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3248 Belantamab Mafodotin in Combination with Pomalidomide and Dexamethasone Demonstrates Durable Responses in Triple Class Exposed/Refractory Multiple Myeloma

Program: Oral and Poster Abstracts
Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster II
Hematology Disease Topics & Pathways:
Antibody Therapy, Biological therapies, Combination therapy, Therapies
Sunday, December 11, 2022, 6:00 PM-8:00 PM

Suzanne Trudel1, Arleigh McCurdy, MD, BSc2, Molei Fu, MSc3*, Heather J. Sutherland, MD, PhD, FRCPC4, Martha L Louzada, MD, MSc5, Michael P. Chu, MD6, Darrell J White, MD7, Hira S Mian, MD8, Rami Kotb, MD, FRCPC9, Ibraheem Othman, MD, MSc, PhD10, Moustafa Kardjadj, PhD11*, Engin Gul, BSc, MBA12* and Donna E. Reece, MD, FRCPC3

1Department of Medical Oncology and Hematology, Princess Margaret Cancer Center, Toronto, ON, Canada
2Department of Medicine, Division of Hematology, The Ottawa Hospital, Ottawa, ON, Canada
3Canadian Myeloma Research Group (CMRG), Vaughan, ON, Canada
4Division of Hematology, Vancouver General Hospital, Vancouver, BC, Canada
5University of Western Ontario, London Health Sciences Centre, London, ON, Canada
6Department of Oncology, Cross Cancer Institute, Edmonton, AB, Canada
7Dalhousie University and Queen Elizabeth II Health Sciences Centre, Halifax, NS, Canada
8Department of Oncology, McMaster University, Hamilton, ON, Canada
9Department of Medical Oncology and Hematology, CancerCare Manitoba, Winnipeg, MB, Canada
10Allan Blair Cancer Centre, Saskatchewan Cancer Agency, Regina, SK, Canada
11Canadian Myeloma Research Group, Toronto, ON, Canada
12Canadian Myeloma Research Group (CMRG), Concord, ON, Canada

Background: Belantamab mafodotin (belamaf) is a first-in-class antibody-drug conjugate (ADC) targeting B-cell maturation antigen (BCMA). Belamaf has shown clinically meaningful activity as a single agent in relapse/refractory multiple myeloma (RRMM). The Algonquin study demonstrated that the anti-myeloma activities of belamaf are significantly increased by the immunomodulatory drug pomalidomide (POM). The Algonquin study is a two part study designed to evaluate the safety and efficacy of different doses and schedules of belamaf in combination with POM and dexamethasone (DEX) (Bela-Pd) in patients (pts) with RRMM. Here we report updated safety and efficacy data for the subgroup of RRMM pts exposed or refractory to lenalidomide (LEN), a proteasome inhibitor (PI) and an anti-CD38 agent (triple class exposed).

Methods: Eligibility criteria included > 1 prior lines of treatment (LoT), LEN and PI exposure and refractoriness to the last LoT. POM was administered at 4 mg days 21/28 days, DEX 40 mg (20 mg age > 75 years) weekly in conjunction with IV belamaf administered as a SINGLE dose of 1.92 mg/kg Q4W or 2.5 mg/kg Q4W, Q8W or Q12W, or SPLIT equally (2.5 or 3.4 mg/kg) on days 1 and 8 Q4W. Responses were assessed by International Myeloma Working Group (IMWG) criteria and adverse events (AEs) were graded by CTCAE criteria except for corneal findings which were also graded by the pre-specified keratopathy and visual acuity (KVA) scale. In Part 1 up to 12 pts were enrolled in each cohort to inform the recommended part 2 dose (RP2D). In part 2, 23 patients will be enrolled to provide 35 patients (inclusive of the 12 treated at the RP2D of 2.5 mg/kg Q8W in Part 1) for overall response determination.

