Clinical trial NCT04672980: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE1
Conditions: Cervical Cancer
Head and Neck Cancer
Anal Cancer
Lead sponsor: Rubius Therapeutics
Sponsor class: INDUSTRY
First posted: 2020-12-17
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.

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.

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).

Primary outcomes:
measure: Safety Assessment by rate of Adverse Events:
timeFrame: up to 30 months
measure: Dose limiting toxicities (DLTs) of RTX-321:
timeFrame: up to 30 months
Secondary outcomes:
measure: Pharmacodynamics (PD) of RTX-321:
timeFrame: up to 30 months
measure: Pharmacokinetics (PK) of RTX-321:
timeFrame: up to 30 months
measure: Anti-tumor activity of RTX-321
timeFrame: up to 30 months
measure: Anti-tumor activity of RTX-321
timeFrame: up to 30 months
measure: Anti-tumor activity of RTX-321
timeFrame: up to 30 months
measure: Anti-tumor activity of RTX-321
timeFrame: up to 30 months
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama
state: Alabama
city: Los Angeles
country: United States
facility: The Angeles Clinic & Research Institute
state: California
city: Aurora
country: United States
facility: University of Colorado Cancer Center
state: Colorado
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: New York
country: United States
facility: Laura & Isaac Perlmutter Cancer Center at NYU Langone Health
state: New York
city: Oklahoma City
country: United States
facility: OU Health Stephenson Cancer Center
state: Oklahoma
city: Philadelphia
country: United States
facility: Thomas Jefferson University
state: Pennsylvania
city: Pittsburgh
country: United States
facility: UPMC Hillman Cancer Center
state: Pennsylvania
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Fairfax
country: United States
facility: Virginia Cancer Specialists
state: Virginia
Study officials:
References: