Solid Tumor, AML Adult
Conditions
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).
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.
Interventions
DRUGRTX-240
Engineered red cells co-expressing 4-1BBL and IL-15TP
DRUGPembrolizumab
Humanized immunoglobulin G4 programmed death receptor-1 blocking antibody
Sponsors
Rubius Therapeutics
Study design
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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)
Design outcomes
Primary
| 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
| Measure | Time frame |
|---|---|
| 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 |
| 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 |
| 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 |
| Anti-tumor activity of study treatment measured by time to response (TTR). | Up to 38 months |
| 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 |
Countries
United States
Outcome results
None listed