RTX-224 Monotherapy in Patients With Solid Tumors

Non Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 1/2 Study of RTX-224 for the Treatment of Patients With Advanced Solid Tumors

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05219578
• Other study ID #: RTX-224-01
• Status: Terminated
• Phase: Phase 1/Phase 2
• Start date: January 12, 2022
• Est. completion date: November 30, 2022

Study information

• Verified date: December 2022
• Source: Rubius Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multidose, first-in-human (FIH), Phase 1/2 study of RTX-224 for the treatment of patients with relapsed or refractory (R/R), or locally advanced solid tumors.

Description:

This is a Phase 1, open label, multicenter, multidose, first-in-human (FIH), dose escalation and expansion to determine the safety and tolerability, recommended phase 2 dose, and pharmacology, and antitumor activity of RTX-224 in adult patients with persistent, recurrent, or metastatic, unresectable solid tumors. The study will include a monotherapy dose escalation phase followed by an expansion phase.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• 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 of 0 or 1

• R/R, or locally advanced, unresectable, and histologically or cytologically confirmed

(a) NSCLC, (b) cutaneous melanoma, (c) HNSCC, (d) UC, or (e) TNBC, which are refractory to or otherwise ineligible for treatment with standard-of-care treatments

• Prior therapy in each disease setting must include the following:

• NSCLC: Patients must have experienced disease progression following platinum-containing chemotherapy and a PD-1 or PD-L1 inhibitor. Patients with EGFR, ALK, ROS-1, or other actionable mutations should have previously received or been ineligible for therapies targeting their respective mutation(s).

• Cutaneous melanoma: Patients must have experienced disease progression following a PD-1 or PD-L1 inhibitor. Patients with V600E mutations should have previously received or been ineligible for approved BRAF inhibitor or MEK inhibitor therapy.

• HNSCC: Patients must have experienced disease progression following platinum-based combination chemotherapy and a PD-1 or PD-L1 inhibitor.

• UC: Patients must have experienced disease progression following platinum-based combination chemotherapy and a PD-1 or PD-L1 inhibitor.

• TNBC: Patients must have experienced disease progression following single-agent or combination chemotherapy. Patients with BRCA1/2 mutations should have previously received or been ineligible for an approved PARP inhibitor; patients who are PD-L1 positive should have received or been ineligible for an approved PD-1 or PD-L1 inhibitor.

• 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 as Defined by the protocol:

• AST and ALT =3 × the upper limit of normal (ULN) Except in documented cases of Gilbert syndrome, total bilirubin =1.5 × ULN

• Serum albumin =2.5 g/dL

• Serum or plasma creatinine =1.5 × ULN and/or glomerular filtration rate =50 mL/min/1.73 calculated by the Cockcroft-Gault formula

• Absolute neutrophil count =1 × 103/µL

• Platelet count =100 × 103/µL

• Hemoglobin =9 g/dL

Exclusion Criteria:

• Patient has central nervous system (CNS) involvement. If the patient fulfills the following 3 criteria, she/he is eligible for the trial after consultation with the Sponsor Medical Monitor.

• Completed prior therapy for CNS metastases (radiation and/or surgery)

• CNS tumor(s) is clinically stable at the time of enrollment

• Patient does not require corticosteroid or antiepileptic therapy for management of CNS metastases

• 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).

Related Conditions & MeSH terms

• Carcinoma
• Cutaneous Melanoma
• Head and Neck Squamous Cell Carcinoma
• Non Small Cell Lung Cancer
• Squamous Cell Carcinoma of Head and Neck
• TNBC - Triple-Negative Breast Cancer
• Triple Negative Breast Neoplasms
• Urothelial Carcinoma

Intervention

Drug:
• RTX-224
RTX-224 monotherapy

Locations

Country	Name	City	State
United States	Virginia Cancer Specialists	Fairfax	Virginia
United States	USC Norris Comprehensive Cancer Center	Los Angeles	California
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	University of California San Francisco Health	San Francisco	California
United States	HonorHealth	Scottsdale	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Rubius Therapeutics

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety Assessment by rate of Adverse Events (AEs)	Measured by incidence of Treatment Emergent Adverse Events (TEAEs)	up to 30 months
Primary	Dose limiting toxicities (DLTs) of RTX-224	As determined by incidence and severity of adverse events	up to 30 months
Secondary	Pharmacodynamics (PD) of RTX-224	As measured by the changes in immune cell populations, e.g., T cells and NK cells	up to 30 months
Secondary	Pharmacokinetics (PK) of RTX-224	Maximum concentration (Cmax) of RTX-224 cells (positive for both 4-1BBL and IL-12 using flow cytometry) in blood after administration will be measured.	up to 30 months
Secondary	Pharmacokinetics (PK) of RTX-224	Time to maximum concentration (tmax) of RTX-224 cells (positive for both 4-1BBL and IL-12 using flow cytometry) in blood after administration will be measured.	up to 30 months
Secondary	Anti-tumor activity of RTX-224	As measured by duration of response (DoR)	up to 30 months
Secondary	Anti-tumor activity of RTX-224	As measured by overall survival (OS)	up to 30 months
Secondary	Anti-tumor activity of RTX-224	As measured by progression free survival (PFS)	up to 30 months
Secondary	Anti-tumor activity of RTX-224	As measured by disease control rate (DCR)	up to 30 months
Secondary	Anti-tumor activity of RTX-224	As measured by objective response rate (ORR)	up to 30 months