XTX301 in Patients With Advanced Solid Tumors

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Advanced Solid Tumor

Intervention / Treatment
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* Drug: XTX301


Participation Criteria
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Eligibility Criteria
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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, 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 1A: archival tumor tissue available or provide a fresh tumor biopsy. 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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Part 1A - XTX301 Monotherapy Dose Escalation<br>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). | Drug: XTX301<br>* XTX301 monotherapy<br>|
| Experimental: Part 1B - XTX301 Monotherapy in Select Tumor Types<br>Part 1B XTX301 will contribute to the assessment of safety and feasibility of XTX301 and will additionally allow pharmacodynamic assessment of XTX301. | Drug: XTX301<br>* XTX301 monotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 (Part 1A & 1B) |  | Up to 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 |  | Up to 24 months |