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.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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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

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.

Country

City, postcode or hospital

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

Other trials in United States

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

Other trials in Spain

Canada2 sites

University of Ottawa
Ottawa, Ontario, K1N 6N5
Princess Margaret Cancer Center
Toronto, Ontario, M5G 2M9

Other trials in Canada

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

Read the detailed description

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 groups in NCT05662397
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.

15 Mar 202331 Dec 2026

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)

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

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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