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4562 Sea-BCMA Mono- and Combination Therapy in Patients with Relapsed/Refractory Multiple Myeloma: Updated Results of a Phase 1 Study (SGNBCMA-001)

Program: Oral and Poster Abstracts
Session: 653. Myeloma and Plasma Cell Dyscrasias: Prospective Therapeutic Trials: Poster III
Hematology Disease Topics & Pathways:
Research, clinical trials, Biological therapies, Antibody Therapy, non-Hodgkin lymphoma, Lymphomas, Clinical Research, Plasma Cell Disorders, Diseases, Therapies, Lymphoid Malignancies
Monday, December 12, 2022, 6:00 PM-8:00 PM

James E. Hoffman, MD1*, Brea Lipe, MD2, Jason Melear, MD3, Michaela Liedtke, MD4, Mark A. Schroeder, MD5, Ruben Niesvizky, MD6, Christopher Strouse, MD7, Christopher A. Yasenchak, MD8, Damian J. Green, MD9, Jeremy Sauer, PhD10*, Yinghui Wang, MS10*, Phoenix Ho, MD10 and Al-Ola Abdallah, MD11

1Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL
2Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY
3Texas Oncology, Austin, TX
4Stanford University Medical Center, Stanford, CA
5Siteman Cancer Center, Washington University School of Medicine, Saint Louis, MO
6Weill Cornell Medicine, New York, NY
7Holden Comprehensive Cancer Center, University of Iowa, Iowa City, IA
8Willamette Valley Cancer Institute and Research Center, Eugene, OR
9Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA
10Seagen Inc., Bothell, WA
11University of Kansas Medical Center, Kansas City, KS

Background

SEA-BCMA is an investigational, humanized, effector enhanced, nonfucosylated IgG1 monoclonal antibody directed to BCMA. SGNBCMA-001 (NCT03582033) is an ongoing phase 1, open-label, multicenter, dose-escalation/expansion study evaluating the safety, tolerability, and antitumor activity of SEA-BCMA in adults with relapsed/refractory multiple myeloma (R/R MM). Part A comprised monotherapy dose escalation (100–1600 mg flat dosing by intravenous infusion) and dose expansion at the highest tolerated dose; SEA‑BCMA 1600 mg once every 2 weeks (Q2W) was generally well-tolerated and showed initial antitumor activity with an overall response rate (ORR) of 14% (95% confidence interval [CI]: 2.9, 34.9; n=22; Hoffman 2021). Here, we evaluated intensive SEA-BCMA dosing (Part B) and the addition of dexamethasone (DEX; Part C) to further assess the safety, tolerability, and clinical activity.

Methods

Parts B and C enrolled patients (pts) who have received ≥3 prior lines of therapy for MM and are triple-class refractory. Responses are assessed per the 2016 International Myeloma Working Group criteria. These expansion cohorts are testing intensive dosing (Part B; weekly induction dosing of SEA-BCMA for 8 weeks is followed by Q2W maintenance dosing) and DEX combination therapy with either standard SEA-BCMA dosing (Part C1) or intensive SEA-BCMA dosing (Part C2; 800 mg [dose level -1] or 1600 mg [dose level 1]).

Results

As of 16 May 2022, a total of 73 pts received SEA-BCMA. Patient baseline characteristics are summarized in Table 1.

The most common non-hematologic, treatment-emergent adverse events (TEAEs) in Parts B (n=15), C1 (n=12), and C2 (n=8) were fatigue (33%, 50%, and 25%), back pain (20%, 17%, and 25%), pneumonia (7%, 25%, and 25%), and cough (20%, 8%, and 25%). The most common hematologic TEAE was anemia (42% in Part C1). The most common ≥Grade 3 TEAEs were anemia (33% in Part C1) and pneumonia (7%, 25%, and 0% for Parts B, C1, and C2, respectively).

Both intensive SEA-BCMA dosing (Part B) and the addition of DEX (Part C1) showed increased ORRs relative to Q2W monotherapy (Part A; Table 2). In Part B (n=15), the ORR was 27% (95% CI: 7.8, 55.1); median duration of response (DOR) was 6.5 months (95% CI: 1.8, -); 3 pts remain on treatment, including 2 responders. In Part C1 (n=12), the ORR was 17% (95% CI: 2.1, 48.4); the median DOR was not yet reached; 1 responding pt remains on treatment.

For the combination of the intensive SEA-BCMA dosing schedule and the addition of DEX (Part C2), the ORR across both SEA-BCMA dose levels (800 mg [n=3] and 1600 mg [n=5]) was 38% (n=8; 95% CI: 8.5, 75.5); median DOR was not yet reached; 2 responding pts remain on treatment.

The combined ORRs of both intensive dosing cohorts (Parts B + C2) relative to both standard dosing (Q2W) cohorts (Parts A [1600 mg SEA-BCMA] + C1) were 30% versus 15%, respectively (Table 2).

Conclusions

Updated results for SEA-BCMA continue to demonstrate a favorable safety profile and combination potential. Encouraging preliminary data suggest that both the intensive dosing schedule and combination with DEX may increase clinical activity over Q2W monotherapy. Part C2 and Part D (testing the combination of SEA-BCMA with pomalidomide and DEX in pts who have received ≥3 prior lines of therapy), are enrolling. Part C2 has been amended to allow pts with prior exposure to BCMA-directed therapy to enroll.

Disclosures: Hoffman: Seagen Inc.: Research Funding; Celgene: Honoraria; Bristol Myers Squibb: Honoraria. Lipe: Janssen: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Sanofi: Consultancy; GSK: Consultancy; Seagen Inc.: Research Funding; Amgen: Research Funding; Harpoon: Research Funding. Melear: Janssen: Speakers Bureau; AstraZeneca: Speakers Bureau; TG Therapeutics: Speakers Bureau. Liedtke: Seagen Inc.: Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Natera: Membership on an entity's Board of Directors or advisory committees; Kura Oncology: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees, Research Funding; GSK: Membership on an entity's Board of Directors or advisory committees; Adaptive: Membership on an entity's Board of Directors or advisory committees; Allogene: Research Funding; Alnylam: Membership on an entity's Board of Directors or advisory committees; Bristol Myers Squibb: Membership on an entity's Board of Directors or advisory committees, Research Funding; Caelum: Research Funding; Gilead: Research Funding; Takeda: Membership on an entity's Board of Directors or advisory committees. Schroeder: Celgene: Research Funding; Fortis: Research Funding; Seagen Inc.: Research Funding; Amgen: Research Funding; Cellect Inc: Research Funding; Genentech Inc: Research Funding; Incyte: Research Funding. Niesvizky: Takeda: Consultancy, Research Funding; Karyopharm: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; GlaxoSmithKline: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding. Yasenchak: Takeda: Research Funding; Seagen Inc.: Consultancy, Research Funding; Beigene: Speakers Bureau. Green: Seagen Inc.: Research Funding. Sauer: Seagen Inc.: Current Employment, Current equity holder in publicly-traded company. Wang: Seagen Inc.: Current Employment, Current equity holder in publicly-traded company. Ho: Seagen Inc.: Current Employment, Current equity holder in publicly-traded company.

*signifies non-member of ASH