XTX301 in Patients With Advanced Solid Tumors

Xilio Development

Status and phase: Enrolling; Phase 1

Conditions: Advanced Solid Tumor

Treatments: Drug: XTX301

Study type: Interventional

Funder types: Industry

Identifiers

NCT05684965

XTX301-01/02-001

Details and patient eligibility

About

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.

Full 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.

Enrollment: 174 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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174 participants in 2 patient groups

Part 1A - XTX301 Monotherapy Dose Escalation

Experimental group

Description:

Part 1A Dose Escalation of XTX301 administered in ascending doses to patients with advanced solid tumors to assess the safety and tolerability and determine the recommended Phase 2 dose (RP2D).

Treatment:

Drug: XTX301

Part 1B - XTX301 Monotherapy in Select Tumor Types

Experimental group

Description:

Part 1B XTX301 will contribute to the assessment of safety and feasibility of XTX301 and will additionally allow pharmacodynamic assessment of XTX301.

Treatment:

Drug: XTX301