Clinical Activity of CC-99282, a Novel, Oral Small Molecule Cereblon E3 Ligase Modulator (CELMoD) Agent, in Patients (Pts) with Relapsed or Refractory Non-Hodgkin Lymphoma (R/R NHL) - First Results from a Phase 1, Open-Label Study
CC-99282 is a novel, small molecule CELMoD ® agent that co-opts cereblon to induce targeted degradation of Ikaros/Aiolos, transcription factors critical for development of B-cell malignancies. Lopez-Girona et al. reported that in preclinical models, compared with lenalidomide and other immunomodulat...
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Veröffentlicht in: | Blood 2021-11, Vol.138 (Supplement 1), p.3574-3574 |
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Sprache: | eng |
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Zusammenfassung: | CC-99282 is a novel, small molecule CELMoD ® agent that co-opts cereblon to induce targeted degradation of Ikaros/Aiolos, transcription factors critical for development of B-cell malignancies. Lopez-Girona et al. reported that in preclinical models, compared with lenalidomide and other immunomodulatory agents, CC-99282 showed similar immunostimulatory effects and stronger antitumor activity along with robust distribution across multiple tissues. In addition, CC-99282 was shown to exhibit 10- to 100-fold enhanced antiproliferative and apoptotic activity in a range of diffuse large B-cell lymphoma (DLBCL) cell lines, independent of subtype or chemotherapy-resistant status (Lopez-Girona, et al. Hematol Oncol. 2021). Here, we present results from CC-99282-NHL-001, a phase 1, open-label, dose-finding, first-in-human study evaluating CC-99282 in pts with R/R NHL (NCT03930953).
This multicenter study consists of 2 parts, dose escalation of CC-99282 monotherapy (part A) and expansion with or without combination partners (part B). Part A includes pts with R/R DLBCL or follicular lymphoma (FL) who have progressed after ≥ 2 lines of therapy, including prior CELMoD agent and chimeric antigen receptor T cell therapy (CAR T), or pts with R/R DLBCL who received ≥ 1 lines of standard therapy and are unfit for transplant. Pts receive oral CC-99282 (0.2 mg, 0.4 mg, 0.6 mg, or 0.8 mg) once daily following 3 different intermittent dosing schedules of 28-day cycles, with ≥ 3 pts in each dosing cohort. Primary objectives are to determine the safety, tolerability, maximum tolerated dose (MTD), and/or the recommended phase 2 dose (RP2D); secondary objectives include pharmacokinetics (PK) and preliminary efficacy of CC-99282 monotherapy in pts with R/R NHL. The pharmacodynamics (PD) of CC-99282 in R/R NHL is an exploratory endpoint.
As of April 9, 2021, 35 eligible pts were treated in part A (30 DLBCL and 5 FL). Median age was 66 (range 35-81) years and 57% were male. Median number of prior anticancer therapies was 3 (range 1-8); 7 (20%) pts had received CAR T, 7 (20%) had received prior stem cell transplants, and 20 (57%) were refractory to last treatment.
Median treatment duration was 8 (range 4-72) weeks, and at time of analysis 8 (23%) pts were still on treatment and 22 (63%) had discontinued treatment because of progressive disease. Twenty-one (60%) pts had a treatment-emergent adverse event (TEAE) of grade 3/4 related to CC-99282, the most common being neutropenia (19 pts [5 |
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ISSN: | 0006-4971 1528-0020 |
DOI: | 10.1182/blood-2021-147333 |