THREE PHASE 1/2, OPEN‐LABEL STUDIES OF CEREBLON E3 LIGASE MODULATOR (CELMOD)‐BASED REGIMENS IN NEWLY DIAGNOSED (ND) OR RELAPSED/REFRACTORY (R/R) NON‐HODGKIN LYMPHOMA (NHL) (2021)

Introduction: Lenalidomide (LEN)-based therapies have shown activity in NHL. These include LEN + anti-CD20 agent (rituximab or obinutuzumab) in follicular lymphoma (Morschhauser et al. N Engl J Med 2018; Morschhauser et al. Lancet Haematol 2019) and in R/R NHL (Wang et al. Leukemia 2013), as well as LEN + tafasitamab in R/R diffuse large B-cell lymphoma (DLBCL; Salles et al. Lancet Oncol 2020). Additionally, LEN + R-CHOP demonstrated significantly improved progression-free survival (PFS) versus R-CHOP in ND DLBCL (Nowakowski, Hong et al. J Clin Oncol 2021), and a positive trend in PFS in ABC subtype of ND DLBCL (Nowakowski, Chiappella et al. J Clin Oncol 2021). Early results also showed clinical activity of LEN + polatuzumab vedotin/obinutuzumab in R/R follicular lymphoma (Diefenbach et al. ASH 2019). Iberdomide (IBER; CC-220) and CC-99282 are novel oral CELMoDs that induce degradation of Ikaros/Aiolos, resulting in immunomodulatory and antitumor effects. IBER has 20x higher cereblon-binding affinity than LEN, leading to significantly faster degradation of target substrates (Matyskiela et al. J Med Chem 2018), and is active in NHL cell lines. CC-99282 displays efficacy in DLBCL cell lines independent of cell of origin. Thus, the use of CELMoDs may provide more effective therapies for ND and R/R NHL. Here we describe 3 dose-finding and safety studies (1 for NHL, 2 for aggressive B-cell lymphoma [a-BCL]) that will assess CELMoDs in combination with anti-CD20 agents, R-CHOP, or other agents in NHL. EA – previously submitted to ASCO 2021. The research was funded by: Bristol Myers Squibb Keywords: Aggressive B-cell non-Hodgkin lymphoma, Indolentnon-Hodgkin lymphoma, OngoingTrials Conflicts of interests pertinent to the abstract F. Morschhauser Consultant or advisory role: Roche, Genentech, Servier Other remuneration: Speakers' bureau: Roche, Gilead, Janssen. Board of directors or advisory committee: Roche, Gilead, Abbvie, Celgene, Epizyme G. Cartron Consultant or advisory role: Roche, Celgene Honoraria: Jansen, Sanofi, Novartis, Gilead, Roche, Celgene V. Kesanakurthy Employment or leadership position: Bristol Myers Squibb A. Gkasiamis Employment or leadership position: Bristol Myers Squibb P. Patah Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb R. Delarue Employment or leadership position: Celgene, a Bristol Myers Squibb company Stock ownership: Bristol Myers Squibb T. Wang Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb, Vir Biotechnology J. Li Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb Educational grants: Bristol Myers Squibb D. Xian Employment or leadership position: Bristol Myers Squibb C. P. Fox Consultant or advisory role: Abbvie, AstraZeneca, Atarabio, Bristol Myers Squibb/Celgene, Gilead, Janssen, Incyte, Roche, Takeda Honoraria: Abbvie, Atarabio, Bristol Myers Squibb/Celgene, Janssen, Incyte, Roche, Takeda Research funding: Abbvie, Gilead, Roche, Takeda Educational grants: Abbvie, Bristol Myers Squibb/Celgene, Janssen, Roche, Takeda P. Martin Consultant or advisory role: ADCT, AstraZeneca, Bayer, BeiGene, Bristol Myers Squibb, Cellectar, Epizyme, Gilead, Incyte, Janssen, Karyopharm, Merck, Regeneron, Takeda, Teneobio, Verastem