Magrolimab in Combination with Rituximab + Chemotherapy in Patients with Relapsed or Refractory (R/R) Diffuse Large B-Cell Lymphoma (DLBCL)

Background Despite recent advances in therapy options, treatment outcomes remain limited in patients with R/R DLBCL. Magrolimab is a first-in-class monoclonal antibody that blocks CD47, a "don't eat me" signal overexpressed on tumor cells, resulting in macrophage-mediated phagocytosis. Magrolimab in combination with rituximab (M+R) demonstrated encouraging safety and efficacy in patients with R/R DLBCL. We report preliminary results from the phase 1b study of M+R + gemcitabine and oxaliplatin (M+R-GemOx) in R/R DLBCL (NCT02953509).

Methods Patients eligible for the M+R-GemOx phase 1b cohort had de novo or transformed R/R DLBCL and were ineligible for intensive chemotherapy or autologous stem cell transplant (ASCT) or had relapsed after ASCT. Patients must have received at least 1 prior line of therapy and no more than 3, including prior anti-CD20 therapy. Magrolimab was administered intravenously (IV) at 1 mg/kg at an initial priming dose on day (D) 1, followed by a weekly dose of either 30 mg/kg (n=26) or 45 mg/kg (n=7) (cycles 1 and 2) followed by every-2-week maintenance dose (cycles ≥3) with R-GemOx. Rituximab 375 mg/m² was administered IV weekly during the first cycle starting with D8, monthly on D1 (cycles 2-6), and every other cycle (cycle ≥8). Gem 1000 mg/m² and Ox 100 mg/m² were both administered IV D11 and D23 (cycle 1) and D2 and D15 (cycles 2-4); dosing was permitted beyond cycle 4, per investigator discretion, for a total of 8 doses. Primary endpoints included safety, tolerability, and objective response rate (ORR) per the Lugano criteria as assessed by investigator. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), and overall survival (OS).

Results As of February 28, 2022, 33 patients were treated with M+R-GemOx. The majority were male (63.6%) with an Eastern Cooperative Oncology Group performance status of 0 or 1 (94%) and a median age of 71.0 (range, 31-86) years. Patients had either de novo (n=26) or transformed (n=7) DLBCL; 1 patient had double hit lymphoma. Patients had received a median of 2 (range, 1-7) prior anticancer therapies; 39.4% of patients had disease that was refractory to rituximab, and 42.4% of patients had disease that was refractory to last therapy. Six patients (18.2%) received prior ASCT. The mean (range) numbers of infusions were 16.2 (1.0-48.0), 7.3 (1.0-17.0), 4.4 (1.0-8.0), and 4.4 (1.0-8.0) for M, R, Gem, and Ox, respectively. The most common treatment-emergent adverse events (TEAEs) of any grade were anemia (69.7%; grade ≥3, 60.6%), thrombocytopenia (45.5% grade ≥3, 42.4%), and neutropenia (18.2%; all grade ≥3). Most high-grade TEAEs occurred within the first 12 weeks of therapy. Treatment-related TEAEs leading to magrolimab discontinuation were observed in 6.1% of patients. After a median follow-up of 11.3 (range, 0.1-33.4) months, the ORR and complete response (CR) rate were 51.5% and 39.4%, respectively. Median DOR and time to response (TTR) were 18.0 months (95% CI, 4.7 months to not estimable) and 1.9 (range, 1.8-3.4) months, respectively. Additional efficacy outcomes are presented in Panel 1.

Conclusions The tolerable safety profile and promising efficacy of M+R-GemOx, with deep and durable responses and median OS not reached, in patients with R/R DLBCL compares favorably with current standard-of-care regimens. M+R-GemOx also has the potential added advantage of outpatient delivery. This study supports further evaluation of magrolimab combinations for patients with lymphoma.

