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

HotSpot Therapeutics

Status and phase: Enrolling; Phase 2; Phase 1

Conditions: Relapsed Cancer; Solid Tumor, Adult; Refractory Cancer

Treatments: Biological: Cemiplimab; Drug: HST-1011

Study type: Interventional

Funder types: Industry

Identifiers

NCT05662397

Clin-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 203 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion 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.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

---

203 participants in 4 patient groups

HST-1011 Monotherapy Dose Escalation (Part A1)

Experimental group

Description:

Multiple dose levels of HST-1011 to be evaluated.

Treatment:

Drug: HST-1011

HST-1011 Monotherapy Dose Optimization (Part A2)

Experimental group

Description:

Evaluation of HST-1011 monotherapy dose/dose regimen.

Treatment:

Drug: HST-1011

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

Experimental group

Description:

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

Treatment:

Drug: HST-1011

Biological: Cemiplimab

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

Experimental group

Description:

Evaluation of HST-1011 in combination with cemiplimab.

Treatment:

Drug: HST-1011

Biological: Cemiplimab