Background: Obe-cel is an autologous chimeric antigen receptor (CAR) T cell product with a novel CD19 binding domain CAT conferring a fast antigen off-rate designed to mitigate safety concerns and improve persistence over approved CD19 CAR T therapies. Early results from the pivotal FELIX study Phase IIA cohort (N=94) were recently presented (Roddie C et al. J Clin Oncol 2023;41[16 Suppl]:7000). We report findings from a pooled analysis of all patients (pts) treated to date with obe-cel in the FELIX Phase Ib/II study (NCT04404660), with a focus on pts with low leukemia burden prior to obe-cel infusion.
Methods: The FELIX study enrolled adults with R/R B-ALL at screening with either morphological disease ≥5% bone marrow (BM) blasts (Cohort A), or in ≥2 nd complete remission (CR)/CR with incomplete hematologic recovery (CRi) with measurable residual disease (MRD) (Cohort B), or with isolated extramedullary disease (EMD) (Cohort C). The Phase Ib part of the study enrolled Cohorts A and B; the Phase II part enrolled Cohorts A, B, and C. CAR T products were generated from leukapheresis material using an automated process. Pts received bridging therapy as needed and lymphodepletion with fludarabine (4 × 30mg/m 2) and cyclophosphamide (2 × 500mg/m 2). A target dose of 410 × 10 6 CAR T cells was infused as a split dose on Days 1 and 10 based on pre-lymphodepletion BM blast burden. The primary endpoint was overall remission rate (best response of CR/CRi by independent review). Secondary endpoints included duration of remission (DoR), MRD negative remission rate, safety, and CAR T expansion/persistence. This pooled analysis included data from pts treated with obe-cel across all cohorts in the Phase Ib/II parts of the study. Low leukemia burden was defined as morphological remission per investigator assessment (<5% BM blasts without EMD) as measured at screening or at the start of lymphodepletion.
Results: Between September 2020 and December 2022, 152 pts were enrolled and underwent leukapheresis. As of 16 March 2023, obe-cel was successfully administered to 126/152 (83%) pts (Phase Ib: Cohort A n=13, B n=3; Phase II: Cohort A n=94, B n=9, C n=7). Baseline characteristics at screening (n=126): median age 46.5 (range 20-81) yrs; Philadelphia positive B-ALL 27%; median 2 (range 1-6) prior lines of therapy; prior blinatumomab/inotuzumab 42%/32%; median BM blast burden 37% (range 0-100) including 23% pts with EMD; prior allogeneic stem cell transplant 44%. At a median follow up of 11.0 (range 0.9-30.6) months, the CR/CRi rate was 77% (95/124 response evaluable pts) with CR rate 57% (71/124). Among MRD evaluable responders, 96% achieved MRD negative status by central flow cytometry analysis. Median DoR was not reached at the current follow up. Low rates of Grade (Gr) ≥3 cytokine release syndrome (CRS; 2.4%) and/or Gr ≥3 immune effector cell associated neurotoxicity syndrome (ICANS; 7.1%) were observed. CAR T expansion was similar across the Phase Ib/II cohorts and CAR T persistence was ongoing in the majority of responders at the current follow up.
Preliminary data indicate favorable efficacy and safety in pts with low leukemia burden prior to obe-cel infusion. Among 12 pts with MRD at screening (Cohort B), two pts were not evaluable and 9/10 evaluable pts achieved CR/CRi, with 100% achieving MRD negative status by central flow cytometry analysis post obe-cel. Median DoR was not reached at the current follow up. In this subset, no Gr ≥3 CRS was observed; one pt had Gr ≥3 ICANS.
In a subset of 28 pts (across all cohorts) in morphological remission at the time of lymphodepletion, 24/27 (89%) response evaluable pts achieved CR/CRi and 100% of MRD evaluable responders achieved MRD negative CR/CRi by central flow cytometry analysis post obe-cel. Median DoR was not reached at the current follow up. In this subset, no pts experienced Gr ≥3 CRS/ICANS.
Conclusions:This pooled analysis of data from all pts treated to date in the FELIX study demonstrates high rates of CR/CRi after obe-cel treatment, durable responses (median DoR not reached), and a favorable safety profile. Preliminary data suggest better outcomes in pts with low leukemia burden at screening/lymphodepletion, with higher rates of deep MRD negative complete remission, median DoR not reached at the current follow up, no Gr ≥3 CRS and one Gr ≥3 ICANS. These data support further exploration of CAR T therapy earlier in the treatment algorithm for adults with ALL.
