EHA 2018 | Phase I study of the synergistic effects of CC-122 and obinutuzumab

On Friday 15th June an oral abstract session took place at the 23rd congress of the European Hematology Association (EHA). Abstract S104 was presented by Jean-Marie Michot, Institute Gustave Roussy, Villejuif, France, on the drug CC-122, which is a novel cereblon-modulating agent used in combination with obinutuzumab in patients with relapsed/refractory (R/R) non-Hodgkin lymphoma (NHL).

CC-122 targets Cereblon and induces degradation of Aiolos and Ikaros that has a dual effect. One is the tumoricidal effects of ISGs (IRF7 and OAS) and another effect is T- and NK-cell activation.

Study Overview
  • The initial part of the study was a dose escalation followed by dose expansion
  • The recommended dose for the dose expansion was 3 mg CC-122 + obinutuzumab divided into two cohorts of patients with follicular lymphoma (FL). The FL-1 cohort had R/R CD20+ disease and were lenalidomide-treated. The FL-2 cohort had R/R CD20+ disease and were lenalidomide-naïve
  • The primary endpoint of the study was to assess the safety and tolerability of CC-122 with obinutuzumab. To identify the non-tolerated dose, maximum tolerated dose (MTD), and the recommended phase II dose
  • The secondary endpoints included; preliminary efficacy, overall response rate (ORR) and progression-free survival (PFS)
Key Findings
  • The best ORR:
    • Diffuse large B-cell lymphoma (DLBCL) (n = 19) = 47%
    • FL + MZL (n = 30) = 77%
  • Median PFS:
    • DLBCL = 4.7 months (95% CI, 1.8–13.8)
    • FL + MZL = 16.6 months (95% CI, 5.4–not reached)
  • The most frequent Grade 3/4 adverse events were neutropenia (55%) and thrombocytopenia (22%)
  • 1 patient had a grade 5 tumor flare reaction/tumor lysis syndrome (dose 4 mg CC-122 + obinutuzumab)

The study found that the recommended dose of CC-122 for future clinical studies was 3 mg with obinutuzumab. This combination demonstrated a high response rate for patients with FL. Additionally, the adverse events during this study were manageable with no unexpected toxicities.


Michot JM. 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). Abstract S104. 23rd Congress of EHA, Stockholm, Sweden

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