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

On Friday 15^th June an oral abstract session took place at the 23^rd 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; tumoricidal effects of ISGs (IRF7 and OAS) and 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)

Safety

• 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.