-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

725 Part 1 Results of a Dose Finding Study of Belantamab Mafodotin (GSK2857916) in Combination with Pomalidomide (POM) and Dexamethasone (DEX) for the Treatment of Relapsed/Refractory Multiple Myeloma (RRMM)Clinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 653. Myeloma/Amyloidosis: Therapy, excluding Transplantation; Novel Approaches for Relapsed/Refractory Myeloma and Amyloidosis
Hematology Disease Topics & Pathways:
Adult, multiple myeloma, Biological, antibodies, Diseases, Therapies, Plasma Cell Disorders, Study Population, Lymphoid Malignancies, Clinically relevant
Monday, December 7, 2020: 1:45 PM

Suzanne Trudel, MD, MSC, FRCPC1, Arleigh McCurdy, MD, BSc2, Heather J Sutherland, MD, PhD3,4, Martha L Louzada, MD, MSc5, Christopher P. Venner, MD6, Darrell J White, MD7, Rami Kotb, MD8*, Hira S Mian, MD9, Fernando Camacho, PhD10*, Molei Fu10*, Engin Gul, BS, MBA11*, Donna E. Reece, MD10 and Ibraheem Othman, MD, MSc, PhD12

1Division of Medical Oncology and Hematology, Princess Margaret Cancer Centre, University of Toronto, Toronto, Canada
2Department of Medicine, Division of Hematology, The Ottawa Hospital, Ottawa, ON, Canada
3Leukemia/BMT Program of BC, BC Cancer, Vancouver, BC, Canada
4Vancouver General Hospital, Vancouver, BC, Canada
5London Health Sciences Centre, London, ON, Canada
6Cross Cancer Institute, University of Alberta, Edmonton, AB, Canada
7Nova Scotia Health Authority, Halifax, NS, Canada
8Cancer Care Manitoba, Winnipeg, MB, Canada
9Department of Oncology, McMaster University, Hamilton, ON, Canada
10Canadian Myeloma Research Group (formerly MCRN), Vaughan, ON, Canada
11Canadian Myeloma Research Group, Toronto, ON, Canada
12Allan Blair Cancer Centre, Regina, SK, CAN

Background: Belantamab mafodotin (Belamaf), a first-in-class immunoconjugate targeting B-cell maturation antigen (BMCA), showed clinically meaningful activity and a manageable safety profile in patients (pts) with RRMM. Pomalidomide (POM) is an immunomodulatory drug (IMiD), that auguments T-cell and natural killer cell-mediated immunity. The ability of IMiDS to enhance immune responses including antibody-dependent cellular cytotoxic (ADCC) forms the basis for combining belamaf with POM.

Methods: A phase 1, 2-part multicenter, dose-escalation study evaluated the maximum tolerated does (MTD), recommended phase 2 dose (RP2D), safety, tolerability and efficacy of belamaf in combination with POM and dexamethasone (DEX) (B-Pd) in pts with RRMM. Eligible pts had received > 2 prior lines of treatment, were exposed to lenalidomide (LEN) and a proteasome inhibitor (PI) and were refractory to their last line of therapy. POM was administered at 4 mg days 1-21, DEX 40 mg (20 mg age > 75 years) weekly in conjunction with IV belamaf SINGLE (1.95 or 2.5 mg/kg, day 1) or belamaf SPLIT (2.5 or 3.4 mg/kg, split equally on days 1 and 8) Q4W. In addition, the protocol allowed for exploration of alternative schedules at the 2.5 mg/kg dose, including a 2.5 mg/kg LOADING dose followed by 1.92 mg/kg Q4W from cycle 2 onwards and 2.5 mg/kg dosed Q8W or Q12W. Dose escalation was accomplished using a standard 3+3 dose escalation design. 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. To better inform the RP2D for the expansion cohort in Part 2, up to 12 pts could be enrolled at dose levels not exceeding the MTD.

