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Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT05662397
Other study ID # Clin-001
Secondary ID
Status Recruiting
Phase Phase 1/Phase 2
First received
Last updated
Start date March 15, 2023
Est. completion date December 31, 2026

Study information

Verified date January 2024
Source HotSpot Therapeutics, Inc
Contact HotSpot Therapeutics
Phone +1 (617) 758-8998
Email Clin001_Information@hotspotthera.com
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

This is a Phase 1/2 study of HST-1011, a CBL-B inhibitor, being developed for the treatment of patients with advanced solid tumors, who relapsed while on or are refractory to approved anti-PD(L)1 therapies or other standard of care.


Description:

This is a Phase 1/2 study of HST-1011, a CBL-B inhibitor, being developed for the treatment of patients with advanced solid tumors, who relapsed while on or are refractory to approved anti-PD(L)1 therapies or other standard of care. In Phase 1 patients will receive HST-1011 as either monotherapy (Parts A1 and A2) or in combination with the anti-PD1 antibody, cemiplimab (Part B). Part A1 is a monotherapy dose escalation in which cohorts of patients will receive increasing doses of HST-1011. Upon completion of Part A1, an HST-1011 monotherapy dose optimization will commence (Part A2). Part B is a dose escalation of HST-1011 given in combination with the standard dose/regimen of cemiplimab. Dosing in Part B may commence prior to the completion of Part A1. Phase 2 will evaluate the preliminary antitumor activity of HST-1011 in combination with anti-PD(L)1 antibody or other standard of care therapies.


Recruitment information / eligibility

Status Recruiting
Enrollment 203
Est. completion date December 31, 2026
Est. primary completion date December 31, 2025
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Key Inclusion Criteria: - Patient is at least 18 years of age. - Patient is capable of understanding and complying with protocol requirements. - Patient has signed and dated ICF. - Patient has a histologically confirmed, advanced solid tumor (metastatic, recurrent, and/or unresectable) in one of the following categories: 1) anti-PD-(L)1 relapsed/refractory; 2) platinum-resistant ovarian cancer; 4) anal cancer; 5) rectal cancer; or 6) castration-resistant prostate cancer - Patient has failed prior standard of care therapies appropriate for their metastatic disease. - Patient has at least 1 measurable non-central nervous system (CNS) lesions per RECIST 1.1. - Patient has provided consent for pre- and on-treatment biopsies. - Eastern Cooperative Performance Status of 0 or 1. Key Exclusion Criteria: - Patient has active autoimmune disease or other medical conditions requiring chronic systemic steroid therapy at the time of screening. - Patient has an unacceptable intolerance to anti-PD(L)1 monoclonal antibody (Part B Only). - Patient has previously participated in a clinical study evaluating a CBL-B inhibitor. - Patients has untreated and/or symptomatic metastatic CNS disease. - Patient is currently taking any concomitant medications at Screening that have the potential to cause a clinically relevant drug-drug interaction with HST-1011. - Patients with a history of gastrointestinal disease that may affect absorption of the study drug, or patients who are not able to take oral medications. - Patient has an active infection requiring systemic therapy. - Patient has known or suspected infection with SARS-CoV-2 virus.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
HST-1011
Increasing doses of HST-1011 given orally as monotherapy.
Biological:
Cemiplimab
Cemiplimab administered via intravenous infusion in combination with increasing doses of HST-1011 given orally as monotherapy.

Locations

Country Name City State
United States Montefiore Einstein Comprehensive Cancer Center Bronx New York
United States The University of Texas MD Anderson Cancer Center Houston Texas
United States Comprehensive Cancer Centers of Nevada Las Vegas Nevada
United States Memorial Sloan Kettering Cancer Center New York New York
United States Abramson Cancer Center Philadelphia Pennsylvania
United States University of Pittsburgh (UPMC), Hillman Cancer Center Pittsburgh Pennsylvania
United States Providence Cancer Institute of Oregon Portland Oregon
United States Florida Cancer Specialists Sarasota Florida

Sponsors (1)

Lead Sponsor Collaborator
HotSpot Therapeutics, Inc

Country where clinical trial is conducted

United States, 

Outcome

Type Measure Description Time frame Safety issue
Primary Evaluate the safety and tolerability of escalating doses of single-agent HST-1011 in Part A1 or in combination with cemiplimab in Part B. Number of participants with DLTs, with Adverse Events (TEAEs, SAEs), with abnormal clinically significant vital signs, Electrocardiograms (ECGs), with abnormal physical examination findings, and abnormal laboratory test results. 12 months
Primary Determine the Recommended Phase 2 Dose (RP2D) and schedule of HST-1011 monotherapy in Part A2. Integration of safety, PD, PK, and preliminary efficacy endpoints. 12 months
Secondary Evaluate the safety and tolerability of single-agent HST-1011 in Part A2. Number of participants with Adverse Events (TEAEs, SAEs), with abnormal clinically significant vital signs, Electrocardiograms (ECGs), with abnormal physical examination findings and abnormal laboratory test results. 12 months
Secondary Measurement of plasma concentrations of HST-1011 after monotherapy in Part A1 and Part A2 or in combination with cemiplimab in Part B to derive summary pharmacokinetic (PK) parameters including Tmax, Cmax, AUC0-last, Ctrough. Characterize pharmacokinetic parameters including Tmax, Cmax, AUC0-last, Ctrough after oral administration of HST-1011 or combination of orally administered HST-1011 and IV infused cemiplimab. 12 months
Secondary Characterize the concentration of peripheral blood cytokines/chemokines following HST-1011 monotherapy Part A1 and Part A2, or in combination with cemiplimab in Part B. Measure of peripheral pharmacodynamic (PD) markers after oral administration of HST-1011 or combination of orally administered HST-1011 and IV infused cemiplimab. 12 months
Secondary Characterize global gene expression profiles following HST-1011 monotherapy Part A1 and Part A2, or in combination with cemiplimab in Part B. Measure of peripheral pharmacodynamic (PD) markers after oral administration of HST-1011 or combination of orally administered HST-1011 and IV infused cemiplimab. 12 months
Secondary Evaluate intratumoral immune cells (number and phenotype) in tumor tissue of single-agent HST-1011 in Part A2. Measure of intratumoral pharmacodynamic (PD) markers after oral administration of HST-1011. 12 months
Secondary Evaluate intratumoral gene expression changes of single-agent HST-1011 in Part A2. Measure of intratumoral pharmacodynamic (PD) markers after oral administration of HST-1011. 12 months
Secondary Overall Response Rate (ORR) following HST-1011 monotherapy Part A1 and Part A2, or in combination with cemiplimab in Part B. Defined as the percentage of subjects who have a complete response (CR) or partial response (PR), as determined according to RECIST v1.1, or to PCWG for CRPC, if applicable. 12 months
Secondary Duration of response (DOR) of single-agent HST-1011 in Part A2. Defined as the time from when the criteria for RECIST 1.1, or to PCWG for CRPC, if applicable, CR or PR (whichever is recorded first) was first met until the date when progressive disease is documented. 12 months
Secondary Disease Control Rate (DCR) of single-agent HST-1011 in Part A2. Defined as the percentage of subjects who have a CR or PR or stable disease (SD), as determined according to RECIST v1.1, or to PCWG for CRPC, if applicable. 12 months
Secondary Progression Free Survival (PFS) of single-agent HST-1011 in Part A2. Defined as the time from first treatment to first occurrence of progressive disease or death from any cause. 12 months
Secondary Overall Survival (OS) of single-agent HST-1011 in Part A2. Defined as the time from first treatment to death from any cause. 12 months
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