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RTX-321 Monotherapy in Patients With HPV 16+ Tumors

Sponsor
Rubius Therapeutics (Industry)
Overall Status
Active, not recruiting
CT.gov ID
NCT04672980
Collaborator
(none)
9
Enrollment
10
Locations
2
Arms
29.2
Anticipated Duration (Months)
0.9
Patients Per Site
0
Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 1

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 Design

Study Type:
Interventional
Actual Enrollment :
9 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1 Study of RTX-321 for the Treatment of Patients With Advanced Malignancies Associated With Human Papillomavirus-16 Infection
Actual Study Start Date :
Apr 8, 2021
Anticipated Primary Completion Date :
Aug 15, 2023
Anticipated Study Completion Date :
Sep 15, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

  1. Safety Assessment by rate of Adverse Events: [up to 30 months]

    Measured by incidence of Treatment Emergent Adverse Events (TEAEs)

  2. Dose limiting toxicities (DLTs) of RTX-321: [up to 30 months]

    As determined by incidence and severity of adverse events (AEs)

Secondary Outcome Measures

  1. 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

  2. Pharmacokinetics (PK) of RTX-321: [up to 30 months]

    As measured by the detection of the number of RTX-321 cells using flow cytometry

  3. Anti-tumor activity of RTX-321 [up to 30 months]

    measured by duration of response (DoR)

  4. Anti-tumor activity of RTX-321 [up to 30 months]

    Measured by overall survival (OS)

  5. Anti-tumor activity of RTX-321 [up to 30 months]

    Measured by progression free survival (PFS)

  6. Anti-tumor activity of RTX-321 [up to 30 months]

    Measured by overall response rate (ORR)

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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).

Contacts and Locations

Locations

Site City State Country Postal Code
1 University of Alabama Birmingham Alabama United States 35249
2 The Angeles Clinic & Research Institute Los Angeles California United States 90025
3 University of Colorado Cancer Center Aurora Colorado United States 80045
4 Washington University Saint Louis Missouri United States 63110
5 Laura & Isaac Perlmutter Cancer Center at NYU Langone Health New York New York United States 10016
6 OU Health Stephenson Cancer Center Oklahoma City Oklahoma United States 73104
7 Thomas Jefferson University Philadelphia Pennsylvania United States 19107
8 UPMC Hillman Cancer Center Pittsburgh Pennsylvania United States 15232
9 Sarah Cannon Research Institute Nashville Tennessee United States 37203
10 Virginia Cancer Specialists Fairfax Virginia United States 22031

Sponsors and Collaborators

  • Rubius Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Rubius Therapeutics
ClinicalTrials.gov Identifier:
NCT04672980
Other Study ID Numbers:
  • RTX-321-01
First Posted:
Dec 17, 2020
Last Update Posted:
May 25, 2022
Last Verified:
Jan 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:
Anus Neoplasms

Study Results

No Results Posted as of May 25, 2022