RTX-321 Monotherapy in Patients With HPV 16+ Tumors

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

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.

Study Overview

• Status: Terminated
• Conditions: Cervical Cancer; Head and Neck Cancer; Anal Cancer
• Intervention / Treatment: Drug: RTX-321

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 9
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35249
      • University of Alabama
  • California
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic & Research Institute
  • Colorado
    • Aurora, Colorado, United States, 80045
      • University of Colorado Cancer Center
  • Missouri
    • Saint Louis, Missouri, United States, 63110
      • Washington University
  • New York
    • New York, New York, United States, 10016
      • Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73104
      • OU Health Stephenson Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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).

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RTX-321 Dose Escalation; Phase 1: RTX-321 administered intravenously on Day 1 of each cycle monotherapy dose escalation	Drug: RTX-321; RTX-321 monotherapy
Experimental: RTX-321 Dose Expansion; Phase 1: RTX-321 administered intravenously on Day 1 of each cycle.	Drug: RTX-321; RTX-321 monotherapy

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Rubius Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): April 8, 2021
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: December 8, 2020
• First Submitted That Met QC Criteria: December 16, 2020
• First Posted (Actual): December 17, 2020

Study Record Updates

• Last Update Posted (Estimate): December 8, 2022
• Last Update Submitted That Met QC Criteria: December 6, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Rectal Neoplasms; Anus Diseases; Anus Neoplasms
• Other Study ID Numbers: RTX-321-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No