HCW9218 in Select Advanced Solid Tumors

• ClinicalTrials.gov Identifier: NCT05322408
• Recruitment Status: Recruiting
• First Posted: April 11, 2022
• Last Update Posted: April 20, 2022
• Sponsor: Masonic Cancer Center, University of Minnesota
• Information provided by (Responsible Party): Masonic Cancer Center, University of Minnesota

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Solid Tumor	Drug: HCW9218	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Actual Study Start Date: April 1, 2022
• Estimated Primary Completion Date: January 2027
• Estimated Study Completion Date: January 2027

Arms and Interventions

Arm	Intervention/treatment
Experimental: Administer HCW9218; Administer HCW9218 as monotherapy at assigned dose by SC injection once every 3 weeks. Dose Level -1 - 0.1 mg/kg; - (start) 0.25 mg/kg; - 0.5 mg/kg; - 0.8 mg/kg; - 1.2 mg/kg	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.; Other Name: Monotherapy

Outcome Measures

Primary Outcome Measures :

1. The primary objective of the dose finding component is to determine the maximum tolerated dose (MTD) of HCW9218 [ Time Frame: through study completion, an average of 12 months ]
   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.

Secondary Outcome Measures :

1. Estimate response rate (complete response (CR), partial response (PR) or stable disease (SD) [ Time Frame: 3 months after 1st dose ]
   Response rate will be estimated by a simple proportion with 95% confidence limits if sufficient numbers exist
2. Estimate response rate (complete response (CR), partial response (PR) or stable disease (SD) [ Time Frame: 6 months after 1st dose ]
   Response rate will be estimated by a simple proportion with 95% confidence limits if sufficient numbers exist
3. Estimate response rate (complete response (CR), partial response (PR) or stable disease (SD) [ Time Frame: 12 months after 1st dose ]
   Response rate will be estimated by a simple proportion with 95% confidence limits if sufficient numbers exist
4. Estimate progression of overall survival (OS) [ Time Frame: 6 months after 1st dose ]
   Estimated with Kaplan-Meier curves
5. Estimate progression free survival (PFS) [ Time Frame: 6 months after 1st dose ]
   Estimated with Kaplan-Meier curves
6. Estimate progression free survival (PFS) [ Time Frame: 1 year after 1st dose ]
   Estimated with Kaplan-Meier curves
7. Estimate progression of overall survival (OS) [ Time Frame: 1 year after 1st dose ]
   Estimated with Kaplan-Meier curves

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Contacts and Locations

Contacts

Contact: Cancer Center Info Nurse; 612-624-2620; ccinfo@umn.edu

Locations

United States, Minnesota

Masonic Cancer Center - University of Minnesota; Recruiting

Minneapolis, Minnesota, United States, 55455

Contact: Melissa Geller, MD 612-626-3111 gelle005@umn.edu

Sponsors and Collaborators

Masonic Cancer Center, University of Minnesota

Investigators

• Principal Investigator: Melissa Geller, MD; Masonic Cancer Center, Univeristy of Minnesota

More Information

• Responsible Party: Masonic Cancer Center, University of Minnesota
• ClinicalTrials.gov Identifier: NCT05322408
• Other Study ID Numbers: 2021LS143
• First Posted: April 11, 2022
• Last Update Posted: April 20, 2022
• Last Verified: April 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Neoplasms