Golcadomide (GOLCA) ± Rituximab (RTX) Demonstrates Durable Efficacy and Is Well Tolerated in Patients (pts) with Relapsed/Refractory Follicular Lymphoma (R/R FL): Updated Results from the Phase 1/2 CC-99282-NHL-001 Study

Introduction:

GOLCA is a potential first-in-class CELMoD^TM agent for the treatment of lymphoma, purposefully designed to target the proteins Ikaros/Aiolos to produce dual immunomodulatory and anti-tumor activity, with preferential distribution to lymphoid organs. Pharmacodynamic data in pts with R/R FL show that, combined with RTX, the immunomodulatory effects of GOLCA are significantly increased (Chavez et al, EHA 2024, #1132). GOLCA as monotherapy (mono) and + RTX has been shown to be well-tolerated and effective in pts with R/R DLBCL (Chavez et al, ASH 2023, #4496) and R/R FL (Chavez et al, EHA 2024, #1132). Here, we report 30 mo follow up of pts with R/R FL who received GOLCA mono, and updated safety/efficacy of GOLCA + RTX from the ongoing Phase 1/2 CC-99282-NHL-001 study (NCT03930953).

Methods:

Pts with R/R FL with ≥ 2 prior lines of therapy (L) received GOLCA mono at different dosing schedules during part A (dose exploration) and GOLCA ± RTX at 0.2 mg or 0.4 mg days (d) 1-14 every 28 d (q28d) in part B (dose expansion). Total treatment duration with GOLCA was up to 2 years or until progressive disease or unacceptable toxicity, whichever occurred first. The efficacy-evaluable population consisted of pts completing ≥ 1 cycle of GOLCA and having baseline tumor assessment and ≥ 1 post-baseline tumor assessment or clinical progression or disease-related death.

Results:

As of May 31, 2024, 63 pts with R/R FL have enrolled: GOLCA mono (n = 19) at various dosing schedules and GOLCA + RTX at 0.2 mg (n = 22) or 0.4 mg (n = 22) on d1-14 q28d schedule. The median time from diagnosis to first dose of GOLCA was 68 mo (range, 23-136) and 59 mo (range, 15-309) in GOLCA mono and + RTX cohorts, respectively. The median number of prior therapies received was 4 (range, 2-11), and 3 (range, 1-12) in GOLCA mono and + RTX cohorts, respectively. In the GOLCA mono and + RTX cohorts, 9/19 (47%) and 13/43 (30%) pts had received prior lenalidomide (len)-based therapy, with 5/9 and 7/13 having len-refractory disease, respectively. In the GOLCA + RTX cohort, 10/43 (23%) had prior CAR T cell therapy and 6/43 (14%) had prior anti-CD20xCD3 bispecific antibody with or without CAR T cell therapy.

In the GOLCA + RTX-treated safety population (n = 43), the incidence of treatment emergent adverse events (TEAEs) was similar across 0.2 and 0.4 mg dose levels (DL). The most frequent grade (G) 3+ TEAEs were neutropenia (44%) and anemia (12%). The incidence of febrile neutropenia was 7%. Serious adverse events occurred in 30% of pts, with febrile neutropenia and pneumonia being the most common, in 2 pts (5%) each, as well as pulmonary embolism in 1 pt. Neutropenia led to GOLCA dose interruption in 4 pts (9%) and dose reduction in 1 pt (2%). No pts discontinued treatment because of GOLCA-related TEAEs. Non-hematological TEAEs (e.g., GI toxicity, rash, fatigue) were all low-grade (except 1 pt with G3 fatigue). There were no new safety signals identified for GOLCA mono (part A) at the 30-mo follow up period.

In the efficacy-evaluable population, at a median follow up of 6 mo (range 3-18), the ORR and CRR in the GOLCA + RTX cohort (n = 29) were 57% and 29% at 0.2 mg dose (n = 14) and 93% and 67% at 0.4 mg dose (n = 15), respectively. The median time to response was 2 mo (first response assessment). At the 0.4 mg DL of GOLCA + RTX, consistent responses were seen in pts at 2L/3L and 4L+, including in those with prior exposure to len-based therapies and/or T-cell-redirecting therapy. At the 0.4 mg DL, 12/14 (86%) pts remained in response at the time of data cut-off. In pts receiving GOLCA mono across different dose schedules in part A (n = 12), ORR and CRR were 67% and 42%, respectively. Responses were durable, with median DOR of 22 mo (range, 2-51) at a median follow up of 30 mo. 33% of pts (4/12) have completed 2 yrs of protocol defined GOLCA treatment and remain in response at the 1 yr post-treatment follow-up period, without requiring any intervening treatment.

Conclusions:

GOLCA 0.4 mg + RTX was well tolerated and highly active in heavily pre-treated pts with R/R FL, including those with prior exposure to len-based therapies and/or T-cell-redirecting therapies. Treatment with fixed-duration GOLCA mono led to durable responses including a subset of pts remaining treatment free, without progression at extended follow up. These data further support development of GOLCA + RTX as a fixed-duration, chemotherapy-free, outpatient treatment option in pts with R/R FL, and also pts with newly diagnosed advanced stage FL (NCT06425302).

