RTX-224 Monotherapy in Patients With Solid Tumors

Study Overview
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Brief Summary
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This is an open-label, multidose, first-in-human (FIH), Phase 1/2 study of RTX-224 for the treatment of patients with relapsed or refractory (R/R), or locally advanced solid tumors.

Detailed Description
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This is a Phase 1, open label, multicenter, multidose, first-in-human (FIH), dose escalation and expansion to determine the safety and tolerability, recommended phase 2 dose, and pharmacology, and antitumor activity of RTX-224 in adult patients with persistent, recurrent, or metastatic, unresectable solid tumors. The study will include a monotherapy dose escalation phase followed by an expansion phase.

Official Title
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A Phase 1/2 Study of RTX-224 for the Treatment of Patients With Advanced Solid Tumors

Conditions
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Non Small Cell Lung Cancer, Cutaneous Melanoma, Head and Neck Squamous Cell Carcinoma, Urothelial Carcinoma, TNBC - Triple-Negative Breast Cancer

Intervention / Treatment
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* Drug: RTX-224


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed written informed consent obtained prior to study procedures Patients ≥18 years with an ECOG of 0 or 1 R/R, or locally advanced, unresectable, and histologically or cytologically confirmed (a) NSCLC, (b) cutaneous melanoma, (c) HNSCC, (d) UC, or (e) TNBC, which are refractory to or otherwise ineligible for treatment with standard-of-care treatments Prior therapy in each disease setting must include the following: NSCLC: Patients must have experienced disease progression following platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. Patients with EGFR, ALK, ROS-1, or other actionable mutations should have previously received or been ineligible for therapies targeting their respective mutation(s). Cutaneous melanoma: Patients must have experienced disease progression following a PD-1 or PD-L1 inhibitor. Patients with V600E mutations should have previously received or been ineligible for approved BRAF inhibitor or MEK inhibitor therapy. HNSCC: Patients must have experienced disease progression following platinum-based combination chemotherapy and a PD-1 or PD-L1 inhibitor. UC: Patients must have experienced disease progression following platinum-based combination chemotherapy and a PD-1 or PD-L1 inhibitor. TNBC: Patients must have experienced disease progression following single-agent or combination chemotherapy. Patients with BRCA1/2 mutations should have previously received or been ineligible for an approved PARP inhibitor; patients who are PD-L1 positive should have received or been ineligible for an approved PD-1 or PD-L1 inhibitor. Disease must be measurable per Response Evaluation Criteria The shorter of 28 days or 5 half-lives must have elapsed since the completion of prior therapy, before initiation of study treatment. Adequate Organ Function as Defined by the protocol: AST and ALT ≤3 × the upper limit of normal (ULN) Except in documented cases of Gilbert syndrome, total bilirubin ≤1.5 × ULN Serum albumin ≥2.5 g/dL Serum or plasma creatinine ≤1.5 × ULN and/or glomerular filtration rate ≥50 mL/min/1.73 calculated by the Cockcroft-Gault formula Absolute neutrophil count ≥1 × 103/μL Platelet count ≥100 × 103/μL Hemoglobin ≥9 g/dL Exclusion Criteria: Patient has central nervous system (CNS) involvement. If the patient fulfills the following 3 criteria, she/he is eligible for the trial after consultation with the Sponsor Medical Monitor. Completed prior therapy for CNS metastases (radiation and/or surgery) CNS tumor(s) is clinically stable at the time of enrollment Patient does not require corticosteroid or antiepileptic therapy for management of CNS metastases Known hypersensitivity to any component of study treatment or excipients. Positive antibody screen using institution's standard type and screen test. Clinically significant, active and uncontrolled infection, including human immunodeficiency virus (HIV), Hepatitis B virus (HBV), or Hepatitis C virus (HCV).

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: RTX-224 Dose Escalation<br>Phase 1: RTX-224 monotherapy dose escalation in Solid Tumors, administered intravenously on Day 1 of each cycle. | Drug: RTX-224<br>* RTX-224 monotherapy<br>|
| Experimental: RTX-224 Dose Expansion<br>Phase 2: RTX-224 monotherapy dose expansion in Solid Tumors, administered intravenously on Day 1 of each cycle. | Drug: RTX-224<br>* RTX-224 monotherapy<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Assessment by rate of Adverse Events (AEs) | Measured by incidence of Treatment Emergent Adverse Events (TEAEs) | up to 30 months | 
| Dose limiting toxicities (DLTs) of RTX-224 | As determined by incidence and severity of adverse events | up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics (PD) of RTX-224 | As measured by the changes in immune cell populations, e.g., T cells and NK cells | up to 30 months | 
| Pharmacokinetics (PK) of RTX-224 | Maximum concentration (Cmax) of RTX-224 cells (positive for both 4-1BBL and IL-12 using flow cytometry) in blood after administration will be measured. | up to 30 months | 
| Pharmacokinetics (PK) of RTX-224 | Time to maximum concentration (tmax) of RTX-224 cells (positive for both 4-1BBL and IL-12 using flow cytometry) in blood after administration will be measured. | up to 30 months | 
| Anti-tumor activity of RTX-224 | As measured by duration of response (DoR) | up to 30 months | 
| Anti-tumor activity of RTX-224 | As measured by overall survival (OS) | up to 30 months | 
| Anti-tumor activity of RTX-224 | As measured by progression free survival (PFS) | up to 30 months | 
| Anti-tumor activity of RTX-224 | As measured by disease control rate (DCR) | up to 30 months | 
| Anti-tumor activity of RTX-224 | As measured by objective response rate (ORR) | up to 30 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Solid Tumor, Advanced Solid Tumors