No dose-limiting toxicities occurred in patients with relapsed/refractory multiple myeloma (MM) who were treated with agenT-797, a novel allogeneic invariant natural killer T-cell therapy, according to a presentation at the 2022 Society for Immunotherapy of Cancer Annual Meeting.
AgenT-797 is a “scalable, off-the-shelf therapy that retains potent cytotoxicity after cryopreservation,” the authors, led by Don Stevens, MD, of the Norton Cancer Institute, wrote.
The researchers analyzed data from two ongoing phase I studies of agenT-797, one of which evaluated it as a monotherapy in 12 patients with relapsed/refractory MM, while the other assessed agenT-797 alone or in combination with pembrolizumab or nivolumab in 25 patients with relapsed/refractory solid tumors.
Patients with relapsed/refractory MM received agenT-797 at dose levels of 1.4×106 cells/kg (n=3), 4.3×106 cells/kg (n=6), or 1.4×107 cells/kg (n=3) after having failed at least three prior treatments, including a proteasome inhibitor, immunomodulatory agent, and an anti-CD38 antibody. They received a single dose of agenT-797, without lymphodepletion, in two dose-escalating cohorts. These patients had a median age of 55 years and received a median of five prior lines of therapy. Of the 12 patients treated, eight were evaluable (see TABLE 1).
|TABLE 1. AgenT-797 Dose Levels and Best Overall Responses in Patients with Relapsed/Refractory Multiple Myeloma|
|Patient||AgenT-797 Dose||Prior Lines of Therapy||Prior Immunotherapies||Best Overall Response|
|1||1.4×106 cells/kg||6||Daratumumab, nivolumab||Stable disease for 10 months|
|2||1.4×106 cells/kg||6||Daratumumab, elotuzumab||Progressive disease|
|3||1.4×106 cells/kg||4||Daratumumab||Progressive disease|
|4||4.3×106 cells/kg||4||Daratumumab||Progressive disease|
|5||4.3×106 cells/kg||3||Daratumumab||Progressive disease|
|6||4.3×106 cells/kg||7||Daratumumab, elotuzumab||Stable disease for two months with response ongoing|
|7||1.4×107 cells/kg||2||Daratumumab||Progressive disease|
|8||1.4×107 cells/kg||6||Daratumumab||Progressive disease|
No dose-limiting toxicities occurred with agenT-797. The lack of dose-limiting toxicities indicates that agenT-797 has “favorable” tolerability in patients with relapsed/refractory MM, according to Dr. Stevens and colleagues.
AgenT-797 “can be administered without lymphodepletion, is tolerable in patients with [relapsed/refractory] MM after at least three prior lines of therapy and shows early signals of durable disease stabilization,” they concluded.
Stevens D, Mo C, Garmezy B, et al. Phase I studies of agenT-797, a novel allogeneic invariant natural killer T (iNKT) cell therapy, for the treatment of patients with solid tumors or multiple myeloma. Abstract #647. Presented at the 2022 Society for Immunotherapy of Cancer Annual Meeting; November 8-12, 2022, Boston, MA.