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

NCT ID: NCT05662397

Last Updated: 2025-02-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

PHASE1/PHASE2

Total Enrollment

77 participants

Study Classification

INTERVENTIONAL

Study Start Date

2023-03-15

Study Completion Date

2026-12-31

Brief Summary

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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

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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

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Solid Tumor, Adult Relapsed Cancer Refractory Cancer

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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HST-1011 Monotherapy Dose Escalation (Part A1)

Multiple dose levels of HST-1011 to be evaluated.

Group Type EXPERIMENTAL

HST-1011

Intervention Type DRUG

HST-1011 given orally

HST-1011 Monotherapy Dose Optimization (Part A2)

Evaluation of HST-1011 monotherapy dose/dose regimen.

Group Type EXPERIMENTAL

HST-1011

Intervention Type DRUG

HST-1011 given orally

HST-1011 Dose Escalation in Combination with cemiplimab (Part B1)

Multiple dose levels of HST-1011 to be evaluated in combination with cemiplimab.

Group Type EXPERIMENTAL

HST-1011

Intervention Type DRUG

HST-1011 given orally

Cemiplimab

Intervention Type BIOLOGICAL

Cemiplimab administered via intravenous infusion in combination with HST-1011 given orally

HST-1011 Dose Optimization in Combination with Cemiplimab (Part B2)

Evaluation of HST-1011 in combination with cemiplimab.

Group Type EXPERIMENTAL

HST-1011

Intervention Type DRUG

HST-1011 given orally

Cemiplimab

Intervention Type BIOLOGICAL

Cemiplimab administered via intravenous infusion in combination with HST-1011 given orally

Interventions

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HST-1011

HST-1011 given orally

Intervention Type DRUG

Cemiplimab

Cemiplimab administered via intravenous infusion in combination with HST-1011 given orally

Intervention Type BIOLOGICAL

Other Intervention Names

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CBL-B inhibitor anti-PD1 antibody

Eligibility Criteria

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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.

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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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HotSpot Therapeutics, Inc

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Alison O'Neill, MD

Role: STUDY_DIRECTOR

HotSpot Therapeutics, Inc

Locations

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Florida Cancer Specialists

Sarasota, Florida, United States

Site Status

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, United States

Site Status

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Site Status

Montefiore Einstein Comprehensive Cancer Center

The Bronx, New York, United States

Site Status

Providence Cancer Institute of Oregon

Portland, Oregon, United States

Site Status

Abramson Cancer Center

Philadelphia, Pennsylvania, United States

Site Status

University of Pittsburgh (UPMC), Hillman Cancer Center

Pittsburgh, Pennsylvania, United States

Site Status

The University of Texas MD Anderson Cancer Center

Houston, Texas, United States

Site Status

University of Ottawa

Ottawa, Ontario, Canada

Site Status

Princess Margaret Cancer Center

Toronto, Ontario, Canada

Site Status

NEXT Oncology Barcelona IOB Hospital Quirónsalud

Barcelona, , Spain

Site Status

Clínica Universidad de Navarra

Madrid, , Spain

Site Status

NEXT Oncology Hospital Universitario Quirónsalud Madrid

Madrid, , Spain

Site Status

Clínica Universidad de Navarra (Pamplona)

Pamplona, , Spain

Site Status

Countries

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United States Canada Spain

Other Identifiers

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Clin-001

Identifier Type: -

Identifier Source: org_study_id

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