RTX-321 Monotherapy in Patients With HPV 16+ Tumors

Head and Neck Cancer Clinical Trial

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 Details — Status: Terminated

Administrative data

• NCT number: NCT04672980
• Other study ID #: RTX-321-01
• Status: Terminated
• Phase: Phase 1
• Start date: April 8, 2021
• Est. completion date: November 30, 2022

Study information

• Verified date: December 2022
• Source: Rubius Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 9
• Est. completion date: November 30, 2022
• Est. primary completion date: November 30, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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).

Related Conditions & MeSH terms

• Anal Cancer
• Anus Neoplasms
• Cervical Cancer
• Head and Neck Cancer

Intervention

Drug:
• RTX-321
RTX-321 monotherapy

Locations

Country	Name	City	State
United States	University of Colorado Cancer Center	Aurora	Colorado
United States	University of Alabama	Birmingham	Alabama
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	The Angeles Clinic & Research Institute	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	Laura & Isaac Perlmutter Cancer Center at NYU Langone Health	New York	New York
United States	OU Health Stephenson Cancer Center	Oklahoma City	Oklahoma
United States	Thomas Jefferson University	Philadelphia	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	Washington University	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
Rubius Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Assessment by rate of Adverse Events:	Measured by incidence of Treatment Emergent Adverse Events (TEAEs)	up to 30 months
Primary	Dose limiting toxicities (DLTs) of RTX-321:	As determined by incidence and severity of adverse events (AEs)	up to 30 months
Secondary	Pharmacodynamics (PD) of RTX-321:	As measured by the changes in number of CD8+ T-cells in peripheral blood using flow cytometry	up to 30 months
Secondary	Pharmacokinetics (PK) of RTX-321:	As measured by the detection of the number of RTX-321 cells using flow cytometry	up to 30 months
Secondary	Anti-tumor activity of RTX-321	measured by duration of response (DoR)	up to 30 months
Secondary	Anti-tumor activity of RTX-321	Measured by overall survival (OS)	up to 30 months
Secondary	Anti-tumor activity of RTX-321	Measured by progression free survival (PFS)	up to 30 months
Secondary	Anti-tumor activity of RTX-321	Measured by overall response rate (ORR)	up to 30 months