Simcha Therapeutics has announced the commencement of two clinical trials to investigate ST-067, a decoy-resistant IL-18 cytokine, in patients with hematological malignancies. The trials will focus on acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS), and multiple myeloma, respectively, with the aim of addressing unmet needs in these challenging-to-treat cancers.
ST-067 in AML and MDS
The first study (NCT06492707), led by Dr. Elizabeth Krakow at Fred Hutch Cancer Center, will evaluate ST-067 in patients aged 18 and older who have relapsed or have persistent AML or MDS following hematopoietic cell transplantation (HCT). While HCT remains the only curative option for many AML and MDS patients, relapse occurs in approximately one-third of cases, representing a significant cause of mortality post-transplant.
This Phase 1, open-label, dose-escalation study will primarily assess dose-limiting toxicities and the proportion of patients completing four weeks of ST-067 treatment. Secondary endpoints include response rates, overall survival, and the potential for eliciting graft-versus-leukemia effects without triggering graft-versus-host disease.
ST-067 in Multiple Myeloma
The second study (NCT06588660), under the direction of Dr. Rahul Banerjee at the University of Washington and Fred Hutch Cancer Center, will explore ST-067 in combination with teclistamab (TECVAYLI®), a bispecific antibody targeting T cells, in patients with relapsed or refractory multiple myeloma. This Phase 1b, open-label study will primarily evaluate dose-limiting toxicities of ST-067 alone and in combination with teclistamab, determine optimal dosing, and assess the incidence of adverse events. Secondary endpoints will include overall response rate, duration of response, progression-free survival, overall survival, and measurable residual disease negativity.
T-cell directed therapies, including teclistamab, have become standard treatments for relapsed/refractory multiple myeloma. However, these therapies are not curative, and not all patients respond, with relapses occurring in some responders. The rationale behind this study is that ST-067, in combination with teclistamab, may enhance T-cell fitness and persistence, potentially increasing the number of patients who respond to teclistamab and prolonging the duration of response.
Preclinical Support
Preclinical data, to be presented at the 2024 American Society of Hematology (ASH) Annual Meeting & Exposition, supports the therapeutic potential of decoy-resistant IL-18 in hematological malignancies. The data demonstrate the activity of ST-067 in multiple mouse models of hematological tumors, including B-cell lymphoma, acute myeloid leukemia, and plasma cell myeloma. These findings provide a strong rationale for the ongoing clinical development of ST-067.
Simcha Therapeutics is also presenting a trials in progress poster at ASH describing the AML/MDS study, further highlighting the company's commitment to advancing novel immunotherapies for hematologic cancers.