Asch:Gilead Sciences: Research Funding. Collins:ADC Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BeiGene: Consultancy, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees; Gilead: Consultancy, Honoraria, Speakers Bureau; Incyte: Honoraria, Membership on an entity's Board of Directors or advisory committees; Novartis: Honoraria, Speakers Bureau; SecuraBio: Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants / expenses, Speakers Bureau; Roche: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants / expenses, Speakers Bureau. Flinn:CALIBR: Research Funding; CTI Biopharma: Research Funding; Fate Therapeutics: Research Funding; Epizyme: Research Funding; City of Hope National Medical Center: Research Funding; CALGB: Research Funding; Millenium Pharmaceuticals: Research Funding; TCR2 Therapeutics: Research Funding; Biopath: Research Funding; Tessa Therapeutics: Research Funding; 2seventy bio: Research Funding; Forty Seven: Research Funding; Constellation Pharmaceuticals: Research Funding; ArQule: Research Funding; Portola Pharmaceuticals: Research Funding; Vincerx Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees; Servier Pharmaceuticals: Consultancy; Seattle Genetics: Research Funding; Pharmacyclics: Consultancy, Research Funding; Nurix Therapeutics: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; MorphoSys: Consultancy, Research Funding; Iksuda Therapeutics: Consultancy; InnoCare Pharma: Consultancy, Research Funding; Hutchison MediPharma: Consultancy; Takeda: Consultancy; Agios: Research Funding; Kite Pharma: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; Gilead Sciences: Research Funding; Genmab: Consultancy; Genentech: Consultancy, Research Funding; Century Therapeutics: Consultancy; Triphase Research & Development Corp: Research Funding; Incyte: Research Funding; Loxo@Lilly: Research Funding; Infinity Pharmaceuticals: Research Funding; Pfizer: Research Funding; Merck: Research Funding; Myeloid Therapeutics: Research Funding; Trillium Therapeutics: Research Funding; Bristol Myers Squibb: Research Funding; Rhizen Pharmaceuticals: Research Funding; IGM Biosciences: Research Funding; Acerta Pharma: Research Funding; Verastem: Consultancy, Research Funding; Unum Therapeutics: Research Funding; Roche: Consultancy, Research Funding; Curis: Research Funding; Forma Therapeutics: Research Funding; TG Therapeutics: Consultancy, Research Funding; Xencor: Consultancy; Secura Bio: Consultancy; Celgene: Research Funding; BeiGene: Consultancy, Research Funding; AstraZeneca: Consultancy, Research Funding; Abbvie: Consultancy, Research Funding. Ghosh:Seagen, TG Therapeutics, AstraZeneca, Phamacyclics, Janssen, Bristol Myers Squibb, Gilead Sciences, Beigene, Incyte, Karyopharm, Roche/Genentech, Novartis, Loxo Oncology, Genmab, Adaptive Biotech, ADC Therapeutics: Consultancy; TG Therapeutics, Genentech/Roche, Bristol Myers Squibb, Gilead, Morphosys, AbbVie: Research Funding; Gilead, AstraZeneca, Bristol Myers Squibb, Phamacyclics, Janssen, Epizyme: Speakers Bureau. Keane:Roche: Honoraria; Astra Zeneca: Honoraria, Other: Support for attending meetings and/or travel; Beigene: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Merk: Membership on an entity's Board of Directors or advisory committees. Ku:Antengene: Consultancy; Genor BioPharma: Consultancy; Roche: Consultancy; St Vincent's Hospital: Current Employment. Mehta:Norvartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Kyowa Kirin: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Pharmacyclics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; AstraZeneca: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; TG Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Takeda: Research Funding; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; Roche-Genentech: Research Funding; Merck: Research Funding; Kite/Gilead: Consultancy, Research Funding; Juno pharmaceuticals/BMS: Consultancy, Research Funding; Innate pharmaceuticals: Research Funding; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau; I-MAB: Research Funding; fortyseven Inc./Gilead: Consultancy, Research Funding, Speakers Bureau; Celgene/BMS: Consultancy, Research Funding, Speakers Bureau; Affimed: Research Funding; BeiGen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Morphosys/Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Seattle Genetics: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding, Speakers Bureau. O'Hear:Gilead Sciences: Current Employment, Current holder of stock options in a privately-held company, Other: Travel Support; Roche: Current holder of stock options in a privately-held company. Ren:Gilead Sciences: Current Employment, Current holder of stock options in a privately-held company. Villa:Gilead Sciences Inc: Current Employment, Current holder of stock options in a privately-held company, Research Funding. Lal:Gilead Sciences: Current Employment. Smith:TGTX: Consultancy; Bayer: Consultancy; Genentech: Consultancy; Kite Pharma: Consultancy; ADC Therapeutics: Consultancy; Gilead: Consultancy; BMS: Consultancy; Morphosys: Consultancy; Adaptive: Consultancy; Janssen: Consultancy; Karyopharm: Consultancy; Celgene: Consultancy; Portola: Research Funding; Gamida Cell: Consultancy; Bantam: Consultancy; Karyopharm: Consultancy; Chair, Lymphoma Research Foundation SAB: Membership on an entity's Board of Directors or advisory committees. Advani:ADC Therapeutics, Cyteir, Daiichi Sankyo, Gilead, Merck, Regeneron, Roche, Seattle Genetics: Research Funding; ADC Therapeutics, BMS, Daiichi Sankyo, Epizyme, Gilead, Incyte, Merck, Roche, Sanofi: Consultancy.