- |||||||||| MODULE 5: Chimeric Antigen Receptor (CAR) T-Cell Therapy and Other Novel Strategies for CLL (Manchester Grand Hyatt San Diego, Seaport Ballroom EFGH; In-Person; Virtual) - Oct 5, 2024 - Abstract #ASH2024ASH_79;
Trial completion date: Jun 2027 --> May 2028 This program is supported by educational grants from AstraZeneca Pharmaceuticals LP, BeiGene Ltd and Eli Lilly.Biological rationale for the investigation of CD19- directed CAR T-cell therapy for CLL Published efficacy and safety findings with lisocabtagene maraleucel (liso-cel) for R/R CLL from the Phase I/II TRANSCEND CLL 004 trial FDA approval of liso-cel for CLL previously treated with a BTK inhibitor and a Bcl-2 inhibitor; current clinical role and optimal patient selection Early findings with other CAR T-cell-based approaches (eg, liso-cel in combination with ibrutinib, brexucabtagene autoleucel, rapcabtagene autoleucel) for heavily pretreated CLL Antitumor activity observed with bispecific antibody therapy (eg, epcoritamab, NVG-111, LAVA-051) for CLL, including in patients with Richter's transformation Other promising agents and strategies under investigation for CLL
- |||||||||| rapcabtagene autoleucel (YTB323) / Novartis
PRELIMINARY RESULTS OF AN OPEN-LABEL, MULTICENTRE, PHASE 1/2 STUDY TO ASSESS SAFETY, EFFICACY AND CELLULAR KINETICS OF YTB323 (RAPCABTAGENE AUTOLEUCEL), A RAPIDLY MANUFACTURED CAR T-CELL THERAPY TARGETING CD19 ON B CELLS, FOR SEVERE REFRACTORY SYSTEMIC LUPUS ERYTHEMATOSUS (Poster Tour 3) - Mar 29, 2024 - Abstract #EULAR2024EULAR_691; P1/2 This program is supported by educational grants from AstraZeneca Pharmaceuticals LP, BeiGene Ltd and Eli Lilly.Biological rationale for the investigation of CD19- directed CAR T-cell therapy for CLL Published efficacy and safety findings with lisocabtagene maraleucel (liso-cel) for R/R CLL from the Phase I/II TRANSCEND CLL 004 trial FDA approval of liso-cel for CLL previously treated with a BTK inhibitor and a Bcl-2 inhibitor; current clinical role and optimal patient selection Early findings with other CAR T-cell-based approaches (eg, liso-cel in combination with ibrutinib, brexucabtagene autoleucel, rapcabtagene autoleucel) for heavily pretreated CLL Antitumor activity observed with bispecific antibody therapy (eg, epcoritamab, NVG-111, LAVA-051) for CLL, including in patients with Richter's transformation Other promising agents and strategies under investigation for CLL YTB323 treatment is a single administered dose of 12.5
- |||||||||| MODULE 4: Incorporation of Chimeric Antigen Receptor (CAR) T-Cell Therapy into the Management of DLBCL (Omni San Diego, Grand Ballroom (Level 2), 4; Virtual) - Sep 23, 2023 - Abstract #ASH2023ASH_258;
Supported by educational grants from ADC Therapeutics, Genentech, a member of the Roche Group, Incyte Corporation, Kite, A Gilead Company, and Regeneron Pharmaceuticals Inc. Optimal timing for referral of patients with DLBCL for CAR T-cell therapy Major findings from Phase III studies with CAR T-cell therapy as second-line treatment for DLBCL FDA approvals of axi-cel and lisocabtagene maraleucel (liso-cel) as second-line therapy and identification of candidates for this strategy Long-term efficacy and safety data with axi-cel, tisagenlecleucel and liso-cel in multiregimen-relapsed DLBCL Spectrum, frequency and severity of adverse events (AEs) associated with CAR T-cell therapy for DLBCL, including cytokine release syndrome (CRS) and neurotoxicity Early results with other CAR T-cell platforms for DLBCL, such as rapcabtagene autoleucel
- |||||||||| rapcabtagene autoleucel (YTB323) / Novartis
Preclinical, Journal, CAR T-Cell Therapy: A Novel Autologous CAR-T Therapy, YTB323, with Preserved T-Cell Stemness Shows Enhanced CAR T-Cell Efficacy in Preclinical and Early Clinical Development. (Pubmed Central) - May 30, 2023 P1/2 Clinically, at doses 25-fold lower than tisagenlecleucel, YTB323 showed 1) promising overall safety (CRS [any-grade, 35%; grade ?3, 6%], neurotoxicity [any-grade, 25%; grade ?3, 6%]); 2) ORR of 75% and 80% for DL1 and DL2, respectively; 3) comparable CAR T-cell expansion; and 4) preservation of T-cell phenotype. Current data support continued development of YTB323 for r/r DLBCL.
- |||||||||| YTB323 / Novartis, PHE885 / Novartis, Kymriah (tisagenlecleucel-T) / Novartis
Novel Benchmark Scaling Method for First-in-Human Dose of CAR-T Therapies (Poster Board Number: W-250; Hall D) - Apr 20, 2022 - Abstract #ASGCT2022ASGCT_748; P1 Result The development of a CD19-targeted CAR-T (YTB323) and a BCMA-targeted CAR-T (PHE885) with a new optimized manufacturing method (T-ChargeTM) are used as examples...Assuming a comparable safety profile based on the same mechanism of action as CTL019, an YTB323 dose up to 2.8×107 cells (highest CTL019 dose with manageable AEs from another study UPCC03712 of 1.1×109 cells divided by 40) should be tolerable...In a second example, the target starting dose for PHE885 was derived based on preclinical comparison and clinical data generated with MCM998, another BCMA-targeted CAR-T previously tested in r/r multiple myeloma patients (NCT02546167)...Conclusion The proposed method to calculate FIH starting dose mitigates the current limitation in preclinical-to-clinical translation in CAR-T therapy. Examples of two CAR-Ts with different targets and indications demonstrated the general utility of the approach.
- |||||||||| rapcabtagene autoleucel (YTB323) / Novartis
Enrollment change, Trial completion date, Trial primary completion date, CAR T-Cell Therapy: CYTB323A12101: Phase I/II Study of Rapcabtagene Autoleucel in CLL, 3L+ DLBCL, r/r ALL and 1L HR LBCL (clinicaltrials.gov) - Aug 7, 2020 P1, N=110, Recruiting, Trial completion date: Mar 2024 --> Oct 2025 | Trial primary completion date: Mar 2024 --> Oct 2025 N=50 --> 110 | Trial completion date: Jan 2023 --> Mar 2024 | Trial primary completion date: Jan 2023 --> Mar 2024
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