Lisocabtagene Maraleucel (Liso-Cel) in R/R MCL: Primary Analysis Results From the MCL Cohort of the Single-Arm, Multicenter, Phase I Seamless Design TRANSCEND NHL 001 Study

Introduction: Patients (pts) with R/R MCL after ≥2 prior lines of therapy, including Bruton tyrosine kinase inhibitor (BTKi), have a poor prognosis. Liso-cel is an autologous, CD19-directed, CAR T cell product administered at equal target doses of CD8+ and CD4+ CAR+ T cells. The phase 1, seamless design, dose-finding TRANSCEND NHL 001 study (NCT02631044) evaluated liso-cel in pts with R/R NHL. Here we report primary analysis results from the MCL cohort. Methods: Eligible pts had PET-positive R/R MCL after ≥2 lines of prior therapy, including a BTKi, alkylating agent, and CD20-targeted agent. Pts received liso-cel at a target dose level (DL) of 50 (DL1) or 100 × 106 CAR+ T cells (DL2) after lymphodepleting chemotherapy (LDC). Bridging therapy was allowed. Primary endpoints were treatment-emergent AEs (TEAEs) and ORR by IRC (Lugano 2014 criteria); secondary endpoints included CR rate (key), DOR, PFS, and OS. Primary (null hypothesis [H0]: ORR ≤40%) and key secondary (H0: CR rate ≤18%) efficacy hypothesis testing was hierarchical and based on the primary analysis set (PAS) of pts treated at DL2 with PET-positive disease per IRC at baseline (before LDC, after bridging therapy). The safety set included all pts who received liso-cel (DL1 + DL2). The efficacy set included all pts in the safety set who had PET-positive disease per IRC at baseline (DL1 + DL2). Results: At data cutoff (01/19/2023), of 104 leukapheresed pts, 88 received liso-cel (safety set; DL1, n = 6; DL2, n = 82). Median (range) age was 68.5 y (36–86), median (range) prior systemic lines of therapy was 3 (1–11), 69% had refractory disease, 53% were BTKi refractory, 33% had prior HSCT, 75% had Ki67 ≥30%, 31% had blastoid morphology, 23% had TP53 mutations, and 8% had active CNS disease. Median (range) on-study follow-up was 16.1 mo (0.4–60.5). The primary and key secondary endpoints were met based on the PAS (n = 74; ORR, 86.5% [95% CI, 76.5–93.3], P < 0.0001; CR rate, 74.3% [95% CI, 62.8–83.8], P < 0.0001). In the efficacy set (n = 83), ORR was 83.1% (95% CI, 73.3–90.5) with CR rate of 72.3% (95% CI, 61.4–81.6). Responses were durable: median DOR, 15.7 mo; median PFS, 15.3 mo (Table). As most pts were enrolled during the COVID-19 pandemic and 6 pts in ongoing CR died due to COVID-19, DOR, PFS, and OS were also analyzed censoring for COVID-19 deaths. In the safety set (n = 88), 86% of pts had gr ≥3 TEAE, primarily cytopenias (Table). Four gr 5 TEAEs occurred (3 related to liso-cel and/or LDC). Rate of any-grade cytokine release syndrome (CRS) was 61% (gr 3–4, 1%; no gr 5) and neurological events (NE) was 31% (gr 3–4, 9%; no gr 5). Rate of gr ≥3 infections was 15%, and prolonged cytopenia was 40%. Cellular kinetics and B-cell aplasia will be presented. Conclusions: Liso-cel demonstrated high ORR and CR rate that were durable and was well tolerated with low rates of gr ≥3 CRS, NE, and infections, thus representing a potential new treatment option for pts with high-risk, aggressive R/R MCL. The research was funded by: This study was funded by Juno Therapeutics, a Bristol-Myers Squibb Company. All authors contributed to and approved the abstract; writing and editorial assistance were provided by Allison Green, PhD, CMPP, of The Lockwood Group (Stamford, CT, USA), funded by Bristol Myers Squibb. Keyword: Cellular therapies Conflicts of interests pertinent to the abstract M. Wang Consultant or advisory role: AbbVie, Acerta Pharma, ADC Therapeutics America, Amphista Therapeutics Limited, AstraZeneca, Be Biopharma, BeiGene, BioInvent, Deciphera, DTRM Biopharma (Cayman) Limited, Genentech, InnoCare, Janssen, Kite Pharma, Leukemia & Lymphoma Society, Lilly, Merck, Miltenyi Biomedicine, Milken Institute, Oncternal, Parexel, Pepromene Bio, Pharmacyclics, VelosBio Honoraria: AbbVie, Acerta Pharma, AstraZeneca, Bantam Pharmaceutical, BeiGene, BioInvent, Bristol Myers Squibb, CAHON, Dava Oncology, Eastern Virginia Medical School, Genmab, i3Health, IDEOlogy Health, Janssen, Kite Pharma, Leukemia & Lymphoma