RTX-240 Monotherapy and in Combination With Pembrolizumab

Phase 1/2 Study of RTX-240 Monotherapy and in Combination With Pembrolizumab

Open label, multicenter, multidose, first-in-human Phase 1/2 study of RTX-240 monotherapy or in combination of pembrolizumab for the treatment of patients with (1) relapsed/refractory R/R or locally advanced solid tumors (Phase 1/2) or (2) R/R Acute Myeloid Leukemia (AML) (Phase 1 only).

Study Overview

• Status: Terminated
• Conditions: Solid Tumor, AML Adult
• Intervention / Treatment: Drug: RTX-240; Drug: Pembrolizumab

Detailed Description

This is a Phase 1/2, open label, multicenter, multidose, first-in-human (FIH) dose escalation and expansion study 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 (R/R) or locally advanced solid tumors (Phase 1/2) or R/R acute myeloid leukemia (Phase 1 only), and RTX-240 in combination with pembrolizumab in adult patients with R/R or locally advanced solid tumors (Phase 1 only). 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 stimulating the innate and adaptive immune systems for the treatment of cancer. The study includes a monotherapy dose escalation phase (Phase 1) followed by an expansion phase (Phase 2) in specified tumor types.

• Study Type: Interventional
• Enrollment (Actual): 69
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California San Diego
    • Los Angeles, California, United States, 90025
      • The Angeles Clinic & Research Institute
  • Colorado
    • Denver, Colorado, United States, 80218
      • Sarah Cannon Research Institute/ Colorado Blood Cancer Institute
  • Florida
    • Miami, Florida, United States, 33136
      • Sylvester Comprehensive Cancer Center/UMHC
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Massachusetts General Hospital
  • New York
    • New York, New York, United States, 10032
      • Columbia University Medical Center
  • Oregon
    • Portland, Oregon, United States, 97239
      • Oregon Health & Sciences University - Knight Cancer Institute
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Thomas Jefferson University
    • Pittsburgh, Pennsylvania, United States, 15232
      • UPMC Hillman Cancer Center
  • 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 0 or 1 (Parts 1, 2 and 4) or 0-2 (Part 3).
• Relapsed/Refractory (R/R) or locally advanced, unresectable solid tumor for which no standard therapy exists (Parts 1, 2 and 4), or for which the patient is ineligible or has declined standard therapy or R/R, cytologically confirmed AML (Part 3).
• 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 and Blood Cell Counts (Parts 1, 2, and 4) 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 ≥ 1 × 10^3/μL without myeloid growth factor support for at least one week prior to enrollment
  • Platelet count ≥ 75 × 10^3/μL
  • Hemoglobin should be ≥ 9 g/dL without red blood cell transfusion for at least one week
  • Patients must have LVEF ≥ 45%
• Patients enrolling into Part 2 of the study must be diagnosed with NSCLC, RCC, or anal cancers
• Patients enrolling into Part 4 must be diagnosed with NSCLC or RCC
• Patients enrolling into either Part 2 or 4 must have 2 or fewer prior treatment regimens. If patient received a prior PD-1/PD-L1-containing regimen, a prior response is required.

Exclusion Criteria:

• Primary central nervous system (CNS) malignancy or CNS involvement, unless asymptomatic, previously treated, and stable without steroids (Parts 1, 2 and 4) or known CNS leukemia (Part 3).
• 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
• Class III or IV cardiomyopathy per the New York Heart Association criteria
• Leukemic blast count ≥ 25 x 10^3/µL (Part 3)
• Concomitant conditions requiring active immunosuppression
• History of clinically significant Grade 3 or higher immune related Adverse Event (irAE)
• Prior malignancy within the past 3 years, with protocol specified exceptions
• History of severe hypersensitivity to a PD-1/PD-L1 blocking Ab unless previously rechallenged successfully (Part 4)
• Current noninfectious pneumonitis or a history of radiation pneumonitis or pneumonitis that required steroids, or Grade 2 or greater immune related pneumonitis, hepatitis, hypophysitis, or other endocrinopathy (Part 4)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: RTX-240 Dose Escalation; Phase 1: RTX-240 monotherapy dose escalation in Solid Tumors	Drug: RTX-240; Engineered red cells co-expressing 4-1BBL and IL-15TP
Experimental: Part 2: RTX-240 Solid Tumor Expansion; Phase 2: RTX-240 monotherapy dose expansion in Non-small Cell Lung Cancer (NSCLC), Renal Cell Carcinoma (RCC), and anal cancers	Drug: RTX-240; Engineered red cells co-expressing 4-1BBL and IL-15TP
Experimental: Part 3: RTX-240 Dose Escalation; Phase 1: RTX-240 monotherapy dose escalation in AML	Drug: RTX-240; Engineered red cells co-expressing 4-1BBL and IL-15TP
Experimental: Part 4: RTX-240 Plus Pembrolizumab Dose Escalation; Phase 1: RTX-240 dose escalation in combination with Pembrolizumab in Solid Tumors	Drug: RTX-240; Engineered red cells co-expressing 4-1BBL and IL-15TP; Drug: Pembrolizumab; Humanized immunoglobulin G4 programmed death receptor-1 blocking antibody

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety Assessment: Measured by incidence of Treatment Emergent Adverse Events (TEAEs)	Up to 38 months
Dose limiting toxicities (DLTs) of study treatment as determined by incidence and severity of adverse events (AEs)	Up to 38 months

Secondary Outcome Measures

Outcome Measure	Time Frame
PK of study treatment as measured by detection of the number of cells positive for both 4-1BBL and IL-15 using flow cytometry.	Assessed From the 1st dose of RTX-240 until 30 days after last of study treatment
Determination of the Immunogenicity of study treatment Measured by the incidence of antibodies to RTX-240	Assessed From the 1st dose of RTX-240 until 30 days after last of study treatment
Anti-tumor activity of study treatment measured by clinical benefit rate (CBR) (% of patients who achieve CR, PR or stable disease [SD])	Up to 38 months
Anti-tumor activity of study treatment measured by duration of response (DoR)	Up to 38 months
Anti-tumor activity of study treatment measured by progression free survival (PFS)	Up to 38 months
Anti-tumor activity of study treatment measured by overall survival (OS)	Up to 38 months
Anti-tumor activity of study treatment measured by time to response (TTR).	Up to 38 months
Anti-tumor activity of study treatment measured by time to progression (TTP)	Up to 38 months
Anti-Tumor activity of study treatment Measured by Objective Response Rate (ORR)	Up to 38 months
Proportion of AML patients with CR, CR with incomplete recovery (CRi), morphologic leukemia-free state, or PR	Up to 38 months

Collaborators and Investigators

• Sponsor: Rubius Therapeutics

Study record dates

Study Major Dates

• Study Start (Actual): May 6, 2020
• Primary Completion (Actual): November 30, 2022
• Study Completion (Actual): November 30, 2022

Study Registration Dates

• First Submitted: April 23, 2020
• First Submitted That Met QC Criteria: April 29, 2020
• First Posted (Actual): May 4, 2020

Study Record Updates

• Last Update Posted (Estimate): December 13, 2022
• Last Update Submitted That Met QC Criteria: December 9, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Antineoplastic Agents; Antineoplastic Agents, Immunological; Pembrolizumab
• Other Study ID Numbers: RTX-240-01

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