XTX301 in Patients with Advanced Solid Tumors
- Registration Number
- NCT05684965
- Lead Sponsor
- Xilio Development, Inc.
- 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.
- Detailed Description
This is a first-in-human, multicenter, Phase 1/2, open-label study designed to evaluate the safety, tolerability, PK, PD, immunogenicity, and antitumor activity/efficacy of XTX301, a tumor-activated interleukin-12, as monotherapy in patients with advanced solid tumors.
Phase 1. 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.
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: head and neck squamous cell carcinoma (HNSCC), melanoma, non-small cell lung cancer (NSCLC), ovarian cancer, castrate-resistant prostate cancer (CRPC), triple-negative breast cancer (TNBC)
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 358
• 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.
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 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
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description Phase 1 - XTX301 Monotherapy Dose Escalation and Pharmacodynamics Expansion XTX301 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. Phase 2 - XTX301 Monotherapy Dose Expansion in Disease-Specific Cohorts XTX301 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 * 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)
- Primary Outcome Measures
Name Time Method Incidence of Dose Limiting Toxicities (DLTs) (Part 1A only) Cycle 1 Day 1 up to just prior to the second dose of the study drug at Cycle 2 Day 1 (approximately 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 Outcome Measures
Name Time Method 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 Half-life (T1/2) Up to 24 months Systemic clearance (CL) Up to 24 months Volume of distribution (Vd) Up to 24 months Antidrug antibody (ADA) occurrence and titer in serum Up to 24 months Investigator-assessed objective response rate (ORR) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 (Phase 1 only) Up to 24 months Duration of response (DOR) (Phase 2 only) up to 24 months Disease control rate (Phase 2 only) up to 24 months Progression-free survival (PFS) (Phase 2 only) up to 24 months Overall survival (OS) (Phase 2 only) up to 24 months
Trial Locations
- Locations (11)
University of California, Davis Comprehensive Cancer Center
🇺🇸Sacramento, California, United States
Yale Cancer Center
🇺🇸New Haven, Connecticut, United States
HealthPartners Frauenshuh Cancer center
🇺🇸St. Louis Park, Minnesota, United States
Washington University School of Medicine
🇺🇸Saint Louis, Missouri, United States
Hackensack University Medical Center
🇺🇸Hackensack, New Jersey, United States
The Gabrail Pharmacology Phase 1 Research Center
🇺🇸Canton, Ohio, United States
University Hospital Cleveland Medical Center
🇺🇸Cleveland, Ohio, United States
The Ohio State University Wexner Medical Center
🇺🇸Columbus, Ohio, United States
University of Pittsburgh Medical Center-Hillman Cancer Center
🇺🇸Pittsburgh, Pennsylvania, United States
Tranquil Clinical Research
🇺🇸Webster, Texas, United States
Medical College of Wisconsin
🇺🇸Milwaukee, Wisconsin, United States