Solid Tumor, AdultPhase 1/2NCT05662397
A Study of HST-1011 Given as Monotherapy and in Combination With an Anti-PD1 Antibody
A Phase 1/2 study testing HST-1011 and Cemiplimab in people with Solid Tumor, Adult and Relapsed Cancer, run by HotSpot Therapeutics, Inc at 14 sites in 3 countries.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Solid Tumor, Adult, Relapsed Cancer, Refractory Cancer
- What is being tested?
- HST-1011 and Cemiplimab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 77 participants
- Where
- 14 sitesin 3 countries
- Study dates
- 15 Mar 2023to 31 Dec 2026
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
14 sites in 3 countries.
14 sites in 3 countries
United States8 sites
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Comprehensive Cancer Centers of Nevada
Las Vegas, Nevada, 89169
Memorial Sloan Kettering Cancer Center
New York, New York, 10087
Abramson Cancer Center
Philadelphia, Pennsylvania, 19104
University of Pittsburgh (UPMC), Hillman Cancer Center
Pittsburgh, Pennsylvania, 15232
Providence Cancer Institute of Oregon
Portland, Oregon, 97213
Florida Cancer Specialists
Sarasota, Florida, 34232
Montefiore Einstein Comprehensive Cancer Center
The Bronx, New York, 10461
Spain4 sites
NEXT Oncology Barcelona IOB Hospital Quirónsalud
Barcelona
Clínica Universidad de Navarra
Madrid
NEXT Oncology Hospital Universitario Quirónsalud Madrid
Madrid
Clínica Universidad de Navarra (Pamplona)
Pamplona
Canada2 sites
University of Ottawa
Ottawa, Ontario, K1N 6N5
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9
About this study
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.
Read the 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.
- Conditions
- Solid Tumor, Adult, Relapsed Cancer, Refractory Cancer
- Being tested
- HST-1011, Cemiplimab
- Keywords
- CBL-B, anti-PD-(L)1
- Medical subject headings
- Recurrence, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HST-1011Drug
Also called CBL-B inhibitor
HST-1011 given orally
CemiplimabBiological
Also called anti-PD1 antibody
Cemiplimab administered via intravenous infusion in combination with HST-1011 given orally
| Study group | Role | What they receive |
|---|---|---|
| HST-1011 Monotherapy Dose Escalation (Part A1) | Experimental | Multiple dose levels of HST-1011 to be evaluated. Receives: Drug: HST-1011 |
| HST-1011 Monotherapy Dose Optimization (Part A2) | Experimental | Evaluation of HST-1011 monotherapy dose/dose regimen. Receives: Drug: HST-1011 |
| HST-1011 Dose Escalation in Combination with cemiplimab (Part B1) | Experimental | Multiple dose levels of HST-1011 to be evaluated in combination with cemiplimab. Receives: Drug: HST-1011; Biological: Cemiplimab |
| HST-1011 Dose Optimization in Combination with Cemiplimab (Part B2) | Experimental | Evaluation of HST-1011 in combination with cemiplimab. Receives: Drug: HST-1011; Biological: Cemiplimab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Evaluate the safety and tolerability of escalating doses of single-agent HST-1011 in Part A1 or in combination with cemiplimab in Part B1.
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.
Measured: 12 months
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.
Integration of safety, PD, PK, and preliminary efficacy endpoints.
Measured: 12 months
Secondary outcomes (10)
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.
Measured: 12 months
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.
Measured: 12 months
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.
Measure of peripheral pharmacodynamic (PD) markers after oral administration of HST-1011 or combination of orally administered HST-1011 and IV infused cemiplimab.
Measured: 12 months
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.
Measure of peripheral pharmacodynamic (PD) markers after oral administration of HST-1011 or combination of orally administered HST-1011 and IV infused cemiplimab.
Measured: 12 months
Evaluate intratumoral gene expression changes of single-agent HST-1011 in Part A2 and in combination with cemiplimab in Part B2.
Measure of intratumoral pharmacodynamic (PD) markers after oral administration of HST-1011 alone and in combination with cemplimab.
Measured: 12 months
Overall Response Rate (ORR) following HST-1011 monotherapy Part A1 and Part A2, or in combination with cemiplimab in Part B1 and Part B2.
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.
Measured: 12 months
Duration of response (DOR) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2.
