Indapta's Allogeneic NK Cell Therapy Shows Promising Activity in Heavily Pretreated Multiple Myeloma Patients
核心洞察
Indapta Therapeutics (搜索) reported clinical activity of IDP-023, an allogeneic g-NK cell therapy, in patients with relapsed/refractory multiple myeloma (搜索) at the SITC Annual Meeting.
In combination with isatuximab at 10 billion cells/dose, confirmed responses were observed in 4 of 5 evaluable patients with high-risk cytogenetics and extensive prior treatments.
Notable responses included a stringent complete response in a patient with extramedullary disease who had previously progressed on both CAR-T and T-cell engager therapies.
Indapta Therapeutics (搜索) presented encouraging clinical data for IDP-023, its allogeneic gamma-minus natural killer (g-NK) cell therapy, in patients with relapsed/refractory multiple myeloma (搜索) at the Society for Immunotherapy of Cancer (SITC) Annual Meeting in Washington, DC. The data demonstrated marked clinical activity both as monotherapy and in combination with isatuximab, an anti-CD38 (搜索) monoclonal antibody.
Clinical Efficacy Results
The Phase 1/2 trial data showed particularly promising results in heavily pretreated patients with adverse prognostic features. At the second dose level of 10 billion cells per dose, IDP-023 combined with isatuximab achieved confirmed responses in 4 of 5 response evaluable patients. These patients had high-risk and ultra high-risk cytogenetics and had received extensive prior therapies.
Among the notable responses was a stringent complete response in a patient with extramedullary disease who had experienced prior progression following treatment with both CAR-T and T-cell engager therapy. This represents a significant clinical achievement given the challenging patient population and prior treatment failures.
"We are encouraged to observe this degree of clinical activity of IDP-023 alone and in combination with isatuximab," said Dr. Mark Frohlich, CEO of Indapta. "This is particularly noteworthy given the extent of prior therapies and adverse prognostic features of the patients treated."
Treatment Protocol and Safety Profile
Patients in the trial received one to three doses of IDP-023, administered with or without interleukin-2 (IL-2). The treatment demonstrated a favorable safety profile with no dose limiting toxicities observed. The most common adverse events were cytopenias, which were attributed to the conditioning chemotherapy rather than the cell therapy itself.
The data also suggested that a second cycle of IDP-023 in combination with isatuximab in select patients appeared to improve both the depth and duration of response, indicating potential for enhanced efficacy with repeated dosing.
g-NK Cell Technology Platform
IDP-023 is derived from Indapta's proprietary platform of naturally occurring g-NK cells, which are "g minus" NK cells that arise from epigenetic changes resulting from exposure to cytomegalovirus (CMV). The company preferentially expands these cells from healthy donors with low donor-to-donor variability.
The g-NK cells possess several differentiated mechanisms for killing target cells without requiring genetic engineering. These include highly robust antibody-dependent cell mediated cytotoxicity (ADCC), targeting of HLA-E (搜索) expressing cells via the NKG2C (搜索) receptor, and inherent anti-viral activity.
According to the company, g-NK cells can release dramatically more immune activating cytokines and cell-killing compounds than conventional NK cells. Preclinical studies have demonstrated that IDP-023 shows more potent and durable antitumor activity when combined with cancer targeting monoclonal antibodies compared to conventional NK cells.
Clinical Development Strategy
The presentation at SITC summarized data from both the safety run-in portion of the Phase 1 trial and the initial cohort of patients treated with the combination therapy. Indapta plans to continue enrolling patients to better characterize the response proportion and durability of treatment effect as the trial progresses toward determining the recommended Phase 2 dose.