Shattuck Labs to Present New Data on SL-172154 Clinical Trial in HR-MDS and TP53m AML at EHA 2024

Shattuck Labs, Inc., a clinical-stage biotechnology firm specializing in the development of bifunctional fusion proteins, has reported new data from its Phase 1B dose expansion clinical trial involving the drug SL-172154 combined with Azacitidine (AZA) for the treatment of untreated higher-risk myelodysplastic syndromes (HR-MDS) and TP53-mutated acute myeloid leukemia (TP53m AML). This data will be highlighted in a poster presentation at the EHA 2024 Congress, scheduled for June 13-16, 2024, both virtually and in Madrid, Spain.

According to Dr. Lini Pandite, Chief Medical Officer of Shattuck, the company completed initial patient enrollment in late 2023 and has since expanded the study cohorts for both HR-MDS and TP53m AML. By February 1, 2024, the data indicated encouraging response rates, with an increase in complete response (CR) rates and overall response rates (ORR) in HR-MDS and TP53m AML patients, respectively. The company plans to provide further updates at the EHA Annual Congress based on additional data expected in the second quarter of 2024.

Key findings from the Phase 1B trial include:

For HR-MDS, the study evaluated 23 patients, 20 of whom had TP53 mutations and 21 had complex karyotypes. Among these, seven patients had therapy-related MDS. The ORR was 65%, with nine patients achieving CR within a median time of 16 weeks. None of these patients showed disease progression by the data cutoff date. Sixteen patients were still undergoing treatment.

In the TP53m AML cohort, 14 patients were evaluable, 11 of whom had secondary AML. The ORR in this group was 36%. Two patients achieved a CR with a median time to CR of 8.7 weeks, and another patient reached CR with incomplete hematologic recovery (CRi). Two patients showed partial responses (PR). Four responders were successfully bridged to hematopoietic cell transplantation (HCT), including one patient with CR, one with CRi, and two with PR. Six patients remained in treatment, including one in CR, with no disease progression observed in responders by the cutoff date.

The median duration of response and overall survival have not yet been reached for both HR-MDS and TP53m AML patients as of the last data cutoff.

On the safety front, SL-172154 demonstrated an acceptable safety profile. The most common treatment-emergent adverse events (TEAEs) related to the drug were infusion-related reactions (IRRs), reported in 18 patients (46%), primarily at Grade 1 or 2 severity, with only two Grade 3 events. Other significant TEAEs included fatigue (observed in five patients) and hypokalemia (four patients). Cytokine release syndrome was reported in two HR-MDS patients, one case each at Grade 2 and Grade 3. Serious Grade 3/4 TEAEs were noted in 11 patients (28%), with fatigue, febrile neutropenia, and IRR being the most frequent. Discontinuation of SL-172154 occurred in two patients following severe adverse events: one with a Grade 4 myocardial infarction and another with a Grade 5 cardiac arrest, both of whom had pre-existing cardiovascular conditions and other risk factors.

SL-172154 is an investigational ARC® fusion protein designed to inhibit the CD47/SIRPα checkpoint interaction while activating the CD40 costimulatory receptor to enhance anti-tumor immune responses. It is being evaluated in various Phase 1 trials for patients with platinum-resistant ovarian cancer and those with HR-MDS and AML.

Shattuck Labs, with headquarters in both Austin, Texas, and Durham, North Carolina, is committed to advancing its biologic therapies for cancer and autoimmune diseases. The company continues to push forward with its clinical development programs, aiming to offer new therapeutic options for patients with these challenging conditions.