Purpose

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

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
All
Accepts Healthy Volunteers
No

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 Design

Phase
Phase 1/Phase 2
Study Type
Interventional
Allocation
Non-Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
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

More Details

Status
Terminated
Sponsor
Rubius Therapeutics

Study Contact

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.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.