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RTX-321 Monotherapy in Patients With HPV 16+ Tumors

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ClinicalTrials.gov Identifier: NCT04672980
Recruitment Status : Recruiting
First Posted : December 17, 2020
Last Update Posted : December 17, 2020
Sponsor:
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Cervical Cancer Head and Neck Cancer Anal Cancer Drug: RTX-321 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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 63 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
Estimated Study Start Date : January 2, 2021
Estimated Primary Completion Date : August 15, 2023
Estimated Study Completion Date : September 15, 2023

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Safety Assessment by rate of Adverse Events: [ Time Frame: up to 30 months ]
    Measured by incidence of Treatment Emergent Adverse Events (TEAEs)

  2. Dose limiting toxicities (DLTs) of RTX-321: [ Time Frame: up to 30 months ]
    As determined by incidence and severity of adverse events (AEs)


Secondary Outcome Measures :
  1. Pharmacodynamics (PD) of RTX-321: [ Time Frame: 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: [ Time Frame: 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 [ Time Frame: up to 30 months ]
    measured by duration of response (DoR)

  4. Anti-tumor activity of RTX-321 [ Time Frame: up to 30 months ]
    Measured by overall survival (OS)

  5. Anti-tumor activity of RTX-321 [ Time Frame: up to 30 months ]
    Measured by progression free survival (PFS)

  6. Anti-tumor activity of RTX-321 [ Time Frame: up to 30 months ]
    Measured by overall response rate (ORR)



Information from the National Library of Medicine

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04672980


Contacts
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Contact: Christina Coughlin, M.D., Ph.D. 617-679-9600 chris.coughlin@rubiustx.com

Locations
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United States, Tennessee
Sarah Cannon Research Institute Recruiting
Nashville, Tennessee, United States, 37203
Contact: Sarah Cannon Research Site    615-329-7478    CANN.ResearchReferrals@scresearch.net   
Sponsors and Collaborators
Rubius Therapeutics
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Responsible Party: Rubius Therapeutics
ClinicalTrials.gov Identifier: NCT04672980    
Other Study ID Numbers: RTX-321-01
First Posted: December 17, 2020    Key Record Dates
Last Update Posted: December 17, 2020
Last Verified: December 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Anus Neoplasms
Neoplasms by Site
Neoplasms
Rectal Neoplasms
Colorectal Neoplasms
Intestinal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Gastrointestinal Diseases
Intestinal Diseases
Anus Diseases
Rectal Diseases