Society, Medscape, Meeting Minds Experts, MD Education , MJH Life Sciences, Merck, Moffit Cancer Center, Nurix, Oncology Specialty Group, OncLive, Pharmacyclics, Physicians Education Resources (PER), Practice Point Communications (PPC), Scripps, Studio ER Congressi, WebMD Other remuneration: Grants or contracts from any entity: Acerta Pharma, AstraZeneca, BeiGene, BioInvent, Celgene, Genmab, Genentech, Innocare, Janssen, Juno Therapeutics, Kite Pharma, Lilly, Loxo Oncology, Molecular Templates, Oncternal, Pharmacyclics, VelosBio, Vincerx; Leadership or fiduciary role in other board, society, committee or advocacy group, paid or unpaid: Committee Member for The Leukemia & Lymphoma Society (LLS) T. Siddiqi Consultant or advisory role: Astra Zeneca, BMS, Celgene, Kite pharma, Beigene, Abbvie Honoraria: Astra Zeneca, BMS, Beigene Research funding: Astra Zeneca, BMS, Celgene, Oncternal, Ascentage pharma, Kite pharma, TG therapeutics, Pharmacyclics, Juno therapeutics L. I. Gordon Consultant or advisory role: Astra Zeneca, Karyopharm, Janssen, Epizyme, Kite-Gilead Other remuneration: Patent on gold nanoparticles for cancer; Janssen DSMB; Co-founder, Zylem Thereutics, Inc. M. Kamdar Consultant or advisory role: Astra Zeneca, Adaptive Biotechnologies, Abbvie, BeiGene, ADC Therapeutics, Syncopation Life Sciences, Bristol-Myers Squibb/Celgene, Genetech/Roche, Seattle Genetics Research funding: Novartis M. Lunning Consultant or advisory role: AbbVie, Acrotech, ADC Therapeutics, Astra Zeneca, Astellas, BMS, Caribou, CRISPR, Daiichi Sankyo, EUSA, Fate Therapeutics, Genentech, GenMab, InstilBio, Ipsen, Janssen, Kite, Loxo, Miltenyi, Morphosys, Novartis, Nurix, Pharmacyclics, Regeneron, Sanofi, SeaGen, Takeda, TG Therapeutics Research funding: BMS, Curis A. V. Hirayama Honoraria: Bristol Myers Squibb Research funding: Juno Therapeutics, a BMS company, Nektar Therapeutics, J. S. Abramson Consultant or advisory role Celgene, Novartis, Abbvie, Kite, Genetech, EMD Serono, MorphoSys, Alimera Sciences, Karyopharm Therapeutics, Bristol Myers Squibb, C4 Therpeutics, Beigene, AstraZeneca, Incyte, Bluebird Bio, Kymera, Epizyme, Genmab, Mustang Bio, Ono Pharmaceutical, Century Therapeutics, Lilly, Caribou Biosciences, Janssen, Takeda Honoraria: Regeneron, AstraZeneca, Janssen, Bristol Myers Squibb/Celgene Research funding: Seattle Genetics, AI Therapeutics, Bristol Myers Squibb/Celgene J. Arnason Consultant or advisory role Regeneron Honoraria: BMS N. Ghosh Consultant or advisory role Seagen, TG Therapeutics, AstraZeneca, Phamacyclics, Janssen, Bristol Myers Squibb, Gilead Sciences, Beigene, Incyte, Karyopharm, Roche/Genentech, Novartis, Loxo Oncology, Genmab, Adaptive Biotech, ADC Therapeutics, Syncopation Honoraria: AstraZeneca, Bristol Myers Squibb, Phamacyclics, Janssen, Epizyme Research funding: TG Therapeutics, Genentech/Roche, Bristol Myers Squibb, Gilead, Morphosys, AbbVie. A. Mehta Consultant or advisory role Gilead, Astra Zeneca, Pharmacyclics, Seattle Genetics, Incyte, Morphosys/Incyte, TG Therapeutics, Kyowa Kirin, Bei Gen, Roche-Genentech, BMS Research funding: Incyte, Takeda, Forty Seven Inc./Gilead, Juno pharmaceuticals/BMS, Celgene/BMS, Innate pharmaceuticals, Seattle Genetics, TG Therapeutics, Affimed, Merck, Kite/Gilead, Roche-Genentech, ADC, therapeutics C. Andreadis Consultant or advisory role BMS, Novartis, Kite/Gilead Other remuneration: Grants or contracts from any entity: Novartis, BMS, Genetech, Genmab, Merck A. Kostic Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb C. Dehner Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb R. Espinola Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb L. Peng Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb K. Ogasawara Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb A. Chattin Employment or leadership position: Bristol Myers Squibb Stock ownership: Bristol Myers Squibb M. L. Palomba Consultant or advisory role Novartis, Cellectar, Synthekine, Kite, Seres, Magenta, WindMIL, Rheos, Nektar, Notch, Priothera, Ceramedix, Lygenesis, Pluto Stock ownership: Seres, Notch Research funding: Seres Other remuneration: Royalties or licenses: Juno, Seres; Patents planned, issued or pending: Juno, Seres