Evaluating XTX301 for advanced solid tumors

A First-in-Human, Multicenter, Phase 1/2, Open-Label Study of XTX301 in Patients With Advanced Solid Tumors

This study is testing a new treatment called XTX301 to see if it can safely help people with advanced solid tumors like melanoma, lung cancer, and triple-negative breast cancer.

Quick facts

• Phase: PHASE1; PHASE2
• Study type: Interventional
• Enrollment: 358 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Xilio Development, Inc. (industry)
• Drugs / interventions: chemotherapy, immunotherapy, prednisone
• Locations: 11 sites (Sacramento, California and 10 other locations)
• Trial ID: NCT05684965 on ClinicalTrials.gov

What this trial studies

This is a first-in-human, multicenter, Phase 1/2, open-label study designed to assess the safety and tolerability of XTX301, a tumor-activated interleukin-12, as a standalone treatment for patients with advanced solid tumors. The study will be conducted in two parts: Part 1A will utilize a 3+3 dose escalation design to determine the appropriate dosage, while Part 1B will focus on specific tumor types and evaluate the drug's efficacy in relation to particular biomarkers. Phase 2 will further explore the safety and antitumor activity of XTX301 in disease-specific cohorts, including melanoma, non-small cell lung cancer, and triple-negative breast cancer.

Who should consider this trial

Good fit: Ideal candidates include patients with advanced solid tumors that are locally advanced or metastatic and have failed standard therapy.

Not a fit: Patients with early-stage tumors or those who have not yet undergone standard treatment may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a new therapeutic option for patients with advanced solid tumors that have not responded to standard therapies.

How similar studies have performed: Other studies have shown promise with similar immunotherapy approaches, but this specific treatment is novel.

Eligibility criteria

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, NSCLC, HNSCC, TNBC, cervical cancer, microsatellite instability high/mismatch repair deficient (MSI-H/dMMR) colorectal cancer, or MSI-H/dMMR endometrial cancer. Note: Based on evolving internal and external data, the Sponsor may decide to open a "backfill cohort" in Part 1B for patients with any of the following solid tumors: prostate cancer, ovarian cancer, pancreatic cancer, microsatellite stable colorectal cancer, T-cell lymphoma.

Phase 2 - All patients must have measurable disease at baseline per RECIST 1.1. Additional disease-specific criteria per cohort are as follows:

i. Cohort 2A: head and neck squamous cell carcinoma (HNSCC). Must have histologically or cytologically confirmed locally recurrent or metastatic HNSCC previously treated with 1 to 2 lines of therapy. Unless contraindicated, prior therapy must have included PD-1/PD-L1 inhibitor and/or platinum-based chemotherapy per local and institutional standard of care.

ii. Cohort 2B: melanoma. Must have unresectable or metastatic melanoma previously treated with 1 to 2 lines of therapy in the recurrent or metastatic setting. Unless contraindicated, prior therapy must have included a PD-1/PD-L1 inhibitor alone or in combination. Patients with known BRAF V600-activating mutation must have previously received targeted therapy per local and institutional standard of care. Note: patients with uveal melanoma are excluded.

iii. Cohort 2C: non-small cell lung cancer (NSCLC). Must have histologically confirmed locally advanced or metastatic NSCLC previously treated with 1 to 2 lines of therapy. Unless contraindicated, prior therapy must have included a PD1/PD-L1 inhibitor and a platinum-based regimen, given either concurrently or separately per local and institutional standard of care. Patients with known genomic alteration for which a targeted therapy is approved (e.g. ROS1 fusion, NTRK fusion, BRAF V600E mutation, EGFR mutation, or ALK fusion) must have been previously treated with relevant targeted therapy per local and institutional standard of care.

iv. Cohort 2D: ovarian cancer. Must have histologically confirmed epithelial ovarian cancer, fallopian tube cancer, or primary peritoneal cancer with current platinum-resistant disease per investigator's assessment (e.g. patient is not eligible for further platinum-containing treatment). Patients must have previously experienced a response lasting at least 180 days to first-line platinum-based therapy. Patients who have been unable to tolerate platinum therapy are also eligible. Unless contraindicated, patients with known BRCA mutation must have received a poly(ADP-ribose) polymerase (PARP) inhibitor.

v. Cohort 2E: castrate-resistant prostate cancer (CRPC). Must have metastatic CRPC previously treated with an androgen receptor pathway inhibitor (e.g. abiraterone, enzalutamide, darolutamide, or apalutamide) and/or chemotherapy per local and institutional standard of care. Baseline total testosterone must be ≤ 50 ng/dL (≤ 2.0 nM), and surgical or ongoing medical castration must be maintained throughout the duration of the study.

vi. Cohort 2F: triple-negative breast cancer (TNBC). Must have metastatic TNBC with disease relapse after 2 to 4 previous lines of therapy per local and institutional standard of care. Neoadjuvant and/or adjuvant chemotherapy will count as 1 prior line of therapy. Unless contraindicated, patients with known actionable mutations (e.g. BRCA1 or BRCA2) must have received prior therapy with the corresponding targeted agent per local and institutional standard of care

* ECOG performance status of 0-2 for Phase 1
* ECOG performance status of 0 or 1 for Phase 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

Where this trial is running

Sacramento, California and 10 other locations

• University of California, Davis Comprehensive Cancer Center — Sacramento, California, United States (RECRUITING)
• Yale Cancer Center — New Haven, Connecticut, United States (RECRUITING)
• HealthPartners Frauenshuh Cancer center — Saint Louis Park, Minnesota, United States (RECRUITING)
• Washington University School of Medicine — St Louis, Missouri, United States (RECRUITING)
• Hackensack University Medical Center — Hackensack, New Jersey, United States (RECRUITING)
• The Gabrail Pharmacology Phase 1 Research Center — Canton, Ohio, United States (RECRUITING)
• University Hospital Cleveland Medical Center — Cleveland, Ohio, United States (RECRUITING)
• The Ohio State University Wexner Medical Center — Columbus, Ohio, United States (RECRUITING)
• University of Pittsburgh Medical Center-Hillman Cancer Center — Pittsburgh, Pennsylvania, United States (RECRUITING)
• Tranquil Clinical Research — Webster, Texas, United States (RECRUITING)
• Medical College of Wisconsin — Milwaukee, Wisconsin, United States (RECRUITING)

Study contacts

• Study coordinator: Xilio Medical Affairs

Conditions: Advanced Solid Tumor