RTX-321 Monotherapy in Patients With HPV 16+ Tumors

Phase 1

Terminated

• Conditions: Cervical Cancer; Head and Neck Cancer; Anal Cancer
• Interventions: Drug: RTX-321

• Registration Number: NCT04672980
• Lead Sponsor: Rubius Therapeutics

Brief Summary

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

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 Timeline

• Study First Submitted: 2020-12-08
• Study First Submitted QC: 2020-12-16
• Study First Posted: 2020-12-17
• Study Start: 2021-04-08
• Primary Completion: 2022-11-30
• Study Completion: 2022-11-30
• Status Verified: 2022-12
• Last Update Submitted: 2022-12-06
• Last Update Posted: 2022-12-08

Recruitment & Eligibility

• Status: TERMINATED
• Sex: All
• Target Recruitment: 9

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

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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).

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
RTX-321 Dose Escalation	RTX-321	Phase 1: RTX-321 administered intravenously on Day 1 of each cycle monotherapy dose escalation
RTX-321 Dose Expansion	RTX-321	Phase 1: RTX-321 administered intravenously on Day 1 of each cycle.

Primary Outcome Measures

Name	Time	Method
Safety Assessment by rate of Adverse Events:	up to 30 months	Measured by incidence of Treatment Emergent Adverse Events (TEAEs)
Dose limiting toxicities (DLTs) of RTX-321:	up to 30 months	As determined by incidence and severity of adverse events (AEs)

Secondary Outcome Measures

Name	Time	Method
Pharmacodynamics (PD) of RTX-321:	up to 30 months	As measured by the changes in number of CD8+ T-cells in peripheral blood using flow cytometry
Pharmacokinetics (PK) of RTX-321:	up to 30 months	As measured by the detection of the number of RTX-321 cells using flow cytometry
Anti-tumor activity of RTX-321	up to 30 months	Measured by overall response rate (ORR)

Trial Locations

Locations (10)

The Angeles Clinic & Research Institute; 🇺🇸 Los Angeles, California, United States

OU Health Stephenson Cancer Center; 🇺🇸 Oklahoma City, Oklahoma, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

Virginia Cancer Specialists; 🇺🇸 Fairfax, Virginia, United States

University of Alabama; 🇺🇸 Birmingham, Alabama, United States

Washington University; 🇺🇸 Saint Louis, Missouri, United States

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health; 🇺🇸 New York, New York, United States

UPMC Hillman Cancer Center; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Colorado Cancer Center; 🇺🇸 Aurora, Colorado, United States

Thomas Jefferson University; 🇺🇸 Philadelphia, Pennsylvania, United States