Results: At data cut-off (April 11, 2022), 54 triple class exposed pts had been enrolled in the following dose levels and schedules: 1.92 mg/kg Q4W (n=6), 2.5 mg/kg (SINGLE and SPLIT) Q4W (n=6), 2.5 mg/kg Q8W (n=26), 2.5 mg/kg Q12W (n=12), and 3.4 mg/kg SPLIT (n=4). The median age was 67.5 years (range 36-85) and median prior LoT was 3 (range 2-5). Prior therapies (exposed/refractory) included stem cell transplant (61.1%), PI (100%/79.6%), LEN (100%/92.6%), anti-CD38 (100%/100%) and 72.2% triple class refractory. The most frequent grade 1-2 AEs reported in all cohorts were keratopathy (an ophthalmologic finding) (68.6%), decreased best-corrected visual acuity (BCVA) (60.8%), fatigue (51.0%), thrombocytopenia (35.3%), and blurred vision (33.3%). Grade 3/4 AEs reported in >20% of pts across all cohorts, were keratopathy (54.9%), neutropenia (37.3%), thrombocytopenia (27.5%), and decreased BCVA (23.5%). Three patients discontinued treatment due to AEs (one G4 decreased visual acuity, one G3 elevated ALT, and one due to myelodysplastic syndrome) and three grade 5 AEs were observed (one from myeloma progression, one from lung infection, and one from myelodysplastic syndrome).

At data cut-off, 50/54 patients were evaluable for response. Across all cohorts the ORR was 86.0% (60.0% > VGPR). Responses by dosing cohort are summarized in Table 1. At a median follow-up of 5.7 months, the median PFS (n=49 at a data-cut of March 28, 2022) was 15.6 months (95% CI: 12.9, NYR; across all cohorts).

Conclusions: Patients who are triple class exposed/refractory remain challenging to treat and require therapies with novel mechanisms of action. In the recent LocoMMotion study, triple class exposed MM patients who prospectively received real-life standard of care (SOC) therapies demonstrated an overall response rate (ORR) of 29.8% and median PFS of 4.6 months. Thus, the combination of Bela-Pd represents an improvement over widely available SOC treatments for this poor prognosis patient population.

Disclosures: Trudel: Sanofi: Honoraria; Forus: Consultancy; Janssen: Honoraria, Research Funding; AstraZeneca: Honoraria; Karyopharm: Honoraria; Takeda: Honoraria; Genentech: Research Funding; Pfizer: Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Roche: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Research Funding. McCurdy: BMS: Honoraria, Research Funding; Sanofi: Honoraria; Janssen: Honoraria; Takeda: Honoraria; GSK: Honoraria; Forus: Honoraria; Amgen: Honoraria. Sutherland: Karyopharm: Research Funding; GSK: Research Funding; Janssen: Consultancy, Research Funding; Amgen: Consultancy; Celgene: Consultancy; Sanofi: Consultancy. Louzada: Celgene: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Janssen: Honoraria. Chu: Bristol Myers Squibb: Honoraria; Gilead: Honoraria; Sanofi: Honoraria; Janssen: Honoraria. White: Takeda: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; BMS/Celgene: Consultancy, Honoraria; Antengene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Karyopharm: Consultancy, Honoraria; Forus: Consultancy, Honoraria; GSK: Consultancy, Honoraria. Mian: Sanofi: Consultancy, Honoraria; Janssen: Consultancy, Honoraria, Research Funding; BMS: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria. Kotb: BMS: Honoraria; Sanofi: Honoraria, Research Funding; Amgen: Honoraria; Janssen: Honoraria; Pfizer: Honoraria; Merck: Honoraria, Research Funding; Karyopharm: Current equity holder in private company; Akcea: Honoraria; Takeda: Honoraria; Celgene: Honoraria. Reece: BMS: Research Funding; Sanofi: Honoraria; Amgen: Consultancy, Honoraria; Karyopharm: Consultancy; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Millenium: Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Otsuka: Research Funding; GSK: Honoraria.

*signifies non-member of ASH