Chavez:Merck: Research Funding; Lilly: Honoraria, Speakers Bureau; Janssen: Honoraria; Cellectis: Consultancy; Abbvie: Consultancy; GenMab: Consultancy, Research Funding; Allogene: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy, Honoraria, Speakers Bureau; ADC Therapeutics: Consultancy; Novartis: Consultancy; Kite, a Gilead Company: Consultancy. Perini:BMS, Roche, Abbvie, AsstaZeneca, Beigene: Speakers Bureau. Nastoupil:Denovo Biopharma: Honoraria; Daiichi Sankyo: Honoraria, Research Funding; BMS: Honoraria, Research Funding; Caribou Biosciences: Honoraria, Research Funding; AbbVie: Honoraria; ADC Therapeutics: Honoraria; Genentech: Honoraria, Research Funding; Genmab: Honoraria, Research Funding; Gilead Sciences/Kite Pharma: Honoraria, Research Funding; Incyte Corporation: Honoraria; Janssen: Honoraria, Research Funding; Merck: Honoraria, Research Funding; Novartis: Honoraria, Research Funding; Regeneron: Consultancy, Honoraria; Takeda: Consultancy, Honoraria, Research Funding; Abbvie, BMS, Caribou Biosciences, Genentech, Genmab, Gilead/Kite, Janssen, Incyte, Ipsen, Merck, Novartis, Regeneron, Takeda: Consultancy; BMS, Caribou Biosciences, Daiichi Sankyo, Genentech, Genmab, Gilead/Kite, Janssen, Incyte, Ipsen, Merck, Novartis, Takeda: Research Funding; Abbvie, BMS, Caribou Biosciences, Daiichi Sankyo, Genentech, Genmab, Gilead/Kite, Janssen, Incyte, Ipsen, Novartis, Takeda: Honoraria. Joergensen:Sobi: Consultancy; Caribou: Consultancy; Incyte: Consultancy; Kite/Gilead: Consultancy; Roche: Consultancy; Abbvie: Consultancy; Novo Nordisk: Current holder of stock options in a privately-held company. Bories:Abbvie, BMS-Celgene, Kite-Gilead, Novartis, Servier: Honoraria. Zinzani:CELLTRION, GILEAD, JANSSEN-CILAG, BMS, SERVIER, ASTRAZENECA, TAKEDA, ROCHE, KYOWA KIRIN, Incyte, Beigene: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; SECURA BIO, ADC Therap, Sandoz: Membership on an entity's Board of Directors or advisory committees; MSD, EUSAPHARMA, NOVARTIS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Munoz:Seattle Genetics: Consultancy, Research Funding; Alexion: Consultancy; Fosunkite: Consultancy; Karyopharm: Consultancy; Aurobindo: Consultancy; Verastem: Consultancy, Research Funding; Genzyme: Consultancy; Genentech/Roche: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Epizyme: Consultancy; Morphosys/Incyte: Consultancy, Research Funding; MEI: Consultancy; TG Therapeutics: Consultancy; AstraZeneca: Consultancy; Eli Lilly: Consultancy; Bayer: Consultancy, Research Funding; Portola: Research Funding; Merck: Research Funding; Targeted Oncology, OncView, Curio, Genzyme, and Physicians' Education Resource.: Honoraria; Celgene/Bristol Myers Squibb: Consultancy, Research Funding; Pfizer: Consultancy; Janssen: Consultancy, Research Funding; Beigene: Consultancy, Research Funding; Gilead/Kite: Consultancy, Research Funding; Pharmacyclics/Abbvie, Bayer, Gilead/Kite, Beigene, Pfizer, Janssen, Celgene/Bristol Myers Squibb, Kyowa, Alexion, Fosunkite, Seattle Genetics, Karyopharm, Aurobindo, Verastem, Genmab, Genzyme, Genentech/Roche, ADC Therapeutics, Epizyme, Beigene, Novartis,: Consultancy; Novartis: Consultancy, Research Funding; Curio: Honoraria; Physicians' Education Resource: Honoraria; OncView: Honoraria; Alexion: Consultancy; Targeted Oncology: Honoraria; Pharmacyclics/Abbvie: Consultancy, Honoraria, Research Funding; Bayer: Consultancy, Research Funding; Genmab: Consultancy; Kyowa: Consultancy; BeiGene: Consultancy; Bayer, Gilead/Kite, Celgene, Merck, Portola, Incyte, Genentech, Pharmacyclics, Seattle Genetics, Janssen, Millennium, Novartis, Beigene.: Research Funding. Morillo Giles:Roche, TAKEDA, GSK: Honoraria. Carpio:Janssen: Honoraria; Gilead: Honoraria; Novartis: Honoraria; Bristol Myers Squibb: Consultancy; Takeda: Consultancy, Honoraria; Regeneron Pharmaceuticals, Inc.: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Honoraria. Costa:Eli Lilly and Company, Knight Therapeutics: Speakers Bureau; Beigene, Roche, Regeneron: Research Funding; Johnson & Johnson, AbbVie, AstraZeneca: Research Funding, Speakers Bureau. Kim:Kyowa-Kirin: Research Funding; Boryong: Research Funding; Donga: Research Funding; Sanofi: Research Funding; F. Hoffmann-La Roche Ltd: Research Funding; BeiGene: Research Funding. Rao:Bristol Myers Squibb: Current Employment. de Moucheron:Bristol Myers Squibb: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Gang:Bristol Myers Squibb: Current Employment. Guarinos:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company. Sudhindra:Bristol Myers Squibb: Current Employment, Current holder of stock options in a privately-held company. Pourdehnad:Bristol Myers Squibb: Current Employment, Current equity holder in publicly-traded company.