A Study of HST-1011 Given as Monotherapy and in Combination With an Anti-PD1 Antibody

Solid Tumor, Adult Clinical Trial

Official title:

An Open Label, Phase 1/2 Study of HST-1011 Given as Monotherapy and in Combination With an Anti-PD1 Antibody in Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05662397
• Other study ID #: Clin-001
• Status: Recruiting
• Phase: Phase 1/Phase 2
• 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
• 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.

Related Conditions & MeSH terms

• Refractory Cancer
• Relapsed Cancer
• Solid Tumor, Adult

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