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
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.
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. |
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 |
Lead Sponsor | Collaborator |
---|---|
HotSpot Therapeutics, Inc |
United States,
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 |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
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