RTX-240 Monotherapy

Overview

Open label, multicenter, multidose, first-in-human Phase 1/2 study of RTX-240 for the treatment of patients with relapsed/refractory or locally advanced solid tumors.

Full Title of Study: “Phase 1/2 Study of RTX-240 Monotherapy”

Study Type

  • Study Type: Interventional
  • Study Design
    • Allocation: Non-Randomized
    • Intervention Model: Parallel Assignment
    • Primary Purpose: Treatment
    • Masking: None (Open Label)
  • Study Primary Completion Date: January 2023

Detailed Description

This is a Phase 1/2, open label, multicenter, multidose, first-in-human (FIH) dose escalation and expansion to determine the safety and tolerability, recommended phase 2 dose and optimal dosing interval, pharmacology, and antitumor activity of RTX-240 in adult patients with relapsed/refractory or locally advanced solid tumors. RTX-240 is a cellular therapy that co-expresses 4-1BBL and IL-15TP, a fusion of IL-15 and IL-15 receptor alpha, 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 in specified tumor types.

Interventions

  • Drug: RTX-240
    • Engineered red cells co-expressing 4-1BBL and IL-15TP

Arms, Groups and Cohorts

  • Experimental: Part 1: RTX-240 Dose Escalation
    • Phase 1: RTX-240 administered intravenously on Day 1 of each cycle.
  • Experimental: Part 2: RTX-240 Solid Tumor Expansion
    • Phase 2: RTX-240 administered intravenously on Day 1 of each cycle.

Clinical Trial Outcome Measures

Primary Measures

  • Safety Assessment: Measured by incidence of Treatment Emergent Adverse Events (TEAEs)
    • Time Frame: Up to 38 months
  • Dose limiting toxicities (DLTs) of RTX-240 as determined by incidence and severity of adverse events (AEs)
    • Time Frame: Up to 38 months
  • Pharmacodynamics (PD) of RTX-240 will be evaluated through changes in NK cell number relative to baseline
    • Time Frame: Up to 38 months
  • Pharmacodynamics (PD) of RTX-240 will be evaluated through changes in T-cell number relative to baseline
    • Time Frame: Up to 38 months
  • Anti-Tumor activity of RTX-240 Measured by Overall Response Rate (ORR)
    • Time Frame: Up to 38 months

Secondary Measures

  • PK of RTX-240 as measured by detection of the number of RTX cells positive for both 4-1BBL and IL-15 using flow cytometry.
    • Time Frame: Assessed From the 1st dose of RTX-240 until 30 days after last of study treatment
  • Determination of the Immunogenicity of RTX-240 Measured by the incidence of antibodies to RTX-240
    • Time Frame: Assessed From the 1st dose of RTX-240 until 30 days after last of study treatment
  • Anti-tumor activity of RTX-240 measured by clinical benefit rate (CBR) (% of patients who achieve CR, PR or SD)
    • Time Frame: Up to 38 months
  • Anti-tumor activity of RTX-240 measured by duration of response (DoR)
    • Time Frame: Up to 38 months
  • Anti-tumor activity of RTX-240 measured by progression free survival (PFS)
    • Time Frame: Up to 38 months
  • Anti-tumor activity of RTX-240 measured by overall survival (OS)
    • Time Frame: Up to 38 months
  • Anti-tumor activity of RTX-240 measured by time to response (TTR).
    • Time Frame: Up to 38 months
  • Anti-tumor activity of RTX-240 measured by time to progression (TTP)
    • Time Frame: Up to 38 months

Participating in This Clinical Trial

Inclusion Criteria

  • Signed written informed consent obtained prior to study procedures
  • Patients ≥18 years with an ECOG 0 or 1.
  • Relapsed/Refractory or locally advanced, unresectable solid tumor for which no standard therapy exists, or for which the patient is ineligible or has declined standard therapy.
  • 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.
  • Positive antibody screen using institution's standard type and screen test
  • Adequate Organ Function as Defined by the protocol:
  • GFR ≥ 50 mL/min/1.73,
  • AST and ALT ≤ 3 × the ULN and total bilirubin ≤ 1.5 × ULN,
  • In the absence of cancer within the liver, or AST and ALT ≤ 5 × ULN and total bilirubin ≤ 3 × ULN, in the setting of primary or metastatic liver tumors.
  • ANC ≥ 10 × 103/μL and platelet count ≥ 100 × 103/μL without myeloid growth factor support or transfusion, respectively, for at least one week.
  • Hemoglobin should be ≥ 9 g/dL without red blood cell transfusion for at least two weeks.
  • Patients must have LVEF ≥ 45%
  • Patients enrolling into Part 2 of the study must be diagnosed with a solid tumor that has been selected for an expansion cohort

Exclusion Criteria

  • Primary CNS malignancy or central nervous system (CNS) involvement, unless asymptomatic, previously treated, and stable without steroids.
  • 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).
  • Clinically significant coagulopathy, uncontrolled hypertension or autoimmune hemolytic anemia
  • Concomitant conditions requiring active immunosuppression
  • Grade 3 immune related Adverse Event (irAE)
  • Prior malignancy within the past 3 years, with protocol specified exceptions

Gender Eligibility: All

Minimum Age: 18 Years

Maximum Age: N/A

Are Healthy Volunteers Accepted: No

Investigator Details

  • Lead Sponsor
    • Rubius Therapeutics
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Contact(s)
    • Christina Coughlin, M.D., Ph.D., 617-679-9600, chris.coughlin@rubiustx.com

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