HST-1011 / HotSpot Therap - LARVOL DELTA

SOLAR1: A Study of HST-1011 Given as Monotherapy and in Combination With an Anti-PD1 Antibody (clinicaltrials.gov) - P1/2 | N=77 | Active, not recruiting | Sponsor: HotSpot Therapeutics, Inc | Recruiting ➔ Active, not recruiting | N=203 ➔ 77

Enrollment change • Enrollment closed • Monotherapy • Anal Carcinoma • Colorectal Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor

Peripheral blood and tumor gene expression as biomarkers and potential predictors of clinical outcome with HST-1011, an oral CBL-B inhibitor (SITC 2024) - P1/2 | "Conclusions HST-1011 was associated with dose-dependent changes in peripheral blood pharmacodynamic measures that were sustained with repeated dosing and pre-treatment tumor WTS provided preliminary suggestion of a potential enrichment approach for a study population most likely to benefit from HST-1011. Monotherapy dose-optimization and combination with anti-PD-1 are ongoing."

Biomarker • Clinical • Clinical data • IO biomarker • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

HotSpot Therapeutics Presents Additional Phase 1 Biomarker Data on Novel CBL-B Inhibitor HST-1011 at 2024 Society for Immunotherapy of Cancer Annual Meeting (PRNewswire) - P1/2 | N=203 | NCT05662397 | Sponsor: HotSpot Therapeutics, Inc | "The presentation describes additional clinical biomarker data from the ongoing Phase 1 monotherapy dose-escalation study of HST-1011: An HST-1011-derived gene response signature showed a consistent dose-dependent increase in patient peripheral blood, with patients who demonstrated clinical benefit showing a higher expression of the signature in on-treatment biopsies. Preliminary T- and B-cell receptor next-generation sequencing data showed HST-1011 impacted both immune cell populations, with changes observed in several metrics associated with clinical benefit. At baseline, patients who benefitted from HST-1011 treatment showed higher tumor-infiltrating lymphocyte expression and a higher immune signature score, suggesting a potential for prediction of clinical benefit."

Biomarker • P1 data • Solid Tumor

HotSpot Therapeutics to Present Additional Phase 1 Biomarker Data on Novel CBL-B Inhibitor HST-1011 at 2024 Society for Immunotherapy of Cancer Annual Meeting (PRNewswire) - "HotSpot Therapeutics,...today announced it will present additional Phase 1 clinical biomarker data for HST-1011, an investigational oral, selective inhibitor of Casitas B-lineage lymphoma proto-oncogene (CBL-B), in a poster presentation at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting, taking place November 6-10, 2024, in Houston, Texas. The poster will showcase exploration of potential clinical biomarkers that correlate with signs of clinical activity in patients from the ongoing Phase 1 monotherapy dose-escalation study of HST-1011."

Biomarker • P1 data • Oncology • Solid Tumor

First-in-human (FIH) phase I data of HST-1011, an oral CBL-B inhibitor, in patients with advanced solid tumors (ESMO 2024) - P1/2 | "HST-1011 monotherapy has a manageable safety profile with correlative evidence of PK-TE-PD and early signs of single-agent activity in heavily pre-treated solid tumor patients, supporting its ongoing evaluation in dose optimization and PD-1 combination."

Clinical • IO biomarker • Metastases • P1 data • Hematological Malignancies • Lung Cancer • Lymphoma • Non Small Cell Lung Cancer • Oncology • Ovarian Cancer • Solid Tumor

Honored to present the First-in-Human Phase I Data of HST-1011, an Oral CBL-B Inhibitor, in Patients with Advanced Solid Tumors, at ESMO - European Society for Medical Oncology 2024 in Barcelona, representing Earle A. Chiles Research Institute Providence Cancer Institute. Check out Carlo Bifulco and Rom Leidner at Monday's Presidential Symposium, presenting, "Application of GigaPath: An... (LinkedIn)

HotSpot Therapeutics Presents First-in-Human Phase 1 Clinical Data on its Novel CBL-B Inhibitor, HST-1011, at ESMO Congress 2024 (PRNewswire) - P1/2 | N=203 | NCT05662397 | Sponsor: HotSpot Therapeutics, Inc | "The results being presented at ESMO 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....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."

P1 data • Solid Tumor

HotSpot Therapeutics to Present Initial First-in-Human Phase 1 Clinical Data on its Novel CBL-B Inhibitor, HST-1011, at ESMO Congress 2024 (PRNewswire) - "HotSpot Therapeutics, Inc...announced it will present initial clinical data, with a focus on safety, exposure, and pharmacodynamic measures, from the monotherapy dose-escalation portion of the Phase 1 study of HST-1011, an oral, selective inhibitor of Casitas B-lineage lymphoma proto-oncogene (CBL-B), in a Proffered Paper oral presentation at the European Society for Medical Oncology (ESMO) Congress 2024, taking place September 13-17, 2024, in Barcelona, Spain."

