Clinical Trials /

RTX-321 Monotherapy in Patients With HPV 16+ Tumors

NCT04672980

Description:

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.

Related Conditions:
  • Anal Canal Squamous Cell Carcinoma
  • Cervical Carcinoma
  • Head and Neck Squamous Cell Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: RTX-321 Monotherapy in Patients With HPV 16+ Tumors
  • Official Title: A Phase 1 Study of RTX-321 for the Treatment of Patients With Advanced Malignancies Associated With Human Papillomavirus-16 Infection

Clinical Trial IDs

  • ORG STUDY ID: RTX-321-01
  • NCT ID: NCT04672980

Conditions

  • Cervical Cancer
  • Head and Neck Cancer
  • Anal Cancer

Interventions

DrugSynonymsArms
RTX-321RTX-321 Dose Escalation

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
RTX-321 Dose EscalationExperimentalPhase 1: RTX-321 administered intravenously on Day 1 of each cycle monotherapy dose escalation
  • RTX-321
RTX-321 Dose ExpansionExperimentalPhase 1: RTX-321 administered intravenously on Day 1 of each cycle.
  • RTX-321

Eligibility Criteria

        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).
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Safety Assessment by rate of Adverse Events:
Time Frame:up to 30 months
Safety Issue:
Description:Measured by incidence of Treatment Emergent Adverse Events (TEAEs)

Secondary Outcome Measures

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

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Rubius Therapeutics

Last Updated

December 17, 2020