RTX-321 Monotherapy in Patients With HPV 16+ Tumors

NCT04672980 | Terminated Phase 1 FDA Drug

• 1 other identifier: RTX-321-01
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 10

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.

Conditions

Cervical Cancer; Head and Neck Cancer; Anal Cancer

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (6)

• Pharmacodynamics (PD) of RTX-321:

  up to 30 months

• Pharmacokinetics (PK) of RTX-321:

  up to 30 months

• Anti-tumor activity of RTX-321

  up to 30 months

• Anti-tumor activity of RTX-321

  up to 30 months

• Anti-tumor activity of RTX-321

  up to 30 months

Study Arms (2)

RTX-321 Dose Escalation

EXPERIMENTAL

Phase 1: RTX-321 administered intravenously on Day 1 of each cycle monotherapy dose escalation

Drug: RTX-321

RTX-321 Dose Expansion

EXPERIMENTAL

Phase 1: RTX-321 administered intravenously on Day 1 of each cycle.

Drug: RTX-321

Interventions

RTX-321 DRUG

RTX-321 monotherapy

RTX-321 Dose Escalation; RTX-321 Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• Rubius Therapeutics: lead

Study Sites (10)

University of Alabama

Birmingham, Alabama, 35249, United States

Location

The Angeles Clinic & Research Institute

Los Angeles, California, 90025, United States

Location

University of Colorado Cancer Center

Aurora, Colorado, 80045, United States

Location

Washington University

St Louis, Missouri, 63110, United States

Location

Laura & Isaac Perlmutter Cancer Center at NYU Langone Health

New York, New York, 10016, United States

Location

OU Health Stephenson Cancer Center

Oklahoma City, Oklahoma, 73104, United States

Location

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

Location

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, 15232, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

Virginia Cancer Specialists

Fairfax, Virginia, 22031, United States

Location

MeSH Terms

Conditions

Uterine Cervical Neoplasms; Head and Neck Neoplasms; Anus Neoplasms

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Rectal Neoplasms; Colorectal Neoplasms; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Diseases; Anus Diseases; Rectal Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 8, 2020
• First Posted: December 17, 2020
• Study Start: April 8, 2021
• Primary Completion: November 30, 2022
• Study Completion: November 30, 2022
• Last Updated: December 8, 2022

Record last verified: 2022-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (10)