XTX301 in Patients With Advanced Solid Tumors

This is a first-in-human, multicenter, Phase 1, open-label study designed to evaluate the

safety, tolerability, PK, PD, immunogenicity, and efficacy of XTX301, a tumor-activated

interleukin-12, as monotherapy in patients with advanced solid tumors.

Part 1A will examine XTX301 monotherapy in a standard 3+3 dose escalation design. Based on

the results of Part 1A, patients with select advanced solid tumors will be enrolled in Part

1B, which will evaluate XTX301 monotherapy in relation to specific PD biomarkers.

Inclusion Criteria

• Disease Criteria: Part 1A - Any histologically or cytologically confirmed solid tumor malignancy that is locally advanced or metastatic and has failed standard therapy, standard therapy does not confer survival benefit, or standard therapy is not available. Part 1B- Any histologically or cytologically confirmed solid tumor malignancy among the tumor types outlined below, that is locally advanced or metastatic and has failed standard therapy, standard therapy does not confer survival benefit, or standard therapy is not available. Patients with the following tumor types are eligible for Part 1B: melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma, triple-negative breast cancer (TNBC), MSI-H/dMMR colorectal cancer, MSI-H/dMMR endometrial cancer, prostate cancer, ovarian cancer, pancreatic cancer, and microsatellite stable colorectal cancer. - ECOG performance status of 0-2 - Adequate organ function - Tumor tissue samples: Part 1A: archival tumor tissue available or provide a fresh tumor biopsy. Part 1B: patients must have lesions amenable to biopsy and be willing and able to provide fresh tumor biopsies before and after initiation of treatment - Patients with recent major surgery must have adequately recovered with no ongoing complications from the surgery before receiving study drug Exclusion Criteria: - Prior treatment with IL-12 therapy (any form, e.g. recombinant human, prodrug, intratumoral, etc.) - Known liver metastasis based on imaging - Possible area of ongoing necrosis (non-disease-related), such as active ulcer, nonhealing wound, or intercurrent bone fracture - Active primary central nervous system (CNS) malignancy, CNS metastases, and/or carcinomatous meningitis - Active autoimmune disease - History of Grade ≥ 3 immune-related adverse events associated with prior immunotherapy unless these were adequately resolved with therapy within 14 days - A diagnosis of immunodeficiency; receiving chronic systemic therapy exceeding prednisone 10 mg daily or equivalent or any other form of immunosuppressive therapy within 7 days before the first dose of study drug - Active hepatitis B or active hepatitis C infection - Prior treatment with gene therapy, organ transplant, or hematopoietic stem-cell transplant