On September 12, 2024 HotSpot Therapeutics, Inc., a biotechnology company pioneering the discovery and development of oral, small molecule allosteric therapies targeting regulatory sites on proteins referred to as "natural hotspots," reported the presentation of initial clinical data for HST-1011, an investigational oral, selective inhibitor of Casitas B-lineage lymphoma proto-oncogene (CBL-B) (Press release, HotSpot Therapeutics, SEP 12, 2024, View Source [SID1234646542]). Data from the Phase 1 monotherapy dose escalation portion of the study are being shared in a proffered oral presentation at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2024.

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"These initial data provide the first comprehensive insight into the clinical experience with a CBL-B inhibitor, a novel immuno-oncology mechanism with the potential to meaningfully transform the treatment paradigm for patients with solid tumors," said Timothy Reilly, Ph.D., Chief Development Officer of HotSpot. "Critically, HST-1011 demonstrated important linkages between drug exposures, target engagement, and proximal and distal measures of pharmacology, and we observed initial signs of clinical benefit, in a heavily pre-treated, advanced solid tumor patient population. We believe these data provide a strong foundation for the continued evaluation of HST-1011 in dedicated patient populations and for the further assessment of HST-1011 in combination with a PD-1 inhibitor, cemiplimab."

The Phase 1/2 study of HST-1011 (NCT05662397) is an open-label clinical study designed to evaluate HST-1011 alone and subsequently in combination with Regeneron’s anti-PD-1 therapy, Libtayo (cemiplimab), in adult patients with advanced solid tumors that are relapsed on or are refractory to anti-PD(L)-1 or standard of care therapies. The results being presented at ESMO (Free ESMO Whitepaper) include data from 28 patients in the monotherapy dose escalation portion of the study. The presentation describes the following data:

Patients had a diverse range of solid tumor types and were heavily pre-treated, with a median of four prior lines of therapy, including 89% who had been treated previously with immunotherapy.
HST-1011 was generally well tolerated across a range of twice-weekly doses, with no dose-limiting toxicities. The most frequent adverse events were gastrointestinal in nature, which were generally mitigated by the adoption of a prophylactic pre-treatment regimen.
Encouraging linkages were observed between pharmacokinetics (PK), target engagement, pharmacodynamics (PD) and initial signals of clinical activity. Despite the heavily pre-treated, advanced cancer patient population, indications of clinical benefit, including tumor stasis or shrinkage, were observed in 10 of the 28 patients across a range of tumor types and dose levels.
These encouraging data provide support for the ongoing evaluation of HST-1011 (NCT05662397).

Presentation details are as follows:

Title: First-in-Human (FIH) Phase 1 Data of HST-1011, an Oral CBL-B Inhibitor, in Patients with Advanced Solid Tumors
Speaker: Rachel E. Sanborn, M.D., Earle A. Chiles Research Institute, Providence Cancer Institute, Portland, OR
Session Name: Proffered Paper session: Investigational immunotherapy
Session Date and Time: Fri., Sep. 13, 2024, 16:00-17:30 CEST
Presentation Time: 16:50-17:00 CEST
Location: Burgos Auditorium – Hall 5, Fira Barcelona Gran Via
Presentation Number: 991O