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3331 Pooled Efficacy and Safety of Teclistamab in 217 Patients with Triple-Class Exposed Relapsed/Refractory Multiple Myeloma from 3 Registrational Clinical Studies

Program: Oral and Poster Abstracts
Session: 653. Multiple Myeloma: Clinical and Epidemiological: Poster II
Sunday, December 8, 2024, 6:00 PM-8:00 PM

Thomas G. Martin, MD1, María-Victoria Mateos, MD, PhD2, Niels W.C.J. van de Donk, MD, PhD3*, Zhen Cai4*, Weijun Fu5*, Alfred L Garfall6*, Shinsuke Iida, MD, PhD7, Yoshiaki Kuroda8*, Ting Niu, MD, PhD9, Ajay K. Nooka, MD, MPH10, Surbhi Sidana, MD11, Katherine Chastain, MD12, Margaret Doyle13, Kazuko Nishikawa14*, Yang Song15*, Hiroshi Yamazaki, MS14*, Jianmin Zhuo16*, Yan Zhu, PhD17*, Juan Du, MD, PhD18 and Tadao Ishida19

1University of California, San Francisco, San Francisco, CA
2University Hospital of Salamanca/IBSAL/CIC/CIBERONC, Salamanca, Spain
3Amsterdam University Medical Center, Vrije Universiteit Amsterdam, Amsterdam, Netherlands
4International College Zhejiang, University West District of Zijingang Campus, Zhejiang, China
5Shanghai Changzheng Hospital, Naval Medical University, Shanghai, China
6Abramson Cancer Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA
7Nagoya City University Institute of Medical and Pharmaceutical Sciences, Nagoya, Japan
8Hiroshima-Nishi Medical Center, National Hospital Organization, Hiroshima, Japan
9Department of Hematology, West China Hospital, Sichuan University, Chengdu, Sichuan, China
10Winship Cancer Institute of Emory University, Atlanta
11Stanford University School of Medicine, Stanford, CA
12Janssen Research & Development, Raritan, NJ
13Janssen Global Services, Dublin, Ireland
14Research and Development Division, Janssen Pharmaceutical K.K., Tokyo, Japan
15Janssen Research & Development, Beijing, China
16Janssen (China) Research & Development, Shanghai, China
17Janssen Asia Pacific Medical Affairs, Singapore, Singapore
18Department of Hematology, Myeloma & Lymphoma Center, Shanghai Changzheng Hospital, Shanghai, China
19Japanese Red Cross Medical Center, Tokyo, Japan

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.

*signifies non-member of ASH