Introduction: Teclistamab (tec) is the first approved B-cell maturation antigen (BCMA) × CD3 bispecific antibody (BsAb) for the treatment of patients (pts) with triple-class exposed relapsed/refractory multiple myeloma (RRMM), with weight-based dosing and the longest study follow-up of any BsAb in MM. Tec has demonstrated rapid, deep, and durable responses with a manageable safety profile in 3 clinical studies with registrational intent: the pivotal MajesTEC-1 cohort (NCT03145181/NCT04557098), the China cohort of MajesTEC-1, and the Japan phase 1/2 study (NCT04696809). Here, we present pooled data of 217 pts treated with tec at the recommended phase 2 dose (RP2D) in this globally representative population.

Methods: Pts had RRMM and received ≥3 prior lines of therapy (LOT), including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 monoclonal antibody. Pts received tec at the RP2D (1.5 mg/kg subcutaneous [SC] once weekly preceded by step-up dosing with the option to switch to less frequent dosing if responses were maintained); study population included 165 pts from the pivotal MajesTEC-1 cohort (enrolled Mar 2020-Aug 2021, 30.4-month [mo] median follow-up), 26 pts from the China cohort of MajesTEC-1 (enrolled Dec 2021-Sep 2022, 15.3-mo median follow-up), and 26 pts from phase 2 of the Japan study (enrolled Jul 2022-Mar 2023, 14.3-mo median follow-up). The primary endpoint was overall response rate (ORR). Key secondary endpoints were complete response or better (≥CR), very good partial response or better (≥VGPR), duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety graded per Common Terminology Criteria for Adverse Events v4.03.

Results: Of 217 pts, 53.9% were male, median age was 65 years (range, 33−84), median weight was 69.4 kg (range, 37.5-138.9), median prior LOT was 5 (range, 2-14), 29.0% had high-risk cytogenetics, and 18.9% had extramedullary disease. At 29.2 mo median follow-up, ORR (95% CI) was 66.4% (59.7-72.6), with 49.8% and 63.6% achieving ≥CR and ≥VGPR, respectively. Median DOR, PFS, and OS were 26.7, 15.1, and 26.3 mo, respectively. For pts with ≥CR (n=108), estimated 18-mo DOR, PFS, and OS were 76.3%, 77.7%, and 91.2%, respectively; medians were not reached. Eighty-eight pts (65, 10, and 13 in the pivotal, China, and Japan cohorts, respectively) switched to less frequent dosing. The most frequent treatment-emergent adverse events (TEAEs) were cytokine release syndrome, cytopenias, and infections, which are consistent with the known profile of anti-BCMA BsAbs. Infections occurred in 80.6% of pts (53.0% grade 3/4), including COVID-19 in 31.3% (22.6% grade 3/4). COVID-19 was the most common primary cause for grade 5 AEs (8.3%), all from the pivotal cohort that enrolled during the first peak of the COVID-19 pandemic. Discontinuations occurred in 9/217 (4.1%) pts due to TEAEs, with 5/9 due to infections.

In the 52 pts who were enrolled after the pivotal MajesTEC-1 cohort (China cohort and Japan study), baseline features were generally similar except for weight (median, 58.0 kg [range, 37.5-86.4]). At 14.9 mo median follow-up, ORR (95% CI) was 76.9% (63.2-87.5), with 61.5% and 76.9% achieving ≥CR and ≥VGPR, respectively. Estimated 18-mo DOR, PFS, and OS were 73.0%, 61.1%, and 74.9%, respectively; medians were not reached. For pts with ≥CR (n=32), estimated 18-mo DOR, PFS, and OS were 81.3%, 81.8%, and 93.1%, respectively; medians were not reached. Of pts with evidence of hypogammaglobulinemia, 91.3% (42/46) received ≥1 dose of intravenous or SC immunoglobulin (IVIg/SCIg) in this Asian cohort. There were no discontinuations due to infections; 1 pt had grade 5 pneumonia that occurred in the setting of COVID-19 in the China cohort.

