Interim results from the ELiPSE-1 study: A phase 1, multicenter, open-label study of CNTY-101 in subjects with relapsed or refractory CD19-positive B-cell malignancies

• Published in: Journal of clinical oncology Vol. 42; no. 16_suppl; p. 7023
• Main Authors: Namburi, Swathi, Latif, Tahir, Oluwole, Olalekan O., Cross, Scott J., Simmons, Gary, Iragavarapu, Chaitanya, Hu, Bei, Jih, Gloria, Bullaughey, Kevin, Das, Poulomee A, Devlin, Elizabeth, Flowers, Kevin, Fountaine, Thomas, Koumenis, Iphigenia, Ramachandran, Indu, Rothman, Sarah, Trede, Nikolaus S, Yee, Stephanie, Moyo, Tamara Kay
• Format: Journal Article
• Language: English
• Published: American Society of Clinical Oncology 01.06.2024
• DOI: 10.1200/JCO.2024.42.16_suppl.7023
• ISSN: 0732-183X

7023Background: CNTY-101 is an allogeneic, iPSC-derived anti-CD19 Chimeric Antigen Receptor NK (CAR-iNK) cell product with Allo-Evasion edits to avoid host rejection. Potential benefits of CNTY-101 include immediate availability for treatment, repeat dosing without the need for lymphodepletion, and the potential for improved safety over T-cell based therapies. The first-in-human Phase 1 clinical trial of CNTY-101, ELiPSE-1 (NCT05336409), evaluates safety, preliminary efficacy, PK, and translational biomarkers in patients with CD19-positive B-cell malignancies. Methods: Subjects with R/R aggressive and indolent B-cell NHL received lymphodepletion (LDC) followed by assignment to 100e6, 300e6 or 1e9 cells at either Day 1 (Schedule A) or Days 1, 8 and 15 (Schedule B). Eligible subjects (ie, achieved SD or better at Day 28 by PET/CT) can receive additional cycles, with or without one additional regimen of LDC. Subjects also receive daily subcutaneous injections of IL-2 for 8 days (A) or 4 days (B) following each infusion. Results: At time of abstract submission, 10 subjects have been treated (n=4 DL1A; n=3 DL2A; n=2 DL3A; n=1 DL2B). Three subjects (1 at DL1A, 2 at DL2A) received additional cycle(s) of CNTY-101. Three subjects have not yet been evaluated for full safety and efficacy within the DLT window. Seven subjects (n=5 DLBCL; n=1 FL; n=1 MZL) had data available as of the data cut (Nov 30, 2023). All had stage 4 disease, 6/7 were refractory to last line of therapy, with a median of 4 (2-5) prior lines of therapy including CAR T (3/7). No DLTs, GvHD or ICANs were observed. Two subjects had cytokine release syndrome (n=1 Gr 1, n=1 Gr 2), all responding promptly to treatment. ORR/CRR was 25%/25% for 100e6 cells (DL1A) and 67%/33% for 300e6 cells (DL2A). Dose escalation is ongoing. In subjects from all three dose levels, CNTY-101 rapidly traffics out of circulation after infusion and is observed via cell-free DNA on Day 3 and detected up to 28 days. CNTY-101 persistence was not adversely impacted when given without lymphodepletion in two subjects who received additional cycles of CNTY-101. Induction of functional humoral immunogenicity against CNTY-101 was not observed at any of the dose levels, regardless of single or multiple cycles of CNTY-101. Adaptive immune responses were observed in the tumor microenvironment on Day 8. Conclusions: CNTY-101 administered as a single dose in multiple cycles has demonstrated a manageable safety profile and preliminary evidence of efficacy. Allo-Evasion edits may allow for repeat dosing for multiple cycles without allorejection in the absence of lymphodepletion. Preliminary efficacy supports dosing at higher dose levels and with more dose-intense regimens. Updated safety, efficacy, PK, and CNTY-101's impact on tumor for DL3A and DL2B will be provided. Clinical trial information: NCT05336409.