Refractory Cancer, Relapsed Cancer, Solid Tumor, Adult
Conditions
Keywords
CBL-B, anti-PD-(L)1
Brief 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.
Detailed 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 B1 and B2). Part A1 is a monotherapy dose escalation in which cohorts of patients will receive increasing doses of HST-1011. Upon completion of Part A1 dose escalation, an HST-1011 monotherapy dose optimization will commence (Part A2). Part B1 is a dose escalation of HST-1011 given in combination with the standard dose/regimen of cemiplimab. Dosing in Part B1 may commence prior to the completion of Part A1. Upon completion of Part B1 dose escalation, an HST-1011 dose optimization in combination with cemiplimab will commence (Part B2). 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.
Interventions
DRUGHST-1011
HST-1011 given orally
BIOLOGICALCemiplimab
Cemiplimab administered via intravenous infusion in combination with HST-1011 given orally
Sponsors
HotSpot Therapeutics, Inc
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| To determine the Recommended Phase 2 Dose (RP2D) and schedule of HST-1011 monotherapy in Part A2 and in combination with cemiplimab in Part B2. | 12 months | Integration of safety, PD, PK, and preliminary efficacy endpoints. |
| Evaluate the safety and tolerability of escalating doses of single-agent HST-1011 in Part A1 or in combination with cemiplimab in Part B1. | 12 months | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Characterize the concentration of peripheral blood cytokines/chemokines following HST-1011 monotherapy Part A1 and Part A2, or in combination with cemiplimab in Part B1. | 12 months | Measure of peripheral pharmacodynamic (PD) markers after oral administration of HST-1011 or combination of orally administered HST-1011 and IV infused cemiplimab. |
| Characterize global gene expression profiles following HST-1011 monotherapy Part A1 and Part A2, or in combination with cemiplimab in Part B1 and Part B2. | 12 months | Measure of peripheral pharmacodynamic (PD) markers after oral administration of HST-1011 or combination of orally administered HST-1011 and IV infused cemiplimab. |
| Evaluate intratumoral gene expression changes of single-agent HST-1011 in Part A2 and in combination with cemiplimab in Part B2. | 12 months | Measure of intratumoral pharmacodynamic (PD) markers after oral administration of HST-1011 alone and in combination with cemplimab. |
| Overall Response Rate (ORR) following HST-1011 monotherapy Part A1 and Part A2, or in combination with cemiplimab in Part B1 and Part B2. | 12 months | 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. |
| Evaluate the safety and tolerability of single-agent HST-1011 in Part A2. | 12 months | 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. |
| Disease Control Rate (DCR) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2. | 12 months | 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. |
| Progression Free Survival (PFS) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2. | 12 months | Defined as the time from first treatment to first occurrence of progressive disease or death from any cause. |
| Overall Survival (OS) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B. | 12 months | Defined as the time from first treatment to death from any cause. |
| Duration of response (DOR) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2. | 12 months | 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. |
| 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. | 12 months | 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. |
Countries
Canada, Spain, United States
Outcome results
None listed