RTX-240 Monotherapy and in Combination With Pembrolizumab

Sponsor

Rubius Therapeutics (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04372706

Collaborator

(none)

166

Enrollment

Locations

Arms

42.8

Anticipated Duration (Months)

15.1

Patients Per Site

0.4

Patients Per Site Per Month

Study Details

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

Anticipated Enrollment :

166 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

Anticipated Primary Completion Date :

Jul 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

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

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 Outcome Measures

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]
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]
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]
Anti-tumor activity of study treatment measured by time to response (TTR). [Up to 38 months]
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

	Site	City	State	Country	Postal Code
1	University of California San Diego	La Jolla	California	United States	92093
2	The Angeles Clinic & Research Institute	Los Angeles	California	United States	90025
3	Sarah Cannon Research Institute/ Colorado Blood Cancer Institute	Denver	Colorado	United States	80218
4	Sylvester Comprehensive Cancer Center/UMHC	Miami	Florida	United States	33136
5	Massachusetts General Hospital	Boston	Massachusetts	United States	02114
6	Columbia University Medical Center	New York	New York	United States	10032
7	Oregon Health & Sciences University - Knight Cancer Institute	Portland	Oregon	United States	97239
8	Thomas Jefferson University	Philadelphia	Pennsylvania	United States	19107
9	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania	United States	15232
10	Sarah Cannon Research Institute	Nashville	Tennessee	United States	37203
11	Virginia Cancer Specialists	Fairfax	Virginia	United States	22031

Sponsors and Collaborators

Rubius Therapeutics

Investigators

None specified.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Rubius Therapeutics

ClinicalTrials.gov Identifier:

NCT04372706

Other Study ID Numbers:

RTX-240-01

First Posted:

May 4, 2020

Last Update Posted:

Apr 19, 2022

Last Verified:

Apr 1, 2022

Individual Participant Data (IPD) Sharing Statement:

Plan to Share IPD:

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Additional relevant MeSH terms:

Pembrolizumab

Study Results

No Results Posted as of Apr 19, 2022