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

NCT05662397 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: Clin-001
• Study Type: interventional
• Target: 77
• Locations: 3 countries
• Sites: 14

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.

Conditions

Solid Tumor, Adult; Relapsed Cancer; Refractory Cancer

Keywords

CBL-B; anti-PD-(L)1

Outcome Measures

Primary Outcomes (2)

• 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.

  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.

  12 months

Secondary Outcomes (10)

• Evaluate the safety and tolerability of single-agent HST-1011 in Part A2.

  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.

  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.

  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.

  12 months

• Evaluate intratumoral gene expression changes of single-agent HST-1011 in Part A2 and in combination with cemiplimab in Part B2.

  12 months

Study Arms (4)

HST-1011 Monotherapy Dose Escalation (Part A1)

EXPERIMENTAL

Multiple dose levels of HST-1011 to be evaluated.

Drug: HST-1011

HST-1011 Monotherapy Dose Optimization (Part A2)

EXPERIMENTAL

Evaluation of HST-1011 monotherapy dose/dose regimen.

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.

Drug: HST-1011; Biological: Cemiplimab

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

EXPERIMENTAL

Evaluation of HST-1011 in combination with cemiplimab.

Drug: HST-1011; Biological: Cemiplimab

Interventions

HST-1011 DRUG

HST-1011 given orally

Also known as: CBL-B inhibitor

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)

Cemiplimab BIOLOGICAL

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

Also known as: anti-PD1 antibody

HST-1011 Dose Escalation in Combination with cemiplimab (Part B1); HST-1011 Dose Optimization in Combination with Cemiplimab (Part B2)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• HotSpot Therapeutics, Inc: lead

Study Sites (14)

Florida Cancer Specialists

Sarasota, Florida, 34232, United States

Location

Comprehensive Cancer Centers of Nevada

Las Vegas, Nevada, 89169, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10087, United States

Location

Montefiore Einstein Comprehensive Cancer Center

The Bronx, New York, 10461, United States

Location

Providence Cancer Institute of Oregon

Portland, Oregon, 97213, United States

Location

Abramson Cancer Center

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh (UPMC), Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

The University of Texas MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

University of Ottawa

Ottawa, Ontario, K1N 6N5, Canada

Location

Princess Margaret Cancer Center

Toronto, Ontario, M5G 2M9, Canada

Location

NEXT Oncology Barcelona IOB Hospital Quirónsalud

Barcelona, Spain

Location

Clínica Universidad de Navarra

Madrid, Spain

Location

NEXT Oncology Hospital Universitario Quirónsalud Madrid

Madrid, Spain

Location

Clínica Universidad de Navarra (Pamplona)

Pamplona, Spain

Location

MeSH Terms

Conditions

Recurrence; Neoplasms

Interventions

cemiplimab; spartalizumab

Condition Hierarchy (Ancestors)

Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alison O'Neill, MD

  HotSpot Therapeutics, Inc

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 2, 2022
• First Posted: December 22, 2022
• Study Start: March 15, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: February 4, 2025

Record last verified: 2025-02

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); US (8); ES (4)