Results: As of July 13, 2020, 35 pts were enrolled after providing informed consent and completed the 28-day dose limiting toxicity (DLT) observation period. Pts were enrolled at the following dose levels and schedules: 1.92 Single (n=12), 2.5 Single (n=7), 2.5 Loading (n=5), 2.5 Split (n=6), 3.4 Split (n=5). Median age was 64 years (range 36-78) and median number of prior regimens was 3 (range 2-5). Prior therapies included stem cell transplant (68.6%), PI (100%, 80% refractory), LEN (100%, 88.6% refractory) and daratumamb (DARA) (45.7%, 100% refractory). 71.4% were refractory to LEN and a PI and 37.1% were refractory to LEN, PI and DARA. Of 19 pts with available cytogenetics, 8 (42.1%) were high risk, defined as del17p13, t(4;14), t(14;16) or 1q gain. All patients experienced at least 1 AE. The most frequent treatment emergent AEs (TEAEs) reported in >30% across all cohorts were keratopathy/microcyst-like epithelial changes (MEC) (65.7%) that was associated with an objective decrease in visual acuity (VA; 51.4%) or blurred vision (40%), fatigue (48.6%), neutropenia (48.6%), thrombocytopenia (48.6%) and fever (31.4%). Grade (G) 3/4 TEAEs reported in > 10% of pts were keratopathy/MEC (40.0%), neutropenia (37.1%), thrombocytopenia (34.3%), decreased VA (22.9%), lung infection (11.4%), and dyspnea (11.4%). Serious AEs were reported in 16 (45.7%) pts. AEs leading to dose holds of belamaf per treatment cycle were more frequent in the 2.5 SINGLE compared to the 1.92 SINGLE dosing cohorts (57.9% vs 22.9%, respectively). Three DLTs were observed, all were ocular events, 1 occurring in the 2.5 SINGLE (G3 keratopathy) and 2 in the 3.4 SPLIT cohorts (1 with G3 decreased VA + G3 keratopathy, 1 with G4 decreased VA +G3 keratopathy). Thus, the MTD was established as 2.5 mg/kg SINGLE and 2.5 mg/kg SPLIT in combination with standard dosing of POM/DEX.

At a median follow up 6 months, 29 pts are evaluable for response. Across all cohorts, the ORR was 86.2% (6 PR, 15 VGPR and 4 sCR). The median number of cycles administered was 6 (range 1-20). To date, 8 pts discontinued treatment due to progressive disease (PD) (n=5), patient decision (n=2) and adverse event of G4 decreased VA (n=1); 27 pts are ongoing. The mPFS has not been reached in any of the treatment groups. Table 1 summarizes efficacy data per dosing cohort.

Conclusions: The results show promising efficacy. The TEAEs were acceptable and consistent with the known safety profiles for belamaf and POM. However, the high rate of dose holds at the 2.5 mg/kg dose has prompted exploration of alternative dosing schedules that are enrolling and will be presented. The RP2D selection is pending completion of the current cohorts.

Disclosures: Trudel: Takeda: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria; AstraZeneca: Honoraria; Pfizer: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; GSK: Consultancy, Honoraria, Research Funding; Genentech: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Research Funding. McCurdy: Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Sanofi: Honoraria; GSK: Consultancy, Honoraria. Sutherland: Amgen: Consultancy; Celgene: Consultancy; Takeda: Consultancy, Honoraria; Bristol Myers Squibb: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Louzada: Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria. Venner: Celgene, Amgen: Research Funding; Janssen, BMS/Celgene, Sanofi, Takeda, Amgen: Honoraria. White: Amgen: Honoraria; Celgene: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Karyopharm: Honoraria; Antengene: Honoraria; GSK: Honoraria; Takeda: Honoraria. Kotb: Merck: Honoraria, Research Funding; Karyopharm: Current equity holder in publicly-traded company; Celgene: Honoraria; Amgen: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Sanofi: Research Funding. Mian: Takeda: Consultancy, Honoraria; Sanofi: Consultancy; Janssen: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; Celgene: Consultancy. Camacho: Bausch-Health: Consultancy; Janssen: Consultancy; AbbVie: Consultancy. Reece: Otsuka: Research Funding; Celgene: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Merck: Research Funding; BMS: Research Funding; Millenium: Research Funding; Amgen: Consultancy, Honoraria; Karyopharm: Consultancy. Othman: Celgene: Honoraria; Janssen: Honoraria; Sanofi: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Roche: Honoraria.

OffLabel Disclosure: Use of pomalidomide and dexamethasone with belamantamab mafodotin

*signifies non-member of ASH