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754 KTE-X19, an Anti-CD19 Chimeric Antigen Receptor (CAR) T Cell Therapy, in Patients (Pts) With Relapsed/Refractory (R/R) Mantle Cell Lymphoma (MCL): Results of the Phase 2 ZUMA-2 StudyClinically Relevant Abstract

Program: Oral and Poster Abstracts
Type: Oral
Session: 623. Mantle Cell, Follicular, and Other Indolent B-Cell Lymphoma—Clinical Studies: Mantle Cell Lymphoma: Frontline and Relapsed Therapies
Hematology Disease Topics & Pathways:
Diseases, Biological, Adult, CRS, survivorship, Therapies, neurotoxicity, Adverse Events, CAR-Ts, Mantle Cell Lymphoma, Non-Hodgkin Lymphoma, Study Population, Lymphoid Malignancies, Clinically relevant
Monday, December 9, 2019: 3:30 PM
Hall D, Level 2 (Orange County Convention Center)

Michael L. Wang, MD1, Javier Munoz, MD2*, Andre Goy, MD3, Frederick L. Locke, MD4, Caron A. Jacobson, MD, MMSc5*, Brian T. Hill, MD6, John M. Timmerman, MD7, Houston Holmes, MD8*, Samantha Jaglowski, MD, MPH9, Ian W. Flinn, MD, PhD10, Peter A. McSweeney, MD11*, David B. Miklos, MD, PhD12, John M. Pagel, MD, PhD, DSc13, Marie Jose Kersten, MD, PhD14, Weimin Peng, MS15*, Lianqing Zheng, PhD15*, John M. Rossi, MS15*, Rajul K. Jain, MD15*, Arati V. Rao, MD15* and Patrick M Reagan, MD16

1The University of Texas MD Anderson Cancer Center, Houston, TX
2Banner MD Anderson Cancer Center, Gilbert, AZ
3Department of Hematology & Oncology, John Theurer Cancer Center, Hackensack University Medical Center, Hackensack, NJ
4Department of Blood and Marrow Transplant and Cellular Immunotherapy, Moffitt Cancer Center, Tampa, FL
5Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA
6Department of Hematology and Medical Oncology, Taussig Cancer Institute, Cleveland Clinic Foundation, Cleveland, OH
7UCLA David Geffen School of Medicine, Los Angeles, CA
8Texas Oncology, Dallas, TX
9The Ohio State Univ. Comprehensive Cancer Center, Columbus, OH
10Sarah Cannon Research Institute, Nashville, TN
11Colorado Blood Cancer Institute, Denver, CO
12Stanford University School of Medicine, Stanford, CA
13Center for Blood Disorders and Stem Cell Transplantation, Swedish Cancer Institute, Seattle, WA
14Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands
15Kite, a Gilead Company, Santa Monica, CA
16Wilmot Cancer Institute Division of Hematology/Oncology, University of Rochester Medical Center, Rochester, NY

Background: Outcomes with salvage regimens in pts with MCL who progress after Bruton tyrosine kinase inhibitor (BTKi) therapy are poor, with a median overall survival (OS) of 5.8 months (Martin, et al. Blood. 2016) and few pts proceeding to allogeneic stem cell transplant. ZUMA-2 is a Phase 2, registrational, multicenter, global study evaluating KTE-X19, an autologous anti-CD19 CAR T cell therapy, in pts with R/R MCL who received 1-5 prior therapies, including a BTKi. Here, we present interim efficacy and safety results from ZUMA-2.

Methods: Eligible adults (aged ≥ 18 years) with R/R MCL had an ECOG score of 0 – 1 and ≤ 5 prior therapies, including chemotherapy, an anti-CD20 antibody, and a BTKi. Pts underwent leukapheresis and conditioning chemotherapy (cyclophosphamide 300 mg/m2/d and fludarabine 30 mg/m2/d for 3 days) followed by a single infusion of KTE-X19 at a target dose of 2 × 106 CAR T cells/kg. Pts could have received bridging therapy with dexamethasone, ibrutinib, or acalabrutinib after leukapheresis and before conditioning chemotherapy at the investigator’s discretion. The primary endpoint was objective response rate (ORR [complete response (CR) + partial response]) assessed by an Independent Review Committee according to the Lugano Classification (Cheson, et al. J Clin Oncol. 2014). Interim efficacy endpoints were investigator-assessed using the revised IWG Response Criteria for Malignant Lymphoma (Cheson, et al. J Clin Oncol. 2007). Key secondary endpoints were duration of response (DOR), progression-free survival (PFS), OS, frequency of adverse events (AEs), levels of CAR T cells in blood, and levels of cytokines in serum. Efficacy and safety analyses included all pts who received KTE-X19. A total of 60 pts received KTE-X19; here, we present results in pts who had ≥ 1 year of follow-up. Updated safety and efficacy results in the full 60 pts, including pts who received revised AE management with the aim of decreasing toxicity, will be reported in the presentation.

