hcw9218 in select advanced solid tumors

Conditions: Solid Tumor

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