– Positive interim data from Phase 1B clinical trial of SL-172154 in combination with pegylated liposomal doxorubicin (PLD) in platinum-resistant ovarian cancer (PROC) demonstrated an acceptable safety profile and encouraging anti-tumor activity that compares favorably to PLD as a monotherapy; expect to complete enrollment in this expansion cohort in the fourth quarter of 2023 –
– Topline data from Phase 1A/B clinical trial of SL-172154 in relapsed/refractory (R/R) acute myeloid leukemia (AML) and higher-risk myelodysplastic syndromes (HR-MDS) patients as monotherapy and in combination with Azacitidine (AZA) to be presented in a poster presentation at the American Society of Hematology (ASH) Annual Meeting; demonstrated monotherapy response and anti-leukemic activity with an acceptable safety/tolerability profile –
– Completed enrollment in frontline expansion cohort in TP53 mutant AML in the third quarter and expect to complete planned enrollment in the frontline HR-MDS cohort in the fourth quarter of 2023; interim data from both cohorts expected in the fourth quarter of 2023 –
– Conference call and webcast to be held today, November 9th at 8:00 a.m. ET –
AUSTIN, TX and DURHAM, NC, Nov. 09, 2023 (GLOBE NEWSWIRE) -- Shattuck Labs, Inc. (Shattuck) (NASDAQ: STTK), a clinical-stage biotechnology company pioneering the development of bi-functional fusion proteins as a new class of biologic medicine for the treatment of patients with cancer and autoimmune disease, today reported financial results for the quarter ended September 30, 2023, and provided recent business highlights.
“We are encouraged by the interim data for SL-172154 in combination with PLD in a group of PROC patients with advanced disease. These data are early, and require both additional patients and longer follow-up, but provide reason for optimism in this study because an overall response rate of 25-30% with SL-171514 in combination with PLD is distinct from a benchmark response rate of 4% with PLD alone,” said Taylor Schreiber, M.D., Ph.D., Chief Executive Officer of Shattuck. “We look forward to sharing data from our ongoing combination clinical trial with AZA in frontline HR-MDS and TP53 mutant AML in December.”
SL-172154 Clinical Update: Phase 1B Clinical Trial of SL-172154 in Combination with PLD in PROC
Key Takeaways: Observed three partial responses (one confirmed with 58% reduction in the sum of target lesion diameters and two unconfirmed with 100% and 31% reductions in the sum of the target lesion diameters) out of 11 evaluable patients with PROC for SL-172154 in combination with PLD. The initial data suggest SL-172154 had an acceptable safety profile in combination with PLD.
- Data overview: As of the data cut-off date of October 31, 2023, 16 adult patients with PROC have been dosed in the ongoing Phase 1B clinical study, of which 11 patients were evaluable for response. Patients had a median of 1.5 prior lines of systemic therapy, 47% had bulky disease measuring >5 cm, 56% were pre-treated with bevacizumab and 88% were resistant to frontline platinum regimen.
- Preliminary anti-tumor activity: As of the data cut-off date of October 31, 2023, three partial responses (one confirmed, two unconfirmed) had been observed for SL-172154 in combination with PLD. As of November 9, 2023, both patients with unconfirmed partial responses remain on study and have not reached the date of confirmatory response assessment.
- Response rate benchmark for PLD: The patient population treated in this study to date is similar to the population enrolled in the Pfizer-sponsored JAVELIN Ovarian 200 clinical trial, wherein PLD monotherapy provided an overall response rate of 4%.
- SL-172154 plus PLD had an acceptable safety profile and is consistent with the safety profile of the individual agents:
- As of the data cut-off date of October 31, 2023, among the 16 treated patients, the most common SL-172154-related adverse events were infusion related reaction, nausea, fatigue, headache and neutropenia, mostly in Grade 1-2. SL-172154-related adverse events in Grade 3 or 4 were observed in 6 patients: anemia (n=2), aspartate aminotransferase increased (n=2), neutropenia (n=2), alanine aminotransferase increased (n=1), embolism (n=1) and thrombocytopenia (n=1). SL-172154-related IRRs occurred in four patients but were manageable and did not prevent the completion of dosing or lead to discontinuation. There were no Grade 5 adverse events.
- The Phase 1B combination trial in PROC of SL-172154 in combination with PLD is using the 3 mg/kg dose of SL-172154.
- Next steps and anticipated milestones:
- Completion of planned enrollment of the Phase 1B dose-expansion cohort of SL-172154 in combination with PLD in PROC expected in the fourth quarter of 2023.
Upcoming Milestones
SL-172154 (SIRPα-Fc-CD40L)
- Topline data from Phase 1A/B dose escalation clinical trial of SL-172154 in R/R AML and HR-MDS to be presented at the 65th ASH Annual Meeting.
- Initial data from the frontline TP53 mutant AML dose-expansion cohort and frontline HR-MDS dose-expansion cohort combining SL-172154 with AZA expected in the fourth quarter of 2023.
- Initial data from the ongoing Phase 1B clinical trial of SL-172154 in combination with mirvetuximab soravtansine in PROC expected mid-year 2024.
- Additional data from the ongoing Phase 1B clinical trial of SL-172154 in combination with PLD in PROC expected mid-year 2024.
Third Quarter 2023 Recent Business Highlights and Other Recent Developments
ARC Clinical-Stage Pipeline
SL-172154 (SIRPα-Fc-CD40L)
- Enrollment completed in the TP53 mutant AML dose expansion cohort of the Phase 1A/B Clinical Trial of SL-172154 in combination with AZA; enrollment in the HR-MDS cohort expected to complete in the fourth quarter: This trial is evaluating SL-172154 in combination with AZA in both frontline HR-MDS patients and frontline TP53 mutant AML patients. The data from the dose-escalation portion of the clinical trial in primarily R/R patients, which preceded the expansion cohorts in frontline patients, will be presented at the 65th ASH Annual Meeting. The abstract was made available on November 2, 2023. As of the May 25, 2023 data cut-off date used for the ASH abstract, 37 patients with R/R AML or HR-MDS had received SL-172154 as monotherapy or in combination with AZA in the parallel staggered dose-escalation portion of the clinical trial. Patients had a median of two prior lines of therapy. As of the data cut-off date of July 10, 2023 used for efficacy evaluation for the ASH abstract, a monotherapy response in a R/R AML patient and early signals of anti-leukemic activity (in the form of blast count reductions) in patients with R/R AML who received SL-172154 in combination with AZA were observed in a dose-dependent manner. Early signals of activity with SL-172154 in combination with AZA in frontline patients with TP53 mutant HR-MDS were also observed. Out of four evaluable previously untreated TP53 mutant HR-MDS patients, there was one complete response, one marrow complete response, and two stable disease. SL-172154 had an acceptable safety profile as monotherapy and in combination with AZA. Shattuck remains on track to share initial data in the fourth quarter of 2023 from the frontline expansion cohorts in TP53 mutant AML and HR-MDS.
- Continued Dosing of Patients in Phase 1B Clinical Trial of SL-172154 in Combination with Mirvetuximab Soravtansine in PROC. This trial is evaluating the safety, pharmacokinetics, pharmacodynamic effects, and preliminary anti-tumor activity of SL-172154 administered in combination with mirvetuximab soravtansine in patients with PROC. Mirvetuximab soravtansine is an antibody-drug conjugate targeting folate receptor alpha (FRα), which provides for both direct tumor cell killing as well as enhanced macrophage phagocytosis through binding with Fc gamma receptors and has received accelerated approval for PROC patients whose tumors are shown to be FRα positive, defined as ≥75%, as determined by the VENTANA FOLR1 (FOLR1-2.1) Assay. Preclinical studies have shown that both of these killing mechanisms are complementary to the mechanism of SL-172154 by enhancing the activity of macrophages to phagocytose FRα- expressing ovarian cancer cells, and that SL-172154 may broaden the activity of mirvetuximab soravtansine, particularly in patients with tumors that express lower levels of FRα. Shattuck intends to enroll patients with broader FRα expression, including those with “high” (greater than ≥75%), “medium” (≥50% to
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