 mg]). The most common (15%) grade 3/4 TEAEs were neutropenia (52%) and thrombocytopenia (25%). ORR/CR rate in the total population was 68%/27% (DLBCL, 47%/11%; FL, 84%/42%). The mDOR was 19.4 mo (95% CI:7.9, NR). Subgroup analysis showed comparable mPFS and DOR for high-risk (ERþDR) and standard-risk FL pts (mPFS, 21.1 mo [2.9, NR] vs 16.2 mo [1.7, 16.2]; DOR, 19.3 mo [1.9, NR] vs NR). Conclusions: CC-122þG is well-tolerated, with promising response rates and durable remissions in R/R B-cell NHL. Subgroup analysis showed CC-122þG has similar efficacy in the high-risk and standard-risk FL population

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