HCW9218 in Select Advanced Solid Tumors

Solid Tumor Clinical Trial

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT05322408
• Other study ID #: 2021LS143
• Status: Active, not recruiting
• Phase: Phase 1
• Start date: April 1, 2022
• Est. completion date: February 2026

Study information

• Verified date: February 2024
• Source: Masonic Cancer Center, University of Minnesota
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 18
• Est. completion date: February 2026
• Est. primary completion date: February 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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-ß 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

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumor

Intervention

Drug:
• HCW9218
HCW9218 at the assigned dose level is administered as a subcutaneous injection once every 3 weeks for a minimum of 2 treatment cycles unless medically contraindicated.

Locations

Country	Name	City	State
United States	Masonic Cancer Center - University of Minnesota	Minneapolis	Minnesota

Sponsors (1)

Lead Sponsor	Collaborator
Masonic Cancer Center, University of Minnesota

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	The primary objective of the dose finding component is to determine the maximum tolerated dose (MTD) of HCW9218	Given that little to no toxicity is expected, the MTD will be determined using an adaptation of the continual reassessment method (CRM) (O'Quigley, 1996) starting with 1 patient cohorts.	through study completion, an average of 12 months
Secondary	Estimate response rate (complete response (CR), partial response (PR) or stable disease (SD)	Response rate will be estimated by a simple proportion with 95% confidence limits if sufficient numbers exist	3 months after 1st dose
Secondary	Estimate response rate (complete response (CR), partial response (PR) or stable disease (SD)	Response rate will be estimated by a simple proportion with 95% confidence limits if sufficient numbers exist	6 months after 1st dose
Secondary	Estimate response rate (complete response (CR), partial response (PR) or stable disease (SD)	Response rate will be estimated by a simple proportion with 95% confidence limits if sufficient numbers exist	12 months after 1st dose
Secondary	Estimate progression of overall survival (OS)	Estimated with Kaplan-Meier curves	6 months after 1st dose
Secondary	Estimate progression free survival (PFS)	Estimated with Kaplan-Meier curves	6 months after 1st dose
Secondary	Estimate progression free survival (PFS)	Estimated with Kaplan-Meier curves	1 year after 1st dose
Secondary	Estimate progression of overall survival (OS)	Estimated with Kaplan-Meier curves	1 year after 1st dose