P1 data • Oncology • Solid Tumor

Exploring proximal biomarkers of CBL-B inhibition in human peripheral blood mononuclear cells (SITC 2023) - P1/2 | "Conclusions Evaluating the effect of CBL-Bi on TCR signaling enabled identification of a repertoire of proximal biomarkers with potential to monitor and optimize CBL-Bi clinically. We believe clinical validation and exploration are warranted to assess the utility of these proximal biomarkers and their association with downstream pharmacodynamics following treatment with HST-1011 in the clinic."

Biomarker • IO biomarker • Hematological Malignancies • Lymphoma • Oncology • CD3E • CD4 • CD8 • NOTCH1 • UBR5 • ZAP70

HotSpot Therapeutics Presents Preclinical Data from CBL-B Program at 2023 Society for Immunotherapy of Cancer Annual Meeting (PRNewswire) - "HotSpot Therapeutics, Inc...today announced the presentation of additional preclinical data from the Company's Casitas B-lineage lymphoma proto-oncogene (CBL-B) program in a poster presentation at the 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting....The presentation describes preclinical data in which HotSpot CBL-B inhibitors were evaluated in both in vitro and in vivo settings to identify and then characterize a repertoire of potential proximal biomarkers of CBL-B inhibitory activity. Several proteins, including phosphorylated ZAP70, Notch1 and IGF1R, showed robust dose-dependent effects and were further assessed for their reliability and potential feasibility for use in a clinical setting."

Preclinical • Oncology • Solid Tumor

HotSpot Therapeutics to Present Preclinical Data from CBL-B Program at 2023 Society for Immunotherapy of Cancer Annual Meeting (PRNewswire) - "HotSpot Therapeutics, Inc...announced it will present additional preclinical data from the Company's CBL-B program in a poster presentation at the 2023 Society for Immunotherapy of Cancer (SITC) Annual Meeting, taking place November 1-5, 2023, in San Diego, CA."

Preclinical • Oncology

Immunotherapies Evaluated in New Trials for AML, Melanoma and Solid Tumor Cancers - "This study has two arms of phase I, which includes dose escalation of HST-1011 alone and in combination with cemiplimab. Phase II will evaluate the efficacy of the combination of medications based on the recommended dosage learned in phase I. Rachel E. Sanborn, M.D...is the principal investigator."

Phase 1/2 study of HST-1011, an oral CBL-B inhibitor, alone and in combination with anti-PD1 in patients with advanced solid tumors (AACR 2023) - P1/2 | "Background: The E3 ligase Casitas B-lineage lymphoma proto-oncogene B (CBL-B) is a master negative regulator of the immune system and thus an attractive target to address suboptimal outcomes to immune checkpoint inhibitors (ICI). Ph1, Part B: HST-1011 dose escalation in combination with cemiplimab, as in Part A1 with a BOIN design and optional dosing cohorts.Biomarkers: Target engagement and PD will be assessed via a) serial monitoring of cytokines/chemokines and transcriptional profiles; b) peripheral immune cell profiling; and c) in-depth analysis of screening and on-treatment tumor biopsies. The study is open with competitive enrollment."

Clinical • Combination therapy • IO biomarker • Metastases • P1/2 data • Anal Carcinoma • Colorectal Cancer • Gastrointestinal Cancer • Genito-urinary Cancer • Hematological Malignancies • Lymphoma • Oncology • Ovarian Cancer • Prostate Cancer • Rectal Cancer • Solid Tumor

HotSpot Therapeutics Presents Preclinical Data from CBL-B Program at AACR Annual Meeting 2023 (PRNewswire) - "HotSpot Therapeutics...announced the presentation of additional preclinical data on the Company's casitas B-lineage lymphoma-B (CBL-B) program in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2023....Preclinical data highlighted ability of HotSpot's CBL-B inhibitors to enhance the effector function and proliferation of natural killer cells, which HotSpot believes supports the therapeutic utility of a CBL-B inhibitor....'We look forward to continuing to advance HST-1011, our lead CBL-B inhibitor clinical candidate, through our ongoing Phase 1 clinical study in patients'."

Preclinical • Oncology

HotSpot Therapeutics achieves first-in-human dosing with HST-1011, an investigational oral small molecule allosteric inhibitor of CBL-B (Pharmabiz) - "'Despite tremendous progress in the field of immuno-oncology (I-O), significant unmet need persists for patients with advanced solid tumours, as many cancers are found to be unresponsive to or lack durable responses following treatment with currently available therapies,' said Jason Luke, M.D....'We believe CBL-B's role as a master regulator of immune cell activation presents a differentiated therapeutic opportunity. We are excited to explore this novel mechanism and new I-O treatment in collaboration with HotSpot and the other investigators and sites participating in this trial.'"

Media quote

A Study of HST-1011 Given as Monotherapy and in Combination With an Anti-PD1 Antibody (clinicaltrials.gov) - P1/2 | N=203 | Recruiting | Sponsor: HotSpot Therapeutics, Inc | Not yet recruiting ➔ Recruiting

Combination therapy • Enrollment open • IO biomarker • Metastases • Monotherapy • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Ovarian Cancer • Prostate Cancer • Solid Tumor

HotSpot Therapeutics Achieves First-In-Human Dosing with HST-1011, An Investigational Oral Small Molecule Allosteric Inhibitor of CBL-B (PRNewswire) - "HotSpot Therapeutics, Inc...announced the recent initiation of dosing of HST-1011 in its Phase 1/2 clinical trial in patients with advanced solid tumors....The Phase 1/2 study of HST-1011 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 patients with advanced solid tumors that are relapsed on or are refractory to anti-PD(L)-1 or standard of care therapies....HotSpot will be presenting the HST-1011 first-in-human Phase 1/2 clinical trial design at the upcoming American Association for Cancer Research (AACR) Annual Meeting 2023, taking place in Orlando, Florida, during the Clinical Trials in Progress poster session."

Clinical protocol • Trial status • Oncology • Solid Tumor

HotSpot Therapeutics to Present Two Poster Presentations on CBL-B Program at AACR Annual Meeting 2023 (PRNewswire) - "HotSpot Therapeutics...announced it will present two poster presentations on the company's CBL-B program at the American Association for Cancer Research (AACR) Annual Meeting 2023, taking place April 14-19, 2023, in Orlando, FL. One poster will describe preclinical data for the CBL-B program, and one Clinical Trials in Progress poster will describe the first-in-human Phase 1/2 clinical trial of HST-1011."

Preclinical • Trial status • Oncology • Solid Tumor

"#HotSpotTherapeutics Announces #FDA Clearance of #INDApplication for #HST1011, An Investigational #SmallMolecule #AllostericInhibitor of #CBLB https://t.co/zslxb6mmsj" (@1stOncology)

FDA event

HotSpot Therapeutics Announces FDA Clearance of IND Application for HST-1011, An Investigational Small Molecule Allosteric Inhibitor of CBL-B (PRNewswire) - "HotSpot Therapeutics, Inc....announced the clearance by the U.S. Food and Drug Administration (FDA) of the Investigational New Drug (IND) application for HST-1011, the Company's investigational small molecule allosteric inhibitor of casitas B-lineage lymphoma-B (CBL-B). This represents the first IND filing for HotSpot. The Company expects to initiate the Phase 1/2 study of HST-1011 in the first quarter of 2023, with an initial focus on the evaluation of HST-1011 as monotherapy in patients with advanced solid tumors who are relapsed or refractory to anti-PD(L)1 therapy"."

IND • Trial status • Hematological Malignancies • Lymphoma • Oncology • Solid Tumor

A Study of HST-1011 Given as Monotherapy and in Combination With an Anti-PD1 Antibody (clinicaltrials.gov) - P1/2 | N=203 | Not yet recruiting | Sponsor: HotSpot Therapeutics, Inc

New P1/2 trial • Colorectal Cancer • Gastrointestinal Cancer • Oncology • Prostate Cancer • Solid Tumor

HotSpot Therapeutics Presents Preclinical Data from CBL-B Program at 2022 Society for Immunotherapy of Cancer Annual Meeting (PRNewswire) - "The presentations describe compelling data for HotSpot compounds designed as novel, allosteric, small molecule inhibitors of CBL-B E3 ubiquitin ligase activity: A HotSpot CBL-B inhibitor demonstrated immune-mediated tumor growth inhibition in multiple syngeneic mouse models. Gene expression profiling of the tumor microenvironment demonstrated upregulation of pro-inflammatory pathways in vivo. These effects were notable with CBL-B inhibition alone and further enhanced when combined with a PD-1 inhibitor. In the MLR assay, a predictive correlate of the clinical activity of I-O therapies, the HotSpot CBL-B inhibitor demonstrated robust effects on cytokine release and T cell proliferation as monotherapy. Additionally, CBL-B inhibition demonstrated synergistic activity in the MLR assay when combined with anti-PD1."

Preclinical • Oncology

HotSpot Therapeutics Presents Pre-Clinical Data on CBL-B Program at American Association for Cancer Research Annual Meeting 2022 (PRNewswire) - "HotSpot Therapeutics...announced the presentation of additional pre-clinical data on the Company's Casitas B-lineage lymphoma proto-oncogene (CBL-B) program in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2022....When added to exhausted T cell cultures or to effector T cells in the presence of regulatory T cells in vitro, the HotSpot CBL-B inhibitor demonstrated an ability to reduce the effects of suppressive mechanisms."

Preclinical • Oncology

HotSpot Therapeutics to Present Pre-Clinical Data on CBL-B Program at American Association for Cancer Research Annual Meeting 2022 (PRNewswire) - "HotSpot Therapeutics...announced it will present additional pre-clinical data on the company's CBL-B program in a poster presentation at the American Association for Cancer Research (AACR) Annual Meeting 2022, taking place April 8-13, 2022, in New Orleans, LA."

Preclinical • Oncology