Solid Tumor, AML Adult Clinical Trial
Official title:
Phase 1/2 Study of RTX-240 Monotherapy and in Combination With Pembrolizumab
| Verified date | December 2022 |
| Source | Rubius Therapeutics |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Interventional |
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).
| Status | Terminated |
| Enrollment | 69 |
| Est. completion date | November 30, 2022 |
| Est. primary completion date | November 30, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years and older |
| Eligibility | 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) |
| Country | Name | City | State |
|---|---|---|---|
| United States | Massachusetts General Hospital | Boston | Massachusetts |
| United States | Sarah Cannon Research Institute/ Colorado Blood Cancer Institute | Denver | Colorado |
| United States | Virginia Cancer Specialists | Fairfax | Virginia |
| United States | University of California San Diego | La Jolla | California |
| United States | The Angeles Clinic & Research Institute | Los Angeles | California |
| United States | Sylvester Comprehensive Cancer Center/UMHC | Miami | Florida |
| United States | Sarah Cannon Research Institute | Nashville | Tennessee |
| United States | Columbia University Medical Center | New York | New York |
| United States | Thomas Jefferson University | Philadelphia | Pennsylvania |
| United States | UPMC Hillman Cancer Center | Pittsburgh | Pennsylvania |
| United States | Oregon Health & Sciences University - Knight Cancer Institute | Portland | Oregon |
| Lead Sponsor | Collaborator |
|---|---|
| Rubius Therapeutics |
United States,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Primary | Safety Assessment: Measured by incidence of Treatment Emergent Adverse Events (TEAEs) | Up to 38 months | ||
| Primary | Dose limiting toxicities (DLTs) of study treatment as determined by incidence and severity of adverse events (AEs) | Up to 38 months | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | 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 | ||
| Secondary | Anti-tumor activity of study treatment measured by duration of response (DoR) | Up to 38 months | ||
| Secondary | Anti-tumor activity of study treatment measured by progression free survival (PFS) | Up to 38 months | ||
| Secondary | Anti-tumor activity of study treatment measured by overall survival (OS) | Up to 38 months | ||
| Secondary | Anti-tumor activity of study treatment measured by time to response (TTR). | Up to 38 months | ||
| Secondary | Anti-tumor activity of study treatment measured by time to progression (TTP) | Up to 38 months | ||
| Secondary | Anti-Tumor activity of study treatment Measured by Objective Response Rate (ORR) | Up to 38 months | ||
| Secondary | Proportion of AML patients with CR, CR with incomplete recovery (CRi), morphologic leukemia-free state, or PR | Up to 38 months |