A Phase 1, Open-Label, Multiple-Ascending Dose Study of the Safety and Tolerability of CTX-10726 in Patients With Advanced Malignancies
This is a Phase 1, open-label, first-in-human study of CTX-10726 monotherapy in patients with metastatic or locally advanced malignancies. The study will be conducted in 2 Cohorts: Cohort 1 Dose Escalation and Cohort 2 Dose Expansion.
⁃ 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:
‣ 2a: 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.
• 2b: 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.
• 2c. 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.
• 2d: 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.
• 3\. Patients must have measurable disease per RECIST 1.1. Tumor sites that are considered measurable must not have received prior radiation.
• 4\. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
• 5\. 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%.
• 6\. 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.
• 7\. 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.
• 8\. 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.
• 9\. Resolution of all prior anti-cancer therapy toxicities ≤ Grade 2 (excluding alopecia).
• 10\. Capable of understanding and complying with protocol requirements
• 11\. Signed and dated institutional review board (IRB) approved informed consent form (ICF) before any protocol-directed screening procedures are performed.