XTX301 in Patients With Advanced Solid Tumors

NCT05684965 | Recruiting Phase 1 FDA Drug

• 1 other identifier: XTX301-01/02-001
• Study Type: interventional
• Target: 358
• Locations: 1 country
• Sites: 11

Brief Summary

This is a first-in-human, multicenter, Phase 1/2, open-label study designed to evaluate the safety and tolerability of XTX301 as monotherapy in patients with advanced solid tumors.

Conditions

Advanced Solid Tumor

Outcome Measures

Primary Outcomes (3)

• Incidence of Dose Limiting Toxicities (DLTs) (Part 1A only)

  From the first dose of the study drug at Cycle 1 Day 1 up to next applicable cycle visit (Cycle 2 Day 1 or Cycle 3 Day 1). Approximately 21 to 42 days. Each cycle is 21 days.

• Incidence of treatment-emergent adverse events (TEAEs) and changes in clinical laboratory values

  Up to 24 months

• Investigator-assessed objective response rate (ORR) per RECIST 1.1 (Phase 2 only)

  up to 24 months

Secondary Outcomes (14)

• Plasma concentrations of XTX301

  Up to 24 months

• Maximum observed plasma concentration (Cmax)

  Up to 24 months

• Time of maximum observed concentration (Tmax)

  Up to 24 months

• Trough concentration (Ctrough)

  Up to 24 months

• Area under the curve (AUC)

  Up to 24 months

Study Arms (2)

Phase 1 - XTX301 Monotherapy Dose Escalation and Pharmacodynamics Expansion

EXPERIMENTAL

Part 1A Dose Escalation of XTX301 administered in ascending doses to patients with advanced solid tumors to assess the safety and tolerability and determine/define MTD and/or the highest recommended Phase 2 dose (RP2D). Part 1B Evaluation of XTX301 in patients with selected advanced solid tumors to further characterize the pharmacodynamics profile of XTX301.

Drug: XTX301

Phase 2 - XTX301 Monotherapy Dose Expansion in Disease-Specific Cohorts

EXPERIMENTAL

Phase 2 will further evaluate the safety and antitumor activity/efficacy of XTX301 monotherapy in disease-specific expansion cohorts of patients with select tumors, namely: * Cohort 2A: head and neck squamous cell carcinoma (HNSCC) * Cohort 2B: melanoma (patients with uveal melanoma are excluded) * Cohort 2C: non-small cell lung cancer (NSCLC) * Cohort 2D: ovarian cancer * Cohort 2E: castrate-resistant prostate cancer (CRPC) * Cohort 2F: triple-negative breast cancer (TNBC)

Drug: XTX301

Interventions

XTX301 DRUG

XTX301 monotherapy

Phase 1 - XTX301 Monotherapy Dose Escalation and Pharmacodynamics Expansion; Phase 2 - XTX301 Monotherapy Dose Expansion in Disease-Specific Cohorts

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Xilio Development, Inc.: lead

Study Sites (11)

University of California, Davis Comprehensive Cancer Center

Sacramento, California, 95817, United States

RECRUITING

Yale Cancer Center

New Haven, Connecticut, 06510, United States

RECRUITING

HealthPartners Frauenshuh Cancer center

Saint Louis Park, Minnesota, 55426, United States

RECRUITING

Washington University School of Medicine

St Louis, Missouri, 63110, United States

RECRUITING

Hackensack University Medical Center

Hackensack, New Jersey, 07601, United States

RECRUITING

The Gabrail Pharmacology Phase 1 Research Center

Canton, Ohio, 44718, United States

RECRUITING

University Hospital Cleveland Medical Center

Cleveland, Ohio, 44106, United States

RECRUITING

The Ohio State University Wexner Medical Center

Columbus, Ohio, 43221, United States

RECRUITING

University of Pittsburgh Medical Center-Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

RECRUITING

Tranquil Clinical Research

Webster, Texas, 77598, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

RECRUITING

Central Study Contacts

Xilio Medical Affairs

CONTACT

(857) 524-2466; medicalaffairs@xiliotx.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 21, 2022
• First Posted: January 13, 2023
• Study Start: May 11, 2023
• Primary Completion (Estimated): February 1, 2027
• Study Completion (Estimated): February 1, 2027
• Last Updated: September 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

US (11)