Results: As of May 30, 2018, 28 pts received KTE-X19 with ≥ 1 year of follow-up (median 13.2 months [range, 11.5 – 18.5]). The median age was 65 years (range, 50 – 75) and 86% of pts were male. Forty-three percent of pts had ECOG score of 1, 21% had blastoid morphology, 82% had stage IV disease, 50% had intermediate/high-risk MIPI, 86% received a median of 4 (range, 1 – 5) prior therapies, and 57% were refractory to last prior therapy. In 20/28 pts with available data, the median Ki-67 index was 38% (range, 5% – 80%). Eight pts received bridging therapy; all had disease present post-bridging.

Investigator-assessed ORR was 86% (95% CI, 67% – 96%) with a CR rate of 57% (95% CI, 37% – 76%). As of May 30, 2018, 75% of responders remained in response and 64% of treated pts had ongoing responses. The 12-month estimates of DOR, PFS and OS were 83% (95% CI, 60% – 93%), 71% (95% CI, 50% – 84%), and 86% (95% CI, 66% – 94%), respectively and the medians were not reached. The most common Grade ≥ 3 AEs (≥ 20% of pts) were anemia (54%), platelet count decreased (39%), neutropenia (36%), neutrophil count decreased (32%), white blood cell count decreased (29%), encephalopathy (25%), and hypertension (21%). Grade 3/4 cytokine release syndrome (CRS) assessed by Lee et al. (Blood. 2014) was reported in 18% of pts, most commonly manifesting as hypotension (14%), hypoxia (14%), and pyrexia (11%). Grade 3/4 neurologic events (NE) were reported in 46% of pts and included encephalopathy (25%), confusional state (14%), and aphasia (11%). No Grade 5 CRS or NE occurred. All CRS events and most NE (15/17 pts) were reversible. Median time to onset and resolution of CRS was 2 days (range, 1 – 7) and 13 days (range, 4 – 60), respectively. Median time to onset of NE was 6 days (range, 1 – 15) and median time to resolution was 20 days (range, 9 – 99). There was 1 Grade 5 AE of organizing pneumonia that was considered related to conditioning chemotherapy. Median CAR T cell levels as measured by peak and area under the curve were 99 cells/µL (range, 0.4 – 2589) and 1542 cells/µL (range, 5.5 – 27239), respectively. Peak CAR T cell expansion was observed between Days 8 and 15 and declined over time.

Conclusions: ZUMA-2 is the first multicenter Phase 2 study of CAR T cell therapy in pts with R/R MCL. With ≥ 1 year of follow-up, KTE-X19 demonstrated significant and durable clinical benefit, including a majority of pts achieving CR, and a manageable safety profile in pts with R/R MCL for whom there are no curative treatment options.

Disclosures: Wang: VelosBio: Research Funding; Guidepoint Global: Consultancy; BioInvent: Consultancy, Research Funding; Kite Pharma: Consultancy, Research Funding; Acerta Pharma: Consultancy, Research Funding; MoreHealth: Consultancy, Equity Ownership; AstraZeneca: Consultancy, Honoraria, Research Funding, Speakers Bureau; Pharmacyclics: Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Loxo Oncology: Research Funding; Celgene: Honoraria, Research Funding; Juno Therapeutics: Research Funding; Aviara: Research Funding; Dava Oncology: Honoraria. Munoz: Pharmacyclics /Janssen: Consultancy, Research Funding, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Merck: Consultancy; Kyowa: Consultancy, Honoraria, Speakers Bureau; Seattle Genetics: Consultancy, Honoraria, Research Funding, Speakers Bureau; Celgene/Juno: Consultancy, Research Funding; Genentech: Consultancy, Research Funding, Speakers Bureau; Kite/Gilead: Consultancy, Research Funding, Speakers Bureau; Bristol-Myers Squibb: Consultancy; Alexion: Consultancy; Pfizer: Consultancy; Fosunkite: Speakers Bureau; AstraZeneca: Speakers Bureau; Portola: Research Funding; Incyte: Research Funding. Goy: Astrazenca: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; University of Nebraska: Research Funding; Hakensackumc: Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Hackensack University Medical Center, RCCA: Employment; COTA: Equity Ownership, Membership on an entity's Board of Directors or advisory committees, Other: leadership role for profit healthcare company; Genentech: Other: Grants outside of the submitted work, Research Funding; Pharmacyclics/Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants outside of the submitted work, Research Funding; Kite, a Gilead Company: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants outside of the submitted work; Takeda: Other: Grants outside of the submitted work; Acerta: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Grants outside of the submitted work, Research Funding. Locke: Kite: Other: Scientific Advisor; Novartis: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy. Jacobson: Humanigen: Consultancy, Other: travel support; Novartis: Consultancy, Honoraria, Other: travel support; Bayer: Consultancy, Other: travel support; Precision Biosciences: Consultancy, Other: travel support; Kite, a Gilead Company: Consultancy, Honoraria, Other: travel support; Celgene: Consultancy, Other: travel support; Pfizer: Research Funding. Hill: Amgen: Research Funding; Pharmacyclics: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Gilead: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Kite: Consultancy, Honoraria; Genentech: Consultancy, Research Funding; Abbvie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; TG therapeutics: Research Funding; Takeda: Research Funding; AstraZeneca: Consultancy, Honoraria; Seattle Genetics: Consultancy, Honoraria; Celegene: Consultancy, Honoraria, Research Funding. Timmerman: Spectrum Pharmaceuticals: Research Funding; Kite, A Gilead Company: Consultancy, Honoraria, Other: travel support, Research Funding; Merck: Research Funding; ImmunGene: Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Other: travel support, Research Funding. Holmes: ADC Therapeutics: Research Funding; Kite, A Gilead Company: Consultancy, Speakers Bureau; Genentech: Research Funding; Janssen: Consultancy; Rigel: Consultancy, Speakers Bureau; Bayer: Consultancy; Novartis: Research Funding; Unum: Research Funding; Gilead: Consultancy; Juno: Consultancy; Seattle Genetics: Research Funding, Speakers Bureau. Jaglowski: Kite: Consultancy, Other: advisory board, Research Funding; Unum Therapeutics Inc.: Research Funding; Juno: Consultancy, Other: advisory board; Novartis: Consultancy, Other: advisory board, Research Funding. Flinn: F. Hoffmann-La Roche Ltd: Research Funding; AbbVie, Seattle Genetics, TG Therapeutics, Verastem: Consultancy; TG Therapeutics, Trillum Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, UnumTherapeutics, MorphoSys, AG: Research Funding; TG Therapeutics, Trillum Therapeutics, Abbvie, ArQule, BeiGene, Curis, FORMA Therapeutics, Forty Seven, Merck, Pfizer, Takeda, Teva, Verastem, Gilead Sciences, Astra Zeneca (AZ), Juno Therapeutics, UnumTherapeutics, MorphoSys, AG: Research Funding; Acerta Pharma, Agios, Calithera Biosciences, Celgene, Constellation Pharmaceuticals, Genentech, Gilead Sciences, Incyte, Infinity Pharmaceuticals, Janssen, Karyopharm Therapeutics, Kite Pharma, Novartis, Pharmacyclics, Portola Pharmaceuticals: Research Funding. McSweeney: Fred Hutchinson Cancer Research Center: Patents & Royalties; Colorado Blood Cancer Institute Medical Group: Employment; Kite, a Gilead Company: Consultancy, Honoraria, Research Funding, Speakers Bureau. Miklos: AlloGene: Consultancy; Janssen: Consultancy; Pharmacyclics: Consultancy, Patents & Royalties, Research Funding; Kite, A Gilead Company: Consultancy, Research Funding; Celgene-Juno: Consultancy; Novartis: Consultancy; Miltenyi: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy, Research Funding; Becton Dickinson: Consultancy; Precision Bioscience: Consultancy. Pagel: Gilead Sciences: Consultancy; Pharmacyclics: Consultancy; AstraZeneca: Consultancy. Kersten: Amgen: Other: Travel grants, honorarium, or advisory boards; Roche: Other: Travel grants, honorarium, or advisory boards; Janssen/Cilag: Other: Travel grants, honorarium, or advisory boards; Roche: Consultancy, Research Funding, Travel grants, honorarium, or advisory boards; Celgene: Other: Travel grants, honorarium, or advisory boards; Celgene: Consultancy, Research Funding; Bristol Myers Squibb: Other: Travel grants, honorarium, or advisory boards; MSD: Other: Travel grants, honorarium, or advisory boards; Takeda: Consultancy, Research Funding; Gilead: Other: Travel grants, honorarium, or advisory boards; Kite: Consultancy, Other: Travel grants, honorarium, or advisory boards; Novartis: Consultancy, Other: Travel grants, honorarium, or advisory boards. Peng: Kite, A Gilead Company: Employment. Rossi: Kite, A Gilead Company: Employment. Jain: Vida Ventures: Employment; Kite, A Gilead Company: Employment, Equity Ownership, Other: Travel support; Amgen: Equity Ownership. Rao: Kite, A Gilead Company: Employment. Reagan: Kite, A Gilead Company: Consultancy; Curis: Consultancy; Seattle Genetics: Research Funding.

OffLabel Disclosure: ZUMA-2 is a clinical trial evaluating KTE-X19, an investigational CAR T cell therapy

*signifies non-member of ASH