Overview
This is a first-in-human, multicenter, Phase 1, open-label study designed to evaluate the safety and tolerability of XTX301 as monotherapy in patients with advanced solid tumors.
Description
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.
Eligibility
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,T-cell lymphoma, 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 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