Conclusions: In the largest clinical cohort to date treated with tec at the RP2D (N=217), with a median follow-up of 29.2 mo, tec consistently demonstrated deep and durable responses, including an ORR of 66.4%, ≥CR of 49.8%, and median DOR of 26.7 mo, with a manageable safety profile. Evolving evidence, awareness, and International Myeloma Working Group guidance on infection management strategies, such as IVIg/SCIg use with tec, were reflected in the more recent China and Japan cohorts, which translated into higher response rates, improved OS and PFS, and a lower frequency of fatal infections compared with the initial pivotal MajesTEC-1 cohort (n=165).

Disclosures

Martin:GSK, Pfizer, Roche: Honoraria; Janssen: Research Funding; Poseida: Research Funding; BMS: Research Funding; Sanofi: Research Funding. Mateos:AbbVie, Amgen, Bluebird bio, Celgene, GlaxoSmithKline, Janssen, Kite, Oncopeptides, Pfizer, Regeneron, Roche, Sanofi, Stemline, and Takeda: Honoraria. van de Donk:Merck: Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Roche: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Sanofi: 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; Cellectis: Research Funding; Novartis: Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Servier: Membership on an entity's Board of Directors or advisory committees; Kite Pharma: Consultancy, Membership on an entity's Board of Directors or advisory committees. Garfall:Abbvie, Bristol Myers Squibb, Regeneron, Smart Immune: Consultancy; CRISPR Therapeutics, Tmunity: Research Funding; GlaxoSmithKline: Honoraria; Johnson & Johnson: Honoraria, Research Funding; Legend Bio: Honoraria; Novartis: Consultancy, Research Funding. Iida:Alexion: Research Funding; AstraZeneca: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Research Funding; GlaxoSmithKlein: Consultancy, Research Funding; Otsuka: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Amgen: Research Funding; Sanofi: Consultancy, Honoraria, Research Funding; Takeda: Honoraria, Research Funding; Ono: Honoraria, Research Funding; Daiichi Sankyo: Research Funding; Shionogi: Research Funding; Chugai: Research Funding; Pfizer: Consultancy, Honoraria, Research Funding. Kuroda:Janssen Pharmaceutical, Takeda Pharmaceuticals, Bristol Myers Squibb, Sanofi, SymBio Pharmaceuticals, ONO PHARMACEUTICAL, AstraZeneca, ASAHI KASEI PHARMA, Amgen: Research Funding, Speakers Bureau. Nooka:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sebia: Honoraria, Membership on an entity's Board of Directors or advisory committees; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; ONK Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; Aduro Biotech: Research Funding; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; K36 Therapeutics: Honoraria, Membership on an entity's Board of Directors or advisory committees; AstraZeneca: 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, Research Funding; Arch Oncology: Research Funding; Cellectar Biosciences: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bristol-Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Cellectis: Research Funding; Genentech: Research Funding; Karyopharm: Research Funding; Kite Pharma: Research Funding; Merck: Research Funding. Sidana:Novartis: Research Funding; Legend: Consultancy; BiolineRx: Consultancy; Abbvie: Consultancy; Regeneron: Consultancy; Janssen: Consultancy, Research Funding; Oncopeptides: Consultancy; Kite, A Gilead company: Consultancy; BMS: Consultancy, Research Funding; Sanofi: Consultancy; Pfizer: Consultancy; Takeda: Consultancy. Chastain:Janssen: Current Employment, Current holder of stock options in a privately-held company. Doyle:Johnson and Johnson: Current Employment, Current equity holder in publicly-traded company. Nishikawa:Johnson & Johnson: Current Employment, Current holder of stock options in a privately-held company. Yamazaki:Janssen Research & Development, LLC: Current Employment, Current equity holder in publicly-traded company. Zhuo:Janssen: Current Employment, Current equity holder in publicly-traded company. Zhu:Johnson & Johnson: Current Employment, Current holder of stock options in a privately-held company.

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2024
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