Efficacy, safety, and determination of RP2D of ABBV-383, a BCMA bispecific antibody, in patients with relapsed/refractory multiple myeloma (RRMM).

person Cesar Rodriguez Valdes Mount Sinai, Division of Hematology/Oncology, Department of Internal Medicine, New York, NY info_outline Cesar Rodriguez Valdes, Peter M. Voorhees, Anita D'Souza, Alfred Chung, Sascha Tuchman, Hana Safah, John T. McKay, Katja C Weisel, Raphael Teipel, Neha Korde, Ravi Vij, Orlando Felix Bueno, Tanya Rosenberg, Rajvineeth Kumar Pothacamury, Akshanth Polepally, Aarif Ahsan, Xin (Shane) Li (Lee), Ziyi Jin, Chetasi Talati, Shaji Kumar

Authors person Cesar Rodriguez Valdes Mount Sinai, Division of Hematology/Oncology, Department of Internal Medicine, New York, NY info_outline Cesar Rodriguez Valdes, Peter M. Voorhees, Anita D'Souza, Alfred Chung, Sascha Tuchman, Hana Safah, John T. McKay, Katja C Weisel, Raphael Teipel, Neha Korde, Ravi Vij, Orlando Felix Bueno, Tanya Rosenberg, Rajvineeth Kumar Pothacamury, Akshanth Polepally, Aarif Ahsan, Xin (Shane) Li (Lee), Ziyi Jin, Chetasi Talati, Shaji Kumar Organizations Mount Sinai, Division of Hematology/Oncology, Department of Internal Medicine, New York, NY, Plasma Cell Disorders Section, Department of Hematologic Oncology & Blood Disorders, Levine Cancer Institute, Atrium Health, Wake Forest University School of Medicine, Charlotte, NC, Division of Hematology/Oncology, Department of Medicine, Froedtert & Medical College of Wisconsin Cancer Center, Milwaukee, WI, Division of Hematology/Oncology, Department of Medicine, University of California San Francisco, San Francisco, CA, Division of Hematology, The University of North Carolina at Chapel Hill, Chapel Hill, NC, Tulane Cancer Center, Tulane University Schoool of Medicine, New Orleans, LA, Wake Forest University School of Medicine, Winston-Salem, NC, Department of Oncology, Hematology and Bone Marrow Transplantation with Section of Pneumology, University Medical Center Hamburg-Eppendorf, Hamburg, Germany, Medizinische Klinik I, Universitätsklinikum Carl Gustav Carus Dresden, Dresden, Germany, Myeloma Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, Washington University School of Medicine, St Louis, MO, AbbVie Inc., North Chicago, IL, Division of Hematology, Mayo Clinic, Rochester, MN Abstract Disclosures Research Funding AbbVie Background: MM eventually becomes refractory to current treatments, and new therapeutic options with convenient dosing and improved safety are needed to enhance patient (pt) adherence, access, and outcomes. ABBV-383 is a distinctive next-generation BCMA x CD3 bispecific antibody composed of 2 high-affinity BCMA-binding domains, a low-affinity CD3-binding domain designed to reduce cytokine release syndrome (CRS) risk, and a silenced Fc tail for an extended half-life allowing convenient dosing. ABBV-383 monotherapy has shown promising activity in the ongoing first-in-human phase 1 trial in RRMM (Vij et al. Blood 2023;142[suppl 1]:3378). Here, safety and efficacy results are reported that support the RP2D of 60mg Q4W as the optimal therapeutic ABBV-383 monotherapy dose. Methods: This phase 1 open-label, dose-escalation/expansion trial (NCT03933735) enrolled pts with RRMM who received ≥3 prior lines of therapy with exposure to PI, IMiD, and anti-CD38 mAb. ABBV-383 regimens explored in the expansion phase included 60mg Q4W and 40 or 60mg Q3W. A modified dexamethasone premedication schedule and shortened CRS monitoring period were implemented in the 60mg Q4W cohort for cycle 1. IV ABBV-383 was administered as a flat dose with no step-up schedule. Treatment was continued until disease progression/unacceptable toxicity. Primary objectives were to assess safety, tolerability, PK, PD, and determine the RP2D. Efficacy evaluation was a secondary objective. TEAEs were assessed per CTCAE v5.0 and tumor response per IMWG 2016 criteria. Results: As of May 2023, 220 pts received ABBV-383 (median age: 68 yr [35–92]; median prior therapy lines: 5 [3‒23]). Median FU was 4.1 mo (0.8–5.2) at 60mg Q4W (n=21), 12.2 mo (1.3–34.4) at 40mg Q3W (n=55), and 24.2 mo (0.6–33.4) at 60mg Q3W (n=61). At 60mg Q4W, with the modified premedication regimen, CRS was reported in 43% of pts (38% G1, 5% G2), and ICANS in 5% of pts (G2). In Q3W cohorts, CRS was reported in 71% (40mg; 45% G1, 25% G2) and 70% (60mg; 51% G1, 18% G2, 2% G3) of pts. The incidence of G3/4 neutropenia, anemia, and thrombocytopenia was 14/24/10% at 60mg Q4W, 31/31/16% at 40mg Q3W, and 34/13/13% at 60mg Q3W. G3/4 infections occurred in 10/24/34% of pts at 60mg Q4W, 40mg and 60mg Q3W, respectively. ORR and ≥VGPR were 65/50% at 60mg Q4W, 64/53% at 40mg Q3W, and 60/52% at 60mg Q3W. Corresponding exposure-response (ER) analyses and correlative analyses further supported RP2D determination (separate abstract submissions). Conclusions: The optimal therapeutic dose of 60mg Q4W ABBV-383 monotherapy was selected on the basis of safety, efficacy, and ER analyses. The extended interval of Q4W, with a shortened CRS monitoring period in cycle 1 and no step-up dosing, will improve convenience and reduce the treatment burden for pts. ABBV-383 at 60mg Q4W will be investigated in the registrational phase 3 trial (NCT06158841) in RRMM. Clinical trial information: NCT03933735.

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