A Phase 1 Study of the Safety and Tolerability of CTX-10726

Inclusion Criteria40

• Age 18 years or older.
• Patients must have a histologically or cytologically confirmed diagnosis of locally advanced unresectable or metastatic disease that is relapsed/refractory to standard therapy or for which no effective standard therapy is available, including:
• a: Renal Cell Carcinoma (RCC)
• Histologically confirmed diagnosis of renal cell carcinoma (with clear cell component) with advanced or metastatic disease that is not amenable to cure by surgery or other means.
• Patients who have progressed after a minimum of 2 doses of a programmed cell death 1 (PD-1)/ programmed cell death ligand 1 (PDL1) treatment.
• Patients must have received at least one regimen including a tyrosine kinase inhibitor (TKI).
• Patients who received immunomodulatory drugs (thymosin, interferon, interleukin, etc.) within 2 weeks before the first dose or received major surgical treatment within 3 weeks before the first dose are not eligible.
• b: Hepatocellular Carcinoma (HCC)
• Patients who have progressed after a minimum of 2 doses of a PD-1/PDL1 treatment.
• Patient must have received one of the following regimens: ipilimumab+nivolumab, tremelimumab+durvalumab, atezolizumab+bevacizumab or lenvatinib+pembrolizumab.
• Hepatic function: Child -Pugh A and Child-Pugh B7.
• Receipt of local area treatment of the liver more than 4 weeks prior to the first dose is allowed.
• c. Gastroesophageal Cancer (GC)
• Patients who have progressed after a minimum of 2 doses of a PD-1/PDL1 treatment.
• Patients must have received prior treatment with platinum-based chemotherapy.
• d: Endometrial Cancer (EC)
• Patients must have received at least 1 cycle of platinum-based chemotherapy.
• Patients with newly diagnosed advanced endometrial cancer that have persistent lesion(s) after standard treatment with surgery and chemotherapy ± radiotherapy.
• Patients with MSI- high or deficient DNA mismatch repair (dMMR) tumors who have progressed after a minimum of 2 doses of a PD-1/PDL1 treatment.
• \. Patients must have measurable disease per RECIST 1.1. Tumor sites that are considered measurable must not have received prior radiation.
• \. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• \. Adequate organ function including:
• Bone marrow function defined by absolute neutrophil (ANC) of ≥ 1.5×109/L, platelet count of ≥ 100.0×109/L, and hemoglobin of ≥ 9.0 g/dL (with or without transfusion).
• Hepatic function defined as serum total bilirubin ≤ 1.5 × ULN (<3 x ULN in patients with Gilbert's syndrome), AST/ALT ≤ 2.5 × ULN (or ≤ 5 × ULN in patients with liver metastases).
• Renal function defined as creatinine clearance ≥ 30 mL/min by Cockcroft Gault equation.
• Cardiac function with Left Ventricular Ejection Fraction (LVEF) ≥ 50%.
• \. Female patients must be surgically sterile (or have a monogamous partner who is surgically sterile) or be at least 2 years postmenopausal or commits to use 2 acceptable forms of birth control (defined as the use of an intrauterine device, a barrier method with spermicide, condoms, any form of hormonal contraceptives) or abstinence for the duration of the study and for 4 months following the last dose of study treatment. Male patients must be sterile (biologically or surgically) or commit to the use of a reliable method of birth control (condoms with spermicide) for the duration of the study and for 4 months following the last dose of study treatment.
• \. Female patients who are women of childbearing potential (WOCBP) must have a negative serum pregnancy test at Screening within 7 days of dosing with CTX-10726.
• \. Prior anticancer therapy > 28 days (or 2 half-lives for proteins, whichever is shorter), radiotherapy > 7 days (concurrent localized palliative radiotherapy is allowed during CTX-10726 treatment with medical monitor approval), therapeutic surgical intervention > 21 days, blood transfusion > 14 days, or biopsy or minor surgery (excluding placement of vascular access devices) > 7 days prior to the first dose of CTX-10726.
• \. Resolution of all prior anti-cancer therapy toxicities ≤ Grade 2 (excluding alopecia).
• \. Capable of understanding and complying with protocol requirements
• \. Signed and dated institutional review board (IRB) approved informed consent form (ICF) before any protocol-directed screening procedures are performed.
• Active HCV-infected subjects (HCV antibody positive and HCV-RNA levels above the lower limit of detection).
• Patients that received attenuated vaccination within 4 weeks prior to screening or planning to receive attenuated vaccination during the study period.
• Current or recent systemic therapy with immunosuppressive agents within 7 days before the start of CTX-10726 treatment. Topical, intranasal, intraocular, or inhaled corticosteroids and physiologic replacement (≤ 10 mg/day prednisone or equivalent) for patients with adrenal insufficiency are allowed.
• Active autoimmune disease or medical conditions requiring chronic steroid (i.e., > 10 mg/day prednisone or equivalent) or immunosuppressive therapy. Patients with a prior history of autoimmune disease may be eligible following discussion with the Medical Monitor.
• Active or prior documented idiopathic pulmonary fibrosis or idiopathic pneumonia; current acute lung disease, interstitial lung disease or pneumonia (except localized interstitial pneumonia due to radiotherapy induction), pulmonary fibrosis, severe respiratory distress, pulmonary insufficiency or continuous oxygenation.
• Other medical conditions in the opinion of the Investigator and/or Sponsor Medical Monitor may interfere with the conduct and/or interpretation of the current study, including:
• Congestive heart failure (> New York Heart Association Class II), active coronary artery disease, unevaluated new onset angina within 3 months or unstable angina (angina symptoms at rest) or clinically significant cardiac arrhythmias.
• QTc interval (using Fridericia correction calculation) > 480 msec.