Introduction: Talquetamab (tal) is an off-the-shelf, T-cell redirecting bispecific antibody (BsAb) targeting G protein-coupled receptor family C group 5 member D. Results from the phase 1/2 MonumenTAL-1 (NCT03399799/NCT04634552) trial showed overall response rates (ORRs) of >71%, which were durable, and a manageable safety profile with the recommended phase 2 doses (RP2Ds) of subcutaneous (SC) tal, 0.4 mg/kg weekly (QW) or 0.8 mg/kg every other week (Q2W), in patients (pts) with relapsed/refractory multiple myeloma. Data with tal also demonstrated preservation of B cells throughout treatment, contributing to relatively few severe infections. To date, there is a paucity of data describing pt outcomes after T-cell redirection therapies. Here, we report outcomes for pts who received subsequent antimyeloma therapies (SATs) after discontinuing tal in MonumenTAL-1, including pts who went on to receive subsequent T-cell redirection therapies.

Methods: Pts eligible for MonumenTAL-1 were intolerant to or progressed on established therapies (phase 1) or had ≥3 prior lines of therapy (LOT), including ≥1 proteasome inhibitor (PI), ≥1 immunomodulatory drug (IMiD), and ≥1 anti-CD38 monoclonal antibody (mAb) (phase 2). Pts received step-up doses and the QW or Q2W RP2Ds of SC tal until progressive disease (PD), unacceptable toxicity, withdrawal of consent, or death. Following tal discontinuation, SAT, start/end date of SAT, best response to SAT, and date of PD on SAT were recorded, if available. Data are pooled for the QW and Q2W RP2D cohorts. Response to SAT is based on investigator-reported assessment. Efficacy is presented for first SAT received post tal discontinuation.

Results: As of 17 Jan, 2023, 288 pts with no prior exposure to T-cell redirection therapies received tal at the RP2Ds (0.4 mg/kg QW [n=143] or 0.8 mg/kg Q2W [n=145]). Median prior LOT was 5. In the QW and Q2W cohorts, respectively, 74.1% and 69.0% were triple-class refractory, 29.4% and 23.4% were penta-drug refractory, and 15.4% and 11.0% had prior belantamab mafodotin exposure. Overall, 135 pts received ≥1 SAT post tal discontinuation: chemotherapy-based regimens (n=60 [44.4%]), a PI-, IMiD-, or other anti-neoplastic-containing regimen (n=40 [29.6%]), anti-CD38 mAb-containing regimens (n=36 [26.7%]), BsAbs (mostly monotherapy, n=23 [17.1%]: n=18 [13.3%] anti-B-cell maturation antigen [BCMA]; n=5 [3.7%] anti-Fc receptor-like protein 5 [FcRH5]), chimeric antigen receptor T-cell (CAR-T) therapy (n=20 [14.8%]; of whom n=18 [13.3%] were reported as receiving anti-BCMA-targeting CAR-T therapy), or anti-BCMA antibody-drug conjugates (n=13 [9.6%]). Time from tal discontinuation to the start of first SAT was generally similar across all drug classes (median, 1.1 months [range, 0.1-7.4]), including T-cell redirection therapies and bridging therapy in pts receiving CAR-T therapy: 1.5 months (range, 0.1-7.4) with CAR-T, 1.7 months (range, 1.0-3.5) with anti-BCMA BsAbs, and 1.0 month (range, 1.0-2.3) with anti-FcRH5 BsAbs. Best responses for each treatment class are shown in the Table. Pts had deep responses to CAR-T therapy as the first SAT post tal discontinuation with an ORR of 66.7% (8/12) (Table). ORR was 33.3% (2/6) in pts treated with anti-BCMA BsAbs as the first SAT post tal and 66.6% (2/3) with subsequent anti-FcRH5 BsAb therapy.

Conclusions: Pts from MonumenTAL-1 who discontinued tal were effectively treated with several classes of therapy. Subsequent treatment with T-cell redirection therapies appears feasible, with 25.0% of pts achieving a complete response or better with CAR-T therapy post tal. Further investigation in larger pt populations is warranted to better understand the sequencing of T-cell redirecting therapies after tal to optimize outcomes.

Sanchez:Janssen Pharmaceuticals: Consultancy, Honoraria. Krishnan:Adaptive Biotechnologies Corporation, Bristol-Myers Squibb Company, GlaxoSmithKline, Regeneron Pharmaceuticals Inc, Sanofi Genzyme: Other: Consulting Agreements; Amgen Inc, Bristol-Myers Squibb Company, Takeda Pharmaceuticals USA Inc: Other: Speakers Bureau; Bristol-Myers Squibb Company: Other: Stock Options/Ownership-Public Company; Janssen Biotech Inc: Other: Contracted Research; Sutro Biopharma: Other: Advisory Committee. Berdeja:Amgen: Research Funding; C4 Therapeutics: Research Funding; Acetylon: Research Funding; CARsgen: Research Funding; Incyte: Research Funding; GSK: Research Funding; Sanofi: Research Funding; Poseida: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; Celularity: Research Funding; Celgene: Consultancy, Research Funding; Karyopharm: Research Funding; Ichnos Sciences: Research Funding; Kite Pharma: Consultancy; EMD Serono: Research Funding; 2seventy bio: Consultancy, Research Funding; Bristol Myers Squibb: Consultancy, Research Funding; AbbVie: Research Funding; Fate Therapeutics: Research Funding; Genentech: Research Funding; Legend Biotech: Consultancy; Janssen: Consultancy, Research Funding, Speakers Bureau; Cartesian: Research Funding; Teva: Research Funding; Roche: Consultancy; Takeda: Consultancy, Research Funding; Lilly: Research Funding; Novartis: Research Funding. van de Donk:Abbvie: Other: Advisory Board; Pfizer: Other: Advisory Board; Bayer: Other: Advisory Board; Roche: Other: Advisory Board; Takeda: Other: Advisory Board; BMS: Other: Advisory Board, Research Funding; Cellectis: Research Funding; Novartis: Other: Advisory Board, Research Funding; Celgene: Other: Advisory Board, Research Funding; Amgen: Other: Advisory Board, Research Funding; Janssen Pharmaceuticals: Other: Advisory Board, Research Funding; Adaptive: Other: Advisory Board; Servier: Other: Advisory Board. Mateos:University of Salamanca/Gerencia Regional de Salud de Castilla y León: Current Employment; Takeda: Honoraria; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS-Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria; Abbvie: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Regeneron: Honoraria; Stemline: Honoraria, Membership on an entity's Board of Directors or advisory committees. Chari:Sanofi: Other: Advisory Board; Antengene: Consultancy; Janssen: Consultancy, Other: Advisory Board, Research Funding; Seattle Genetics: Other: Advisory Board, Research Funding; Karyopharm: Other: Advisory Board; Amgen: Consultancy, Other: Advisory Board, Research Funding; BMS: Consultancy, Other: Advisory Board, Research Funding; Millenium/Takeda: Consultancy, Research Funding; AbbVie: Other: Advisory Board; Secura Bio: Consultancy, Other: Advisory Board; Genentech: Other: Advisory Board; Shattuck Labs: Other: Advisory Board; Glaxo Smith Kline: Other: Advisory Board. Parekh:Karyopharm Therapeutics: Research Funding; Amgen: Research Funding; Celgene/BMS Corporation: Research Funding; Caribou Biosciences: Research Funding; Grail, LLC: Membership on an entity's Board of Directors or advisory committees. Mouhieddine:Legend Biotech: Consultancy. Jagannath:Caribou Biosciences: Consultancy; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees; DMC: Membership on an entity's Board of Directors or advisory committees; Regeneron: Consultancy; Takeda: Consultancy; Bristol Myers Squibb: Consultancy, Honoraria; Genmab: Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy; IMS: Membership on an entity's Board of Directors or advisory committees, Other: Support for attending meetings and/or travel; ASH: Membership on an entity's Board of Directors or advisory committees; SOHO: Membership on an entity's Board of Directors or advisory committees; Mount Sinai Hospital: Current Employment. Bahlis:Genentech/Roche: Honoraria; Abbvie: Consultancy, Honoraria, Other: member of steering committee; GSK: Consultancy, Other: member of steering committee; Forus: Consultancy, Honoraria; Takeda: Consultancy; BMS: Consultancy, Honoraria; Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Pfizer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: IRC member and chair, Research Funding. Touzeau:Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees. Oriol:Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Menarini: Membership on an entity's Board of Directors or advisory committees. San-Miguel:Amgen: Consultancy, Other: Advisory Board; Novartis: Other; MSD: Other: Advisory Board; Karyopharm: Other: Advisory Board; Haemalogix: Other: Advisory Board; Janssen-Cilag: Other: Advisory Board; Celgene: Other: Advisory Board; GSK: Other: Advisory Board; BMS: Other: Advisory Board; Takeda: Other: Advisory Board; Regeneron: Other: Advisory Board; Roche: Other: Advisory Board; Abbvie: Consultancy, Other: Advisory Board; Sanofi: Other: Advisory Board; SecuraBio: Other: Advisory Board. Rodriguez Otero:Oncopeptides: Membership on an entity's Board of Directors or advisory committees; Regeneron: Other: Honoraria for lectures; Pfizer: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Travel grants; Amgen: Other: Honoraria for lectures; GlaxoSmithKline: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Sanofi: Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Bristol Myers Squibb: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; Janssen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Honoraria for lectures; AbbVie: Consultancy, Membership on an entity's Board of Directors or advisory committees; Roche: Consultancy. Minnema:UMC Utrecht Cancer Center: Current Employment; Beigene: Research Funding, Speakers Bureau; CDR life: Consultancy; GSK: Consultancy; Janssen Cilag: Consultancy, Honoraria, Speakers Bureau. Campagna:Janssen: Current Employment, Current equity holder in publicly-traded company, Current holder of stock options in a privately-held company. Masterson:Janssen R&D: Current Employment, Current equity holder in private company. Hilder:Janssen: Current Employment, Current equity holder in private company. Tolbert:Janssen: Current Employment. Renaud:Johnson & Johnson: Current Employment, Current equity holder in private company, Current holder of stock options in a privately-held company. Gray:Janssen: Current Employment, Current equity holder in publicly-traded company. Smit:Janssen Biologics: Current Employment, Current equity holder in publicly-traded company. Heuck:Janssen: Current Employment, Current equity holder in private company. Rasche:Skyline Dx: Research Funding; BMS: Consultancy, Honoraria, Research Funding; Roche: Honoraria; Pfizer: Consultancy, Honoraria; Amgen: Consultancy; GSK: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Sanofi: Consultancy, Honoraria.

The abstract describes outcomes on subsequent therapies following discontinuation of talquetamab in the MonumenTAL-1 trial. The subsequent therapies received were per investigator choice and therefore included some investigational therapies not currently approved by regulatory authorities.

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2023
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