Clinical trial NCT05322408: HCW9218 in Select Advanced Solid Tumors
Official title: A Phase I Study of HCW9218, a Bifunctional TGF-B; Antagonist/IL-15 Protein Complex, in Select Advanced Solid Tumors After Failing at Least Two Prior Therapies
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
Conditions: Solid Tumor
Lead sponsor: Masonic Cancer Center, University of Minnesota
Sponsor class: OTHER
First posted: 2022-04-11
Enrollment: 18
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: This is a single center, Phase I dose finding study of HCW9218 for the treatment of advanced/metastatic solid tumor cancer (except pancreatic and primary brain cancers). HCW9218 is a novel bi-functional fusion protein complex administered by subcutaneous (SC) injection. It is comprised of a soluble fusion of two human TGFβRII domains, human tissue factor, and human IL-15, and a second soluble fusion of two human TGFβRII domains and a sushi domain of human IL-15Rα. HCW9218 activates IL-15R signaling on effector immune cells and the dimeric TGFβRII functions as a "trap" for all three human TGF-β isoforms.


Eligibility criteria: Inclusion Criteria:

* Histologically or cytologically confirmed advanced/metastatic solid tumor cancer (except pancreatic and primary brain cancers), has failed at least 2 prior lines of therapy given either in the recurrent or metastatic setting and must be refractory to or intolerant of existing therapy(ies) known to provide clinical benefit for their condition.
* Measurable disease per RECIST v 1.1.
* Acute effects of any prior therapy must have resolved to baseline or Grade ≤1 NCI CTCAE v5 except for AEs not constituting a safety risk by enrolling Investigator judgment.
* Age 18 years or older at the time of consent.
* ECOG Performance Status 0 or 1.
* Evidence of adequate organ function within 14 days prior to enrollment as defined in Section 4.1.6.
* Adequate pulmonary function with PFTs \>50% FEV1 if symptomatic or known impairment.
* Sexually active persons of child-bearing potential or with partners of childbearing potential must agree to use a highly effective form of contraception (refer to Section 4.1.10 for acceptable methods) for at least 28 days after the last dose of HCW9218.
* Provides voluntary written consent prior to the performance of any research related activity.

Exclusion Criteria:

* Pregnant or breastfeeding.
* History of clinically significant vascular disease, including any of the following within 6 months prior to start of study treatment: MI or unstable angina, percutaneous coronary intervention, bypass grafting, ventricular arrhythmia requiring medication, stroke or transient ischemic attack, symptomatic peripheral arterial disease.
* Marked baseline prolongation of QT/QTc interval (e.g., demonstration of a QTc interval greater or equal to 470 milliseconds by Fridericia's correction).
* Known or suspected untreated CNS metastases.
* Anti-cancer treatment including surgery, radiotherapy, chemotherapy, other immunotherapy, or investigational therapy within 14 days before treatment start.
* Other prior malignancy except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the subject is currently in complete remission, or any other cancer from which the subject has been disease-free for 3 years after surgical treatment.
* Known hypersensitivity or history of allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study.
* Prior therapy with TGF-β antagonist, IL-15 or analogs.
* Concurrent use of St. John's wort and and/or other herbal CYP modulators within 7 days of Day 1. Must agree to not use during study treatment through the end of treatment visit to be eligible.
* Known autoimmune disease requiring active treatment. Persons with a condition requiring systemic treatment with either corticosteroids (\> 10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of enrollment. Inhaled or topical steroids, and adrenal replacement steroid doses ≤ 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
* Active systemic infection requiring parenteral antibiotic therapy. All prior infections must have resolved following optimal therapy.
* Prior organ allograft or allogeneic transplantation.
* Known HIV-positive or AIDS.
* Psychiatric illness/social situations that would limit compliance with study requirements.
* Other illness or a medical issue that in the opinion of the Investigator would exclude the subject from participating in this study

Primary outcomes:
measure: The primary objective of the dose finding component is to determine the maximum tolerated dose (MTD) of HCW9218
timeFrame: through study completion, an average of 12 months
Secondary outcomes:
measure: Estimate response rate (complete response (CR), partial response (PR) or stable disease (SD)
timeFrame: 3 months after 1st dose
measure: Estimate response rate (complete response (CR), partial response (PR) or stable disease (SD)
timeFrame: 6 months after 1st dose
measure: Estimate response rate (complete response (CR), partial response (PR) or stable disease (SD)
timeFrame: 12 months after 1st dose
measure: Estimate progression of overall survival (OS)
timeFrame: 6 months after 1st dose
measure: Estimate progression free survival (PFS)
timeFrame: 6 months after 1st dose
measure: Estimate progression free survival (PFS)
timeFrame: 1 year after 1st dose
measure: Estimate progression of overall survival (OS)
timeFrame: 1 year after 1st dose
Other outcomes:
Locations:
city: Minneapolis
country: United States
facility: Masonic Cancer Center - University of Minnesota
state: Minnesota
Study officials:
affiliation: Masonic Cancer Center, Univeristy of Minnesota
name: Melissa Geller, MD
role: PRINCIPAL_INVESTIGATOR
References: