RTX-321 Monotherapy in Patients With HPV 16+ Tumors

Study Overview
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Brief Summary
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This is an open-label, multicenter, multiple-ascending dose, FIH, Phase 1 study of RTX-321 for the treatment of patients that are HLA-A*02:01 positive with persistent, recurrent, or metastatic, unresectable, HPV 16+ cancers.

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-321 in adult patients with persistent, recurrent, or metastatic, unresectable cervical cancer (squamous, adeno, or adenosquamous histology), HNSCC, or squamous cell cancer of the anal canal that is not amenable to curative therapy. Prior to study screening, all patients must be confirmed to be HLA-A*02:01 positive. Documentation of an HPV 16+ tumor is required at prescreening for patients with cervical cancer and HNSCC. RTX-321 is a cellular therapy that expresses 4-1BBL, IL-12, and HPV-16 Antigen with the goal of harnessing the innate and adaptive immune systems for the treatment of cancer. The study will include a monotherapy dose escalation phase followed by an expansion phase.

Official Title
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A Phase 1 Study of RTX-321 for the Treatment of Patients With Advanced Malignancies Associated With Human Papillomavirus-16 Infection

Conditions
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Cervical Cancer, Head and Neck Cancer, Anal Cancer

Intervention / Treatment
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* Drug: RTX-321


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 0 or 1 Histologically confirmed diagnosis by the local laboratory of persistent, recurrent, or metastatic, unresectable cervical cancer (squamous, adeno, or adenosquamous histology), HNSCC, or squamous cell cancer of the anal canal that is not amenable to curative therapy. All patients must have experienced disease progression following platinum-based or mitomycin C-based chemotherapy administered in the persistent, recurrent, or metastatic setting. All patients with programmed death-ligand 1 (PD-L1) positive cervical cancer and those with HNSCC must have received or have been determined to be ineligible for immunotherapy with a PD-1 or PD-L1 inhibitor. All patients with cervical cancer will have received or have been determined to be ineligible for bevacizumab. Confirmation of HLA-A*02:01 positive status by central testing. In patients with cervical cancer or HNSCC, confirmation of HPV 16 within the tumor either from historical pathology result (using an FDA-approved HPV testing method, patients with cervical cancer only) or based on central laboratory analysis of a tumor sample. Patients with anal cancer will not be required to have prospective determination of HPV 16 positive status prior to enrollment. 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, without myeloid growth factor support for ≥1 week Platelet count ≥100 × 103/μL, without platelet transfusion for ≥1 week Hemoglobin ≥9 g/dL, without red blood cell transfusion for ≥2 weeks 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-321 Dose Escalation<br>Phase 1: RTX-321 administered intravenously on Day 1 of each cycle monotherapy dose escalation | Drug: RTX-321<br>* RTX-321 monotherapy<br>|
| Experimental: RTX-321 Dose Expansion<br>Phase 1: RTX-321 administered intravenously on Day 1 of each cycle. | Drug: RTX-321<br>* RTX-321 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: | Measured by incidence of Treatment Emergent Adverse Events (TEAEs) | up to 30 months | 
| Dose limiting toxicities (DLTs) of RTX-321: | As determined by incidence and severity of adverse events (AEs) | up to 30 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacodynamics (PD) of RTX-321: | As measured by the changes in number of CD8+ T-cells in peripheral blood using flow cytometry | up to 30 months | 
| Pharmacokinetics (PK) of RTX-321: | As measured by the detection of the number of RTX-321 cells using flow cytometry | up to 30 months | 
| Anti-tumor activity of RTX-321 | measured by duration of response (DoR) | up to 30 months | 
| Anti-tumor activity of RTX-321 | Measured by overall survival (OS) | up to 30 months | 
| Anti-tumor activity of RTX-321 | Measured by progression free survival (PFS) | up to 30 months | 
| Anti-tumor activity of RTX-321 | Measured by overall response rate (ORR) | up to 30 months |