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3018 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

Program: Oral and Poster Abstracts
Session: 623. Mantle Cell, Follicular, Waldenstrom’s, and Other Indolent B Cell Lymphomas: Clinical and Epidemiological: Poster II
Hematology Disease Topics & Pathways:
Clinical trials, Research, Combination therapy, Adult, Non-Hodgkin lymphoma, Lymphomas, Clinical Research, Diseases, Indolent lymphoma, Immunotherapy, Biological therapies, Treatment Considerations, Lymphoid Malignancies, Study Population, Human
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Julio C. Chavez, MD1, Guilherme Fleury Perini, MD2, Loretta Nastoupil3*, Judit Mészáros Joergensen, MD, PhD4*, Pierre Bories5*, Bijou Fontanet, MD6*, Pier Luigi Zinzani, MD7, Javier Munoz, MD8*, Daniel Morillo Giles, MD9*, Cecilia Carpio10*, Abel Costa, MD11*, Won Seog Kim, MD12*, Parth Rao, MD13*, Bérengère de Moucheron, PharmD14*, Yang Gang, PhD15*, Carla Guarinos14*, Akshay Sudhindra, MD13, Michael Pourdehnad, MD16 and Jean-Marie Michot, MD17*

1Department of Malignant Hematology, Moffitt Cancer Center, Tampa, FL
2Department of Medical Oncology, Hospital Israelita Albert Einstein, São Paulo, Brazil
3Department of Lymphoma & Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX
4Department of Hematology, Aarhus University Hospital, Aarhus, Denmark
5Early Phase Unit, University Cancer Institute Toulouse Oncopole, Toulouse, France
6Institut Bergonié, Bordeaux, France
7Institute of Hematology Seràgnoli, University of Bologna, Bologna, Italy
8Mayo Clinic, Phoenix, AZ
9START Madrid-FJD Early Phase Unit, Fundación Jiménez Díaz University Hospital, Madrid, Spain
10Department of Hematology, Vall d'Hebron Institute of Oncology (VHIO), University Hospital Vall d'Hebron, Autonomous University of Barcelona (UAB), Barcelona, Spain
11Department of Hematology, D'Or Institute for Research and Education, São Paulo, Brazil
12Samsung Medical Center, Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Seoul, Korea, Republic of (South)
13Late Clinical Development, Hematology/Oncology and Cell Therapy, Bristol Myers Squibb, Madison, NJ
14Center for Innovation and Translational Research Europe (CITRE), Bristol Myers Squibb, Seville, Spain
15Global Biometrics & Data Sciences, Bristol Myers Squibb, Madison, NJ
16Early Clinical Development, Hematology/Oncology and Cell Therapy, Bristol Myers Squibb, San Francisco, CA
17Département d'Innovation Thérapeutique et d'Essais Précoces (DITEP), Gustave Roussy Institute of Cancer, Villejuif, France

Introduction:

GOLCA is a potential first-in-class CELMoDTM 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).

Disclosures: 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.

*signifies non-member of ASH