Disclosures
Roddie:Autolus Therapeutics: Research Funding; BMS, Novartis, Kite/Gilead, Autolus Therapeutics, Amgen: Honoraria. Sandhu:Autolus Therapeutics: Consultancy; City of Hope Medical Center: Current Employment. Tholouli:Vertex, Jazz, Pfizer, Kite/Gilead: Speakers Bureau; Autolus Therapeutics, Vertex, Jazz, Novartis: Honoraria. Shaughnessy:BMS, Sanofi: Speakers Bureau; Autolus Therapeutics, BMS: Honoraria. Barba:Jazz Pharmaceutical: Consultancy, Membership on an entity's Board of Directors or advisory committees; Nektar: Consultancy, Membership on an entity's Board of Directors or advisory committees; Miltenyi Biotech: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pierre-Fabre: Consultancy, Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees; Kite/Gilead: Consultancy, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees; Incyte: Consultancy, Membership on an entity's Board of Directors or advisory committees; Allogene: Consultancy, Membership on an entity's Board of Directors or advisory committees. Guerreiro:IIS La Fe: Current Employment; Novartis, Kite, BMS, MSD, Pierre Fabre: Consultancy. Bishop:Agios: Consultancy, Honoraria, Other: Travel support, Speakers Bureau; ADC Therapeutics: Speakers Bureau; Sana Biotechnology: Consultancy; Kite, a Gilead Company: Consultancy, Honoraria, Other: Travel support, Research Funding, Speakers Bureau; Tmunity: Research Funding; Servier: Speakers Bureau; Chimeric Therapeutics: Consultancy; Celgene: Honoraria; Sanofi: Honoraria, Speakers Bureau; Novartis: Consultancy, Honoraria, Other: Travel support, Research Funding; BMS: Honoraria, Other: Travel support, Speakers Bureau; Iovance: Consultancy; Bluebird Bio: Consultancy; WindMIL Therapeutics: Consultancy; Autolus: Consultancy, Research Funding; Arcellx: Consultancy, Research Funding; Triumvira: Research Funding; Immatics: Research Funding; CRISPR Therapeutics: Consultancy, Research Funding; KITE/Gilead, Novartis, CRISPR Therapeutics, Autolus Therapeutics, BMS/JUNO Therapeutics, Incyte, Sana Biotechnology, Iovance Biotherapeutics, In8bio, Chimeric Therapeutics: Consultancy, Membership on an entity's Board of Directors or advisory committees; BMS, Kite/Gilead, Servier, AstraZeneca, ADC Therapeutics, Incyte: Speakers Bureau; Incyte: Honoraria, Other: Travel support, Speakers Bureau. Yared:AAACTT (Board of Directors), NHLBI DSMB (Board member): Membership on an entity's Board of Directors or advisory committees; Institution research funding as a PI on pharma- sponsored clinical trials opened at the University of Maryland: Research Funding; Sanofi, Incyte, Kadmon, Omeros: Consultancy; University of Maryland: Current Employment. Ghobadi:Atara: Consultancy; Genentech, Inc.: Research Funding; BMS: Consultancy; CRISPR Therapeutics: Consultancy; Kite/Gilead: Consultancy, Honoraria, Research Funding; Wugen Inc: Consultancy; Amgen: Consultancy, Research Funding. Yallop:Amgen: Other: Educational support; Servier: Research Funding; King's College Hospital NHS Foundation Trust: Current Employment; Autolus Therapeutics, Kite/Gilead, Pfizer: Consultancy. Logan:AbbVie, Amgen, Actinium, BMS, Pfizer, Sanofi, Takeda: Consultancy; Amgen, Autolus Therapeutics, Kadmon, Kite, Pharmacyclics, Talaris: Research Funding. Beitinjaneh:Kite: Honoraria. Pantin:Omeros: Honoraria; Orca Bio: Research Funding; Omeros, Sanofi: Speakers Bureau. Chaganti:Janssen, Kite/Gilead: Research Funding; Takeda, Kite/Gilead, F. Hoffmann-La Roche Ltd, Atara Bio, Orion Pharma, Adicet Bio, Incyte, AbbVie, Novartis, Pierre-Fabre, Miltenyi Bio: Honoraria; Takeda, Kite/Gilead, Incyte, AbbVie, Pierre Fabre: Speakers Bureau; Takeda, Kite-Gilead, Abbvie, Pierre Fabre: Other: Meeting attendance support; Takeda, Kite/Gilead, F. Hoffmann-La Roche Ltd, Atara Bio, Orion Pharma, Adicet Bio, Incyte, AbbVie, Pierre-Fabre, Miltenyi Bio, BMS-Celgene: Consultancy. Malladi:Gilead: Honoraria, Other: travel support, Speakers Bureau; Novartis: Honoraria, Speakers Bureau. Menne:Kite/Gilead, Takeda, Janssen, F. Hoffmann-La Roche Ltd, Servier, Novartis, Celgene/BMS, Pfizer, Incyte: Speakers