RTX-240 Monotherapy and in Combination With Pembrolizumab

• ClinicalTrials.gov Identifier: NCT04372706
• Recruitment Status: Terminated
• First Posted: May 4, 2020
• Last Update Posted: December 13, 2022
• Sponsor: Rubius Therapeutics
• Information provided by (Responsible Party): Rubius Therapeutics

Study Description

Brief Summary:

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).

Condition or disease	Intervention/treatment	Phase
Solid Tumor, AML Adult	Drug: RTX-240; Drug: Pembrolizumab	Phase 1; Phase 2

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 69 participants
• Allocation: Non-Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Phase 1/2 Study of RTX-240 Monotherapy and in Combination With Pembrolizumab
• Actual Study Start Date: May 6, 2020
• Actual Primary Completion Date: November 30, 2022
• Actual Study Completion Date: November 30, 2022

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

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

Secondary Outcome Measures :

1. PK of study treatment as measured by detection of the number of 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 ]
2. Determination of the Immunogenicity of study treatment 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 ]
3. Anti-tumor activity of study treatment measured by clinical benefit rate (CBR) (% of patients who achieve CR, PR or stable disease [SD]) [ Time Frame: Up to 38 months ]
4. Anti-tumor activity of study treatment measured by duration of response (DoR) [ Time Frame: Up to 38 months ]
5. Anti-tumor activity of study treatment measured by progression free survival (PFS) [ Time Frame: Up to 38 months ]
6. Anti-tumor activity of study treatment measured by overall survival (OS) [ Time Frame: Up to 38 months ]
7. Anti-tumor activity of study treatment measured by time to response (TTR). [ Time Frame: Up to 38 months ]
8. Anti-tumor activity of study treatment measured by time to progression (TTP) [ Time Frame: Up to 38 months ]
9. Anti-Tumor activity of study treatment Measured by Objective Response Rate (ORR) [ Time Frame: Up to 38 months ]
10. Proportion of AML patients with CR, CR with incomplete recovery (CRi), morphologic leukemia-free state, or PR [ Time Frame: Up to 38 months ]

Eligibility Criteria

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

Criteria

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)

Contacts and Locations

Locations

United States, California

University of California San Diego

La Jolla, California, United States, 92093

The Angeles Clinic & Research Institute

Los Angeles, California, United States, 90025

United States, Colorado

Sarah Cannon Research Institute/ Colorado Blood Cancer Institute

Denver, Colorado, United States, 80218

United States, Florida

Sylvester Comprehensive Cancer Center/UMHC

Miami, Florida, United States, 33136

United States, Massachusetts

Massachusetts General Hospital

Boston, Massachusetts, United States, 02114

United States, New York

Columbia University Medical Center

New York, New York, United States, 10032

United States, Oregon

Oregon Health & Sciences University - Knight Cancer Institute

Portland, Oregon, United States, 97239

United States, Pennsylvania

Thomas Jefferson University

Philadelphia, Pennsylvania, United States, 19107

UPMC Hillman Cancer Center

Pittsburgh, Pennsylvania, United States, 15232

United States, Tennessee

Sarah Cannon Research Institute

Nashville, Tennessee, United States, 37203

United States, Virginia

Virginia Cancer Specialists

Fairfax, Virginia, United States, 22031

Sponsors and Collaborators

Rubius Therapeutics

More Information

• Responsible Party: Rubius Therapeutics
• ClinicalTrials.gov Identifier: NCT04372706
• Other Study ID Numbers: RTX-240-01
• First Posted: May 4, 2020
• Last Update Posted: December 13, 2022
• Last Verified: December 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Pembrolizumab; Antineoplastic Agents, Immunological; Antineoplastic Agents