Talquetamab (tal) + daratumumab (dara) in patients (pts) with relapsed/refractory multiple myeloma (RRMM): Updated TRIMM-2 results.

person Bhagirathbhai R. Dholaria Vanderbilt University Medical Center, Nashville, TN info_outline Bhagirathbhai R. Dholaria, Katja Weisel, Maria-Victoria Mateos, Hartmut Goldschmidt, Thomas G. Martin, Daniel Morillo, Donna Ellen Reece, Paula Rodríguez-Otero, Manisha Bhutani, Anita D'Souza, Albert Oriol, Laura Rosiñol, Nizar J. Bahlis, Kalpana Bakshi, Lijuan Kang, Lien Vandenberk, Marie-Anne Damiette Smit, Ralph Wäsch, Niels W.C.J. van de Donk, Ajai Chari

Authors person Bhagirathbhai R. Dholaria Vanderbilt University Medical Center, Nashville, TN info_outline Bhagirathbhai R. Dholaria, Katja Weisel, Maria-Victoria Mateos, Hartmut Goldschmidt, Thomas G. Martin, Daniel Morillo, Donna Ellen Reece, Paula Rodríguez-Otero, Manisha Bhutani, Anita D'Souza, Albert Oriol, Laura Rosiñol, Nizar J. Bahlis, Kalpana Bakshi, Lijuan Kang, Lien Vandenberk, Marie-Anne Damiette Smit, Ralph Wäsch, Niels W.C.J. van de Donk, Ajai Chari Organizations Vanderbilt University Medical Center, Nashville, TN, University Medical Center of Hamburg-Eppendorf, Hamburg, Germany, University Hospital of Salamanca, Salamanca, Spain, Medizinische Klinik V, Universitätsklinikum Heidelberg and Nationales Centrum für Tumorerkrankungen, Heidelberg, Germany, Helen Diller Family Comprehensive Cancer Center, San Francisco Medical Center, University of California, San Francisco, CA, Hospital Universitario Fundación Jiménez Díaz, Madrid, Spain, Princess Margaret Cancer Centre, Toronto, ON, Canada, Clínica Universidad de Navarra, CIMA, CIBERONC, IDISNA, Pamplona, Spain, Levine Cancer Institute/Atrium Health, Charlotte, NC, Medical College of Wisconsin, Milwaukee, WI, Institut Català d’Oncologia and Institut Josep Carreras, Hospital Germans Trias i Pujol, Badalona, Spain, Hospital Clínic de Barcelona, IDIBAPS, Barcelona, Spain, Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada, Janssen Research & Development, Spring House, PA, Janssen Research & Development, Antwerp, Belgium, Janssen Biologics Europe, Leiden, Netherlands, Freiburg University Medical Center, Freiburg, Germany, Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands, Mount Sinai School of Medicine, New York, NY Abstract Disclosures Research Funding Pharmaceutical/Biotech Company Janssen Research & Development, LLC Background: Tal is a T-cell redirecting bispecific antibody (BsAb) targeting G protein–coupled receptor family C group 5 member D. Dara is an anti-CD38 mAb with direct on-tumor and immunomodulatory actions. Combining immunomodulatory effects of tal + dara may lead to synergistic efficacy. Initial TRIMM-2 (NCT04108195) results showed that SC tal RP2Ds, 0.4 mg/kg QW or 0.8 mg/kg Q2W, + SC dara had promising efficacy and increased CD38+/CD8+ T cells and proinflammatory cytokines. We report updated results with additional pts and longer follow-up. Methods: Pts had MM, ≥3 prior lines of therapy (LOT; including a proteasome inhibitor [PI] and immunomodulatory drug [IMiD]) or were double refractory to a PI and IMiD, and had not received anti-CD38 therapy in ≤90 d. Pts received tal RP2Ds with step-up dosing + dara 1800 mg per approved schedule. AEs were graded per CTCAE v5.0; cytokine release syndrome (CRS) and immune effector cell–associated neurotoxicity syndrome (ICANS) were graded per ASTCT guidelines. Responses were assessed per IMWG criteria. Results: As of Dec 12, 2022 (N = 65), median follow-up was 11.5 mo (range 1.0–27.3). Median age was 63 y (range 37–81); 18% of pts had high-risk cytogenetics; 25% had extramedullary plasmacytomas. Median prior LOT was 5 (range 2–16): 63% penta-drug exposed; 58% triple-class refractory. Prior treatments included anti-CD38 (88% [77% refractory]), anti-BCMA (54% [38%]), BsAb (25% [25%]), and anti-BCMA CAR-T (17% [2%]) therapy. All pts had ≥1 AE (grade [Gr] 3/4 78%), most commonly CRS (78%; all Gr 1/2), dysgeusia (75%), dry mouth (55%), anemia (52%), fatigue (45%), and skin exfoliation (45%). CRS had a median time to onset of 1 d after the most recent dose with median duration of 2 d. 63% of pts had infections (Gr 3/4 22%; Gr 5 3% [n = 2 pneumonia, possibly related to tal + dara]). 38% of pts had neutropenia (Gr 3/4 26%). 85% had postbaseline IgG < 500 mg/dL; of these, 32% received IVIg. ICANS occurred in 3 pts (5%; all Gr 1/2 and resolved in 1–2 d). ORR was 78% (66% ≥VGPR; 45% ≥CR) across RP2Ds (100% in anti-CD38 naïve pts), and responses deepened over time. In pts exposed/refractory to prior therapy, ORRs were 75%/76% for anti-CD38, 74%/64% for anti-BCMA, and 75%/75% for BsAb. Median time to first response was 1 mo (range 0.9–8.3); at 12 mo, 86% of responders (89% of pts with ≥CR) still had responses. At data cutoff, 84% of responders remain on therapy (83%/82% anti-CD38 exposed/refractory). mPFS was 19.4 mo; 12-mo PFS and OS rates were 76% and 93%, respectively. Conclusions: Steroid-sparing tal + dara showed deep and durable responses with promising mPFS in heavily pretreated pts with RRMM, including pts refractory to anti-CD38/BCMA and T-cell redirecting therapy, suggesting combined immunomodulatory actions can yield robust responses in pts with refractory disease. The safety profile was clinically manageable; no new signals were identified with longer follow-up.