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.
Measured: 12 months
Disease Control Rate (DCR) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2.
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.
Measured: 12 months
Progression Free Survival (PFS) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2.
Defined as the time from first treatment to first occurrence of progressive disease or death from any cause.
Measured: 12 months
Overall Survival (OS) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B.
Defined as the time from first treatment to death from any cause.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Dec 2022
- Study start15 Mar 2023
- Primary completion31 Dec 2025 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Solid Tumor, AdultStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Enrolment
- 77 participants (actual)
Sponsor and investigators
- Lead sponsor
- HotSpot Therapeutics, Inc
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Alison O'Neill, MD, Study director, HotSpot Therapeutics, Inc
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05662397
- Sponsor's protocol ID
- Clin-001
- Status last verified
- Feb 2025
- First submitted
- 2 Dec 2022
- Last updated
- 4 Feb 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT05662397
- Acronym / sponsor ID
- Clin-001
- Conditions
- Solid Tumor, Adult, Relapsed Cancer, Refractory Cancer
- Keywords
- CBL-B, anti-PD-(L)1
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 77 participants (actual)
- Lead sponsor
- HotSpot Therapeutics, IncIndustry (pharma, biotech, devices)
- Study start
- 15 Mar 2023 (actual)
- Primary completion
- 31 Dec 2025 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 22 Dec 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| HST-1011 Monotherapy Dose Escalation (Part A1) | Experimental | Drug: HST-1011Multiple dose levels of HST-1011 to be evaluated. |
| HST-1011 Monotherapy Dose Optimization (Part A2) | Experimental | Drug: HST-1011Evaluation of HST-1011 monotherapy dose/dose regimen. |
| HST-1011 Dose Escalation in Combination with cemiplimab (Part B1) | Experimental | Drug: HST-1011, Biological: CemiplimabMultiple dose levels of HST-1011 to be evaluated in combination with cemiplimab. |
| HST-1011 Dose Optimization in Combination with Cemiplimab (Part B2) | Experimental | Drug: HST-1011, Biological: CemiplimabEvaluation of HST-1011 in combination with cemiplimab. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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.
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HST-1011Also: CBL-B inhibitorHST-1011 given orally | Drug | HST-1011 Dose Escalation in Combination with cemiplimab (Part B1), HST-1011 Dose Optimization in Combination with Cemiplimab (Part B2), HST-1011 Monotherapy Dose Escalation (Part A1), HST-1011 Monotherapy Dose Optimization (Part A2) |
| CemiplimabAlso: anti-PD1 antibodyCemiplimab administered via intravenous infusion in combination with HST-1011 given orally | Biological | HST-1011 Dose Escalation in Combination with cemiplimab (Part B1), HST-1011 Dose Optimization in Combination with Cemiplimab (Part B2) |
Primary outcome
Evaluate the safety and tolerability of escalating doses of single-agent HST-1011 in Part A1 or in combination with cemiplimab in Part B1.
Time frame: 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.
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.
Time frame: 12 months
Integration of safety, PD, PK, and preliminary efficacy endpoints.
10 secondary outcomes
Evaluate the safety and tolerability of single-agent HST-1011 in Part A2.
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
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.
Time frame: 12 months
Evaluate intratumoral gene expression changes of single-agent HST-1011 in Part A2 and in combination with cemiplimab in Part B2.
Time frame: 12 months
Overall Response Rate (ORR) following HST-1011 monotherapy Part A1 and Part A2, or in combination with cemiplimab in Part B1 and Part B2.
Time frame: 12 months
Duration of response (DOR) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2.
Time frame: 12 months
Disease Control Rate (DCR) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2.
Time frame: 12 months
Progression Free Survival (PFS) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2.
Time frame: 12 months
Overall Survival (OS) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B.
Time frame: 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Feb 2025.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Alison O'Neill, MD study director
HotSpot Therapeutics, Inc
14 sites in 3 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing HST-1011 and Cemiplimab in people with Solid Tumor, Adult and Relapsed Cancer, run by HotSpot Therapeutics, Inc at 14 sites in 3 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 4 Feb 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 14 sites in United States, Spain, Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Evaluate the safety and tolerability of escalating doses of single-agent HST-1011 in Part A1 or in combination with cemiplimab in Part B1. (time frame: 12 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Feb 2025.