1483 Activity of IDP-023 allogeneic g-NK cells without antibody targeting in first-in-human phase 1/2 study in patients with advanced multiple myeloma or non-hodgkin lymphoma
Year: 2024
Type: conference-abstract
Abstract: Background Patients with relapsed or refractory (RR) multiple myeloma (MM) or Non-Hodgkin’s lymphoma (NHL) have poor outcomes, with overall survival generally less than 12 months after best available therapies. More effective and tolerable treatments are needed. IDP-023 is an allogeneic natural killer cell product. By natural epigenetic reprogramming, g-NK cells are FceR1g-negative and exhibit much higher antibody-dependent cytotoxicity (ADCC) following engagement of CD16 than conventional NK cells (cNK). In addition, g-NK cells are negative for the inhibitory checkpoint NKG2A and express high levels of the activating receptor NKG2C, making them uniquely suited to kill HLA-E-expressing target cells. Pre-clinical activity: Robust activity of g-NKs in combination with daratumumab has been demonstrated against MM cell lines, patient-derived primary tumor cells, and in an orthotopic xenograft myeloma model (MM.1S). IDP-023 efficacy was significantly better than expanded cNK cells1 or competitive NK cell products generated from cord blood or iPSC tested in the same model. Methods This is an open label, Phase 1/2, first-in-human, multiple ascending dose escalation, and dose-expansion study of IDP-023 administered as monotherapy +/- interleukin-2 (IL-2), and in combination with daratumumab or rituximab. (NCT06119685). Objectives: The goal of the cohorts without antibody, was to define safety and tolerability. Eligibility: Adults with RR MM who have failed ≥ 3 prior lines of therapy or with RR NHL who have failed ≥ 2 lines of systemic chemotherapy. Treatments: The cohorts described here received a matrix of two regimens (every week x3, or every other day x3) with or without IL-2. Patients received lymphodepleting chemotherapy (LD) followed by subcutaneous IL-2 and intravenous IDP0-023. Results As of 9/12/24, 9 patients were treated with IDP-023 without antibody. Eight patients received multiple doses of cells at the lowest dose and 6 also received IL-2. No DLTs were noted. Patients experienced cytopenias consistent with the LD. Two patients experienced serious AEs (febrile neutropenia) that were deemed unrelated to IDP-023. Of the patients who received IDP-023 + IL2, objective antitumor activity was seen in 4 of 5 MM patients who were heavily pretreated (3–7 prior lines of therapy, including 1 patient with prior CAR-T) and one patient with NHL who received prior CAR-T. Conclusions IDP-023 was well tolerated in both every week x3 and every other day x3 regimens. Encouraging initial activity was observed with IDP-023 + IL-2 in advanced MM and NHL, even in the absence of combination with ADCC mediating monoclonal antibodies. Acknowledgements We would like to thank the patients and their families for contributing in this study. Trial Registration NCT06119685. Reference Austin B Bigley, Shanae Spade, Nadia H Agha, Sujit Biswas, Suni Tang, Muhammad H Malik, Lu Dai, Shalaleh Masoumi, Bonell Patiño-Escobar, Martina Hale, Guy DiPierro, Ronald Martell, Byron Hann, Nina Shah, Arun P Wiita, Xinli Liu. FcεRIγ-negative NK cells persist in vivo and enhance efficacy of therapeutic monoclonal antibodies in multiple myeloma. Blood Adv 2021;15:3021–3031. Ethics Approval Participants have given informed consent before taking part in the study. The study has obtained ethics approval at all active sites and the specific IRB information is below: Site No. | Site Name | IRB Name | IRB Registration No. | IRB Approval Date | 1104 | MDACC | MDACC | IRB00000121 | 7/14/23 1393 | NEXT Virginia | Salus IRB | IRB00006833 | 9/19/23 1409 | Providence Cancer Institute | Advarra | IRB00000971 | 2/14/24 1410 | M Health Fairview - University of Minnesota Masonic Cancer| University of Minnesota| IRB00010642 | 10/4/23 | Center | 1074 | Weill Medical College of Cornell University | Advarra | IRB00000971 | 11/9/23 1425 | SCRI Oncology Partners | Castle IRB | IRB00012054 | 7/24/24 1428 | Valkyrie Clinical Trials | Advarra | IRB00000971 | 7/24/24
Authors: Krina Patel, Mitul Gandhi, Neil Sankar, Austin B Bigley, Matthew R Collinson-Pautz, Shanae Spade, Jenna Recker, Chris Gracia, Guy Dipierro, Stefanie J Mandl-Cashman, Mark Frohlich, Amiee Merino
Language: English
Subfield: Immunology
Field: Immunology and Microbiology
Domain: Life Sciences
Open Access status: gold
OpenAlex ID: W4404067302