Clinical trial NCT05662397: A Study of HST-1011 Given as Monotherapy and in Combination With an Anti-PD1 Antibody
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
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: Solid Tumor, Adult
Relapsed Cancer
Refractory Cancer
Keywords: CBL-B
anti-PD-(L)1
Lead sponsor: HotSpot Therapeutics, Inc
Sponsor class: INDUSTRY
First posted: 2022-12-22
Enrollment: 77
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

Eligibility 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.

Primary outcomes:
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.
timeFrame: 12 months
measure: 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.
timeFrame: 12 months
Secondary outcomes:
measure: Evaluate the safety and tolerability of single-agent HST-1011 in Part A2.
timeFrame: 12 months
measure: 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.
timeFrame: 12 months
measure: 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.
timeFrame: 12 months
measure: 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.
timeFrame: 12 months
measure: Evaluate intratumoral gene expression changes of single-agent HST-1011 in Part A2 and in combination with cemiplimab in Part B2.
timeFrame: 12 months
measure: Overall Response Rate (ORR) following HST-1011 monotherapy Part A1 and Part A2, or in combination with cemiplimab in Part B1 and Part B2.
timeFrame: 12 months
measure: Duration of response (DOR) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2.
timeFrame: 12 months
measure: Disease Control Rate (DCR) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2.
timeFrame: 12 months
measure: Progression Free Survival (PFS) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B2.
timeFrame: 12 months
measure: Overall Survival (OS) of single-agent HST-1011 in Part A2, or in combination with cemiplimab in Part B.
timeFrame: 12 months
Other outcomes:
Locations:
city: Sarasota
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Las Vegas
country: United States
facility: Comprehensive Cancer Centers of Nevada
state: Nevada
city: Bronx
country: United States
facility: Montefiore Einstein Comprehensive Cancer Center
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Portland
country: United States
facility: Providence Cancer Institute of Oregon
state: Oregon
city: Philadelphia
country: United States
facility: Abramson Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh (UPMC), Hillman Cancer Center
state: Pennsylvania
city: Houston
country: United States
facility: The University of Texas MD Anderson Cancer Center
state: Texas
city: Ottawa
country: Canada
facility: University of Ottawa
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Center
state: Ontario
city: Barcelona
country: Spain
facility: NEXT Oncology Barcelona IOB Hospital Quirónsalud
city: Madrid
country: Spain
facility: Clínica Universidad de Navarra
city: Madrid
country: Spain
facility: NEXT Oncology Hospital Universitario Quirónsalud Madrid
city: Pamplona
country: Spain
facility: Clínica Universidad de Navarra (Pamplona)
Study officials:
affiliation: HotSpot Therapeutics, Inc
name: Alison O'Neill, MD
role: STUDY_DIRECTOR
References: