IRB Study Number 24-623
Status Recruiting
Institute Taussig Cancer Institute
Description
Primary Objectives
To assess the safety and tolerability of Decoy20
To determine the MTDa and RP2D of Decoy20 during Part 1 and to confirm the safety of the continuous weekly regimen at the RP2Db during Part 2
Secondary Objectives
Immunogenicity evaluation PK evaluation
Preliminary anti-tumor activity
Inclusion Criteria
Must provide written informed consent by signature of an Institutional Review Board (IRB)-approved informed consent form (ICF).
Males or females, age 18 years or older.
Histologically-confirmed diagnosis of locally advanced or metastatic solid tumor. For Part 2, participants must have one of the following locally advanced or metastatic tumor types: HCC, CRC with liver metastasis, urothelial cancer, SCCHN, adenocarcinoma of the pancreas, NSCLC.
Participant must have exhausted all available therapy or have declined treatment or treatment is contraindicated. Participants with tumors that have known actionable molecular alteration such as EGFR, ALK, ROS-1, BRAF, RET, MET, and KRAS must have progressed on directed molecular therapy.
Measurable disease (at least 1 measurable lesion) per RECIST v1.1 as defined by tumor type.
Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Life expectancy of at least 3 months.
Female participants must be of non-childbearing potential (surgically sterile or at least 2 years postmenopausal) or agree to use a highly effective contraception method while receiving treatment with Decoy20 and for 30 days after the last dose of Decoy20. Women of childbearing potential (WCBP) must have a negative serum pregnancy test at Screening and a negative serum or urine test on W1D1 prior to Decoy20 dosing.
Male participants must utilize reliable contraceptive precautions for the duration of Decoy20 treatment and 30 days after the last dose of Decoy20.
Adequate organ function, confirmed by the following laboratory values at Screening: (See protocol)
(See protocol)
Must have recovered from toxicities due to prior therapies, except for Grade 2 alopecia, or Grade 2 NCI CTCAE v5.0 criteria or to the participant's prior baseline.
Willing and able to comply with all scheduled visits, laboratory tests, and other study procedures including mandatory pre-treatment and on-treatment biopsies for participants enrolled in Parts 2a and 2b. Participants for whom a non-significant risk core needle biopsy is medically contradicted may be enrolled with approval by the Sponsor.
Exclusion Criteria
Pregnant or lactating females.
Has an active systemic (viral, bacterial, or fungal) infection or requiring treatment. Infections should be treated, and the participant recovered prior to enrollment in the study.
Received radiotherapy within 28 days of the first dose of Decoy20. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. (Note: Palliative radiation is allowed for non-target lesions provided the radiation field represents less than 50% of bone marrow containing areas subject to approval from the medical monitor).
Received prior chemotherapy, targeted therapy, immunotherapy or any investigational therapy, within 28 days or 5 half-lives from W1D1, whichever is shorter.
Received systemic corticosteroid therapy > 5 mg/day of prednisone or equivalent dose of another corticosteroid within 1 week or 5 half-lives (whichever is shorter) from W1D1 or is expected to require it during the course of the study (topical and inhaled steroids are permitted) or have Medical Monitor approval. Systemic corticosteroids are contraindicated after receiving Decoy20 outside of study specific needs to manage AEs.
Has radiographically detected primary central nervous system (CNS) or CNS metastases or symptomatic CNS involvement (including leptomeningeal carcinomatosis, cranial neuropathies or mass lesions that cause spinal cord compression). Participants with brain metastases (either treated or deemed unnecessary to treat) that have been stable by neuroimaging
for at least 4 weeks will be eligible.
Clinical evidence of significant coagulopathy during Screening (e.g., deep vein thrombosis or pulmonary embolism) or history of significant uncontrolled coagulopathy (participants with HCC must have prothrombin time (PT) < 4 seconds above ULN or international normalized ratio [INR] < 1.7) or participants with diagnosis of a new thrombotic event within 90 days prior to Decoy20 dosing. Superficial vein thrombosis and visceral/splanchnic vein thrombosis primarily associated with the underlying disease, or with controlled coagulation profiles are eligible.
Has an active secondary malignancy in addition to the primary, excluding low-risk neoplasms as determined by the Investigator (e.g., non-metastatic basal cell or squamous cell skin carcinoma and other indolent malignancies will be allowed after discussion with the Sponsor).
Has a history of or active infection with HIV 1 or 2, a history of or active infection with HBV based upon HBV antigenemia or viral load, or positive read for hepatitis C virus ([HCV] viral load >15 IU/mL) at Screening. Hepatitis C RNA testing is not required in participants with negative hepatitis C antibody testing. HBV antibodies are not required in participants with negative HBV surface antigen.
Has a history of known genetic predisposition to HLH/MAS.
Has undergone splenectomy, has an active chronic liver disease, hemochromatosis, primary biliary cirrhosis, primary sclerosing cholangitis, genetic hemochromatosis, history of or planned liver transplant for end-stage liver disease of any etiology, documented history of advanced liver fibrosis or history of cirrhosis and/or hepatic decompensation including ascites requiring paracentesis rather than medical therapy, modified Child-Pugh B or C, clinically relevant hepatic encephalopathy within the preceding 6 months, or variceal bleeding.
Has received a vaccine within 14 days of W1D1.
Has active autoimmune disease (including, but not limited to psoriasis, multiple sclerosis, lupus and rheumatoid arthritis). The use of topical steroids or systemic NSAIDs is acceptable. All other systemic treatment renders the participant non-eligible.
Has a history of significant CNS disease, such as stroke (past history of transient ischemic attacks more than 3 months ago and controlled is allowed) or uncontrolled and unstable epilepsy.
Has severe pulmonary interstitial disease and/or oxygen saturation on room air < 92%.
Baseline QT corrected (QTc) interval of > 470 msec for females and > 450 msec for
New York Heart Association Class III or IV cardiac disease, or myocardial ischemia or infarction within 180 days of Screening, vaso-vagal sensitivity, unstable angina, coronary/peripheral artery bypass graft, worsening/decompensated heart failure within the past 6 months, or any other clinically significant cardiac abnormality (i.e., Grade 4 heart block) that, in the judgement of the Investigator, would pose a health risk to the participant.
Major surgical procedure within 4 weeks prior to first dose of Decoy20, or anticipation of need for a major surgical procedure, during the study. (Note: Placement of a central venous access catheter[s] [e.g., port, or similar] is not considered a major surgical procedure).
Any other acute or chronic medical or psychiatric condition that may increase the risk associated with study participation or Decoy20 administration or that, in the judgment of the Investigator, or Sponsor, would make the participant inappropriate for entry into the study including preexisting conditions which could increase vulnerability to expected toxicities or cytokine-induced inflammation, including abnormal blood chemistries.
Has received investigational therapy within 28 days or 5 half-lives (whichever is shorter) of W1D1.
Unwillingness or inability to comply with procedures required in this protocol.
Known allergy or hypersensitivity to Decoy20 or one of the ingredients of Decoy20.