Bureau; Kite/Gilead, Amgen, Novartis, Pfizer, Celgene/BMS, Daiichi Sankyo, Atara, Roche, Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen, Jazz, Pfizer, Bayer, Kyowa Kirin, Celgene/BMS, Kite/Gilead, Janssen, Takeda: Other: Travel grants; Janssen, AstraZeneca, Novartis: Research Funding; Kite/Gilead, Amgen, Novartis, Pfizer, Celgene/BMS, Daiichi Sankyo, Atara, F. Hoffmann-La Roche Ltd, Janssen, BMS, CTI BioPharma, Blueprint Medicines, Sanofi-Aventis, Spark Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months, Honoraria. Hodby:Astellas: Honoraria. Gundabolu:Autolus Therapeutics: Research Funding; GERN: Current equity holder in publicly-traded company; BMS, CTI BioPharma, Blueprint Medicines, Sanofi-Aventis, Spark Therapeutics: Consultancy. Mountjoy:Colorado Blood Cancer Institute: Current Employment. Abedin:AltruBio: Research Funding; Daichii Sankyo: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Incyte: Research Funding; Actinium Pharmaceutical: Research Funding; Servier: Consultancy, Honoraria. Alkhateeb:Mayo Clinic: Current Employment. Shah:Moffitt Cancer Center: Current Employment; Takeda, AstraZeneca, Adaptive Biotechnologies, BMS/Celgene, Novartis, Pfizer, Amgen, Precision Biosciences, Kite/Gilead, Jazz Pharmaceuticals, Century Therapeutics, Deciphera, Autolus Therapeutics, Lilly, Pepromene: Consultancy; Celgene, Novartis, Pfizer, Janssen, Seattle Genetics, AstraZeneca, Stemline Therapeutics, Kite/Gilead: Other: Travel, Accommodations, Expenses; Pharmacyclics/Janssen, Spectrum/Acrotech, BeiGene, Gilead Sciences: Honoraria; Incyte, Jazz Pharmaceuticals, Kite/Gilead, SERVIER: Research Funding; DSMC, Pepromene Bio: Membership on an entity's Board of Directors or advisory committees. Lao-Sirieix:AstraZeneca, Autolus Therapeutics: Divested equity in a private or publicly-traded company in the past 24 months; Medical Research Council, Medtronic: Patents & Royalties; AstraZeneca: Ended employment in the past 24 months; Autolus Therapeutics: Current Employment. Pittari:Autolus Therapeutics: Current Employment, Current equity holder in publicly-traded company, Divested equity in a private or publicly-traded company in the past 24 months. Saxena:Autolus Therapeutics: Current Employment. Zhang:Autolus Therapeutics: Current Employment; Autolus Therapeutics, Novartis: Current equity holder in publicly-traded company. Brugger:Autolus Therapeutics: Current Employment, Current equity holder in publicly-traded company. Pule:Autolus Therapeutics: Current Employment, Current equity holder in publicly-traded company, Other: Entitled to royalty payments from related intellectual property. Park:Amgen: Consultancy; Takeda: Consultancy, Research Funding; Autolus Therapeutics: Research Funding; Intella: Consultancy; Servier: Consultancy, Research Funding; Kite: Consultancy; Minerva Bio: Consultancy; Genentech, Inc.: Research Funding; GC Cell: Membership on an entity's Board of Directors or advisory committees; Fate Therapeutics: Research Funding; Be Biopharma: Consultancy; Artiva Biotherapeutics: Consultancy, Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Affyimmune: Consultancy; BeiGene: Consultancy; Bright Pharmacetuicals: Consultancy; Curocell: Consultancy; Sobi: Consultancy, Research Funding; Allogene: Consultancy, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy; Incyte: Research Funding. DeAngelo:AbbVie, Glycomimetics, Novartis, Blueprint Pharmaceuticals: Research Funding; Amgen, Autolus Therapeutics, Agios, Blueprint, Forty-Seven, Gilead, Incyte, Jazz, Novartis, Pfizer, Servier, Takeda: Consultancy. Jabbour:Ascentage Pharma Group: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria, Research Funding; Amgen: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; Bristol-Myers Squibb: Consultancy, Honoraria, Research Funding; Abbvie: Consultancy, Honoraria, Research Funding; Adaptive Biotech: Consultancy, Honoraria, Research Funding; Pfizer: Consultancy, Honoraria, Research Funding; Hikma Pharmaceuticals: Consultancy, Honoraria, Research Funding.
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