RTX-224 Monotherapy in Patients With Solid Tumors

• ClinicalTrials.gov Identifier: NCT05219578
• Recruitment Status: Terminated
• First Posted: February 2, 2022
• Last Update Posted: December 9, 2022
• Sponsor: Rubius Therapeutics
• Information provided by (Responsible Party): Rubius Therapeutics

Tracking Information

• First Submitted Date: January 6, 2022
• First Posted Date: February 2, 2022
• