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3490 Updated Follow-up of a Phase 1 Trial of Bispecific CART19/20 Cells for Relapsed or Refractory Non-Hodgkin Lymphoma

Program: Oral and Poster Abstracts
Session: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: Poster II
Hematology Disease Topics & Pathways:
adult, Biological therapies, Research, clinical trials, non-Hodgkin lymphoma, Lymphomas, Translational Research, Chimeric Antigen Receptor (CAR)-T Cell Therapies, B Cell lymphoma, Clinical Research, Diseases, aggressive lymphoma, Therapies, Lymphoid Malignancies, Study Population, Human
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Benjamin R Puliafito, MD1, Christopher M Walthers, PhD2*, Brenda Ji2*, Sanaz N Ghafouri, MD2*, Jacob Naparstek2*, Jacqueline Trent2*, Jia Ming Chen, PhD3*, Mobina Roshandell3*, Caitlin Harris2*, Mobina Khericha, PhD2*, Melanie Ayala Ceja2*, Christy Sidhu2*, Thomas Schweppe2*, Beata Berent-Maoz, PhD2*, Stanley B Gosliner2*, Amr Almaktari2*, Karla Nawaly2*, Martin S Allen-Auerbach, MD2*, Jonathan Said, MD4, Monica Mead, MD2, Sven de Vos, MD, PhD5*, Patricia A. Young, MD5, Caspian H. Oliai, MD6, Gary J. Schiller, MD7, John Timmerman, MD2, Antoni Ribas, MD, PhD8*, Yvonne Y Chen, PhD2* and Sarah M. Larson, MD2

1University of California, Los Angeles, Santa Monica, CA
2University of California, Los Angeles, Los Angeles, CA
3Parker Institute for Cancer Immunotherapy Center at UCLA, Los Angeles, CA
4Department of Pathology & Laboratory Medicine, University of California, Los Angeles, Los Angeles, CA
5Department of Medicine/Division of Hematology and Oncology, UCLA Medical Center, Los Angeles, CA
6Jonsson Comprehensive Cancer Center, University of California Los Angeles, Los Angeles, CA
7Division of Hematology and Oncology, University of California, Los Angeles, Los Angeles, CA
8University of California Los Angeles, Los Angeles, CA

CART19/20 was developed by engineering autologous naïve/memory T (TN/MEM) cells with a bispecific anti-CD19/CD20 chimeric antigen receptor (CAR) with the goal of mitigating antigen escape and lack of CAR T-cell persistence. We report an update of an ongoing first-in-human phase 1 clinical trial of CART19/20 for patients with relapsed/refractory non-Hodgkin lymphoma (R/R NHL) (NCT04007029).

Eligible patients were ≥18 years old with R/R diffuse large B-cell lymphoma (DLBCL) or primary mediastinal B-cell lymphoma (PMBCL) after ≥2 prior lines of therapy, or with mantle-cell lymphoma (MCL), follicular lymphoma (FL), or CLL/SLL after ≥3 prior lines of therapy. Autologous leukocytes were obtained by leukapheresis and sorted for CD14­–/CD25–/CD62L+ TN/MEM cells, followed by lentiviral transduction of the bispecific CD19/CD20 CAR. Lymphodepletion chemotherapy with fludarabine 30 mg/m2/day and cyclophosphamide 500 mg/m2/day was administered on Days −5 to −3 prior to CAR T-cell infusion. The primary endpoint was assessment of safety. Secondary endpoints were overall response rate (ORR), progression free survival (PFS), overall survival (OS), and CART19/20 transgene persistence.

As of data cutoff on July 21, 2023, 11 patients had received CART19/20 cells (6 DLBCL, including 4 transformed FL; 3 primary FL; 1 PMBCL; 1 MCL). Patients were treated at two dose levels, either 50 x 106 ± 30% CAR+ cells (8 patients) or 200 x 106 ± 30% CAR+ cells (3 patients). The median age was 58 (range: 34 to 70). Patients had received a median of 3 prior lines of therapy (range: 2 – 4). None of the treated patients had received prior CAR-T cell therapy; one patient had received a prior CD19-directed therapy. All patients had stage IV disease and 9 of 11 patients received bridging therapy. The engineered CART19/20 cells were enriched with central-memory T cells (TCM: CD45RA–/CD45RO+/CD62L+) which composed a median of 30.8% (range: 5.3 – 80.1%) of the CAR+ T-cells in the infused products.

There were no occurrences of CRS grade ≥ 2 or neurotoxicity of any grade. Six patients had grade 1 cytokine release syndrome (CRS) with a median onset of 8 days from infusion (range: 5 – 11 days). One patient met criteria for dose-limiting toxicity with persistent thrombocytopenia after Day+120. Ten of the 11 patients achieved an objective response (91% ORR), with 8 patients (73%) achieving complete response (CR). One patient with FL, who progressed 18 months after receiving CART19/20, received a second infusion of CART19/20 cells and achieved a second CR for 14.9 months. With a median follow-up of 32.3 months (range: 5.1 – 44.0 months), the median PFS (95% CI 2.6 months – not estimable) and median OS (95% CI 5.7 months – not estimable) have not been reached.

Overall, CART19/20 demonstrated a favorable safety profile with no severe CRS or neurotoxicity of any grade. Moreover, CART19/20 showed robust activity in patients with R/R NHL with durable responses seen. By utilizing a bispecific CAR and enriching for TN/MEM cells, this phase 1 trial of CART19/20 demonstrates the possibility of improving outcomes through targeting common mechanisms of CAR-T cell resistance.

Disclosures: Walthers: Orca Bio: Current Employment, Current holder of stock options in a privately-held company. Ji: CART19/20 patent: Patents & Royalties: CART19/20 patent; ImmPACT Bio: Ended employment in the past 24 months. Roshandell: Fate Therapeutics: Current Employment, Current equity holder in publicly-traded company. Schweppe: Link Immunotherapeutics: Current Employment. Berent-Maoz: Kite Pharma: Current Employment. de Vos: BeiGene: Consultancy. Oliai: Seagen: Research Funding; Arog: Research Funding; Jazz Pharmaceuticals: Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Orca Bio: Research Funding. Schiller: Stemline Therapeutics: Speakers Bureau; Geron: Research Funding; REGiMMUNE: Research Funding; Samus Therapeutics: Research Funding; Takeda: Research Funding; Mateon Therapeutics: Research Funding; Sangamo Bioscience: Research Funding; Deciphera: Research Funding; FORMA Therapeutics: Research Funding; Astellas Pharma: Consultancy, Research Funding, Speakers Bureau; Sanofi: Research Funding, Speakers Bureau; Sellas Life Sciences: Research Funding; Kite: Research Funding, Speakers Bureau; Delta-Fly Pharma: Research Funding; Daiichi Sankyo: Research Funding; AbbVie: Consultancy, Research Funding, Speakers Bureau; Precog: Research Funding; Jazz Pharmaceuticals: Consultancy, Research Funding, Speakers Bureau; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Incyte: Consultancy, Research Funding, Speakers Bureau; Stemline Therapeutics: Research Funding; Trovagene: Research Funding; Bristol Myers Squibb: Current equity holder in publicly-traded company, Research Funding, Speakers Bureau; Amgen: Current equity holder in publicly-traded company, Research Funding; Tolero Pharmaceuticals: Research Funding; Pfizer: Research Funding; Onconova Therapeutics: Research Funding; Actinium Pharmaceuticals: Research Funding; Karyopharm Therapeutics: Research Funding, Speakers Bureau; Genentech/Roche: Research Funding; Gamida Cell: Research Funding; Fujifilm: Research Funding; Constellation Pharmaceuticals: Research Funding; Celator: Research Funding; Arog: Research Funding; Actuate Therapeutics: Research Funding; Agios: Consultancy; Ono Pharmaceutical: Consultancy; Johnson & Johnson: Current equity holder in publicly-traded company; Agios: Research Funding; ElevateBio: Research Funding; Ono Pharmaceutical: Research Funding; AVM Biotechnology: Research Funding; Syros Pharmaceuticals: Research Funding; Kronos Bio: Research Funding. Timmerman: Merck & Co., Inc.: Research Funding; BMS: Other: Travel/Accommodations/Expenses, Research Funding; Oncovalent Therapeutics: Consultancy; DAVA Oncology: Consultancy; Kite/Gilead: Consultancy, Honoraria, Research Funding. Ribas: Cstone: Consultancy, Honoraria; Merck: Consultancy, Honoraria; Vedanta: Consultancy, Honoraria; Advaxis: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Appia Bio: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Apricity: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Arcus: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Compugen: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; CytomX: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Highlight: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; ImaginAb: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; ImmPACT: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; ImmuneSensor: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Inspirna: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Isoplexis: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Kite-Gilead: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Lutris: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; MapKure: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Merus: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; PACT: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Pluto: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; RAPT: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Synthekine: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Tango: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Agilent: Research Funding; Bristol-Myers Squibb: Research Funding; Arsenal Bio: Patents & Royalties. Chen: Novartis: Consultancy; Waypoint Bio: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Sonoma Biotherapeutics: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Prime Medicine: Current equity holder in publicly-traded company, Membership on an entity's Board of Directors or advisory committees; Pluto Immunotherapeutics: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Notch Therapeutics: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; Catamaran Bio: Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; ImmPACT Bio: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees; CART19/20 Patent: Patents & Royalties. Larson: TORL Biotherapeutics: Current equity holder in private company; Bristol Myers Squibb: Research Funding; Bioline: Research Funding; 1200 Pharma: Current equity holder in private company; Pfizer: Research Funding; ImmPACT Bio: Research Funding; Novartis: Research Funding; Janssen: Research Funding; AbbVie: Research Funding; Allogene: Research Funding; Ionis: Research Funding.

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