RTX-240 Monotherapy and in Combination With Pembrolizumab

December 9, 2022 updated by: Rubius Therapeutics

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

Status

Indicates the current recruitment status or the expanded access status.
Terminated

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
69

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Safety Assessment: Measured by incidence of Treatment Emergent Adverse Events (TEAEs)
Time Frame: Up to 38 months
Up to 38 months
Dose limiting toxicities (DLTs) of study treatment as determined by incidence and severity of adverse events (AEs)
Time Frame: Up to 38 months
Up to 38 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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.
Time Frame: Assessed From the 1st dose of RTX-240 until 30 days after last of study treatment
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
Time Frame: Assessed From the 1st dose of RTX-240 until 30 days after last of study treatment
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])
Time Frame: Up to 38 months
Up to 38 months
Anti-tumor activity of study treatment measured by duration of response (DoR)
Time Frame: Up to 38 months
Up to 38 months
Anti-tumor activity of study treatment measured by progression free survival (PFS)
Time Frame: Up to 38 months
Up to 38 months
Anti-tumor activity of study treatment measured by overall survival (OS)
Time Frame: Up to 38 months
Up to 38 months
Anti-tumor activity of study treatment measured by time to response (TTR).
Time Frame: Up to 38 months
Up to 38 months
Anti-tumor activity of study treatment measured by time to progression (TTP)
Time Frame: Up to 38 months
Up to 38 months
Anti-Tumor activity of study treatment Measured by Objective Response Rate (ORR)
Time Frame: Up to 38 months
Up to 38 months
Proportion of AML patients with CR, CR with incomplete recovery (CRi), morphologic leukemia-free state, or PR
Time Frame: Up to 38 months
Up to 38 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Rubius Therapeutics

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
May 6, 2020

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
November 30, 2022

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
November 30, 2022

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 23, 2020

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 29, 2020

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 4, 2020

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 13, 2022

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 9, 2022

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2022

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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