RTX-224 Monotherapy in Patients With Solid Tumors

A Phase 1/2 Study of RTX-224 for the Treatment of Patients With Advanced Solid Tumors

This is an open-label, multidose, first-in-human (FIH), Phase 1/2 study of RTX-224 for the treatment of patients with relapsed or refractory (R/R), or locally advanced solid tumors.

Study Overview

• Status: Terminated
• Conditions: Non Small Cell Lung Cancer; Head and Neck Squamous Cell Carcinoma; Urothelial Carcinoma; Cutaneous Melanoma; TNBC - Triple-Negative Breast Cancer
• Intervention / Treatment: Drug: RTX-224

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-224 in adult patients with persistent, recurrent, or metastatic, unresectable solid tumors. The study will include a monotherapy dose escalation phase followed by an expansion phase.

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Arizona
    • Scottsdale, Arizona, United States, 85258
      • HonorHealth
  • California
    • Los Angeles, California, United States, 90033
      • USC Norris Comprehensive Cancer Center
    • San Francisco, California, United States, 94143
      • University of California San Francisco Health
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Sarah Cannon Research Institute
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Virginia Cancer Specialists

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Signed written informed consent obtained prior to study procedures Patients ≥18 years with an ECOG of 0 or 1

• R/R, or locally advanced, unresectable, and histologically or cytologically confirmed

  (a) NSCLC, (b) cutaneous melanoma, (c) HNSCC, (d) UC, or (e) TNBC, which are refractory to or otherwise ineligible for treatment with standard-of-care treatments

• Prior therapy in each disease setting must include the following:

  • NSCLC: Patients must have experienced disease progression following platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. Patients with EGFR, ALK, ROS-1, or other actionable mutations should have previously received or been ineligible for therapies targeting their respective mutation(s).
  • Cutaneous melanoma: Patients must have experienced disease progression following a PD-1 or PD-L1 inhibitor. Patients with V600E mutations should have previously received or been ineligible for approved BRAF inhibitor or MEK inhibitor therapy.
  • HNSCC: Patients must have experienced disease progression following platinum-based combination chemotherapy and a PD-1 or PD-L1 inhibitor.
  • UC: Patients must have experienced disease progression following platinum-based combination chemotherapy and a PD-1 or PD-L1 inhibitor.
  • TNBC: Patients must have experienced disease progression following single-agent or combination chemotherapy. Patients with BRCA1/2 mutations should have previously received or been ineligible for an approved PARP inhibitor; patients who are PD-L1 positive should have received or been ineligible for an approved PD-1 or PD-L1 inhibitor.
• 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
  • Platelet count ≥100 × 103/μL
  • Hemoglobin ≥9 g/dL

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: RTX-224 Dose Escalation; Phase 1: RTX-224 monotherapy dose escalation in Solid Tumors, administered intravenously on Day 1 of each cycle.	Drug: RTX-224; RTX-224 monotherapy
Experimental: RTX-224 Dose Expansion; Phase 2: RTX-224 monotherapy dose expansion in Solid Tumors, administered intravenously on Day 1 of each cycle.	Drug: RTX-224; RTX-224 monotherapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety Assessment by rate of Adverse Events (AEs)	Measured by incidence of Treatment Emergent Adverse Events (TEAEs)	up to 30 months
Dose limiting toxicities (DLTs) of RTX-224	As determined by incidence and severity of adverse events	up to 30 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pharmacodynamics (PD) of RTX-224	As measured by the changes in immune cell populations, e.g., T cells and NK cells	up to 30 months
Pharmacokinetics (PK) of RTX-224	Maximum concentration (Cmax) of RTX-224 cells (positive for both 4-1BBL and IL-12 using flow cytometry) in blood after administration will be measured.	up to 30 months
Pharmacokinetics (PK) of RTX-224	Time to maximum concentration (tmax) of RTX-224 cells (positive for both 4-1BBL and IL-12 using flow cytometry) in blood after administration will be measured.	up to 30 months
Anti-tumor activity of RTX-224	As measured by duration of response (DoR)	up to 30 months
Anti-tumor activity of RTX-224	As measured by overall survival (OS)	up to 30 months
Anti-tumor activity of RTX-224	As measured by progression free survival (PFS)	up to 30 months
Anti-tumor activity of RTX-224	As measured by disease control rate (DCR)	up to 30 months
Anti-tumor activity of RTX-224	As measured by objective response rate (ORR)	up to 30 months

Collaborators and Investigators

• Sponsor: Rubius Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): January 12, 2022
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: January 6, 2022
• First Submitted That Met QC Criteria: January 28, 2022
• First Posted (Actual): February 2, 2022

Study Record Updates

• Last Update Posted (Estimate): December 9, 2022
• Last Update Submitted That Met QC Criteria: December 7, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: Solid Tumor, Advanced Solid Tumors
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms by Histologic Type; Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Breast Diseases; Head and Neck Neoplasms; Carcinoma, Squamous Cell; Breast Neoplasms; Carcinoma; Squamous Cell Carcinoma of Head and Neck; Triple Negative Breast Neoplasms
• Other Study ID Numbers: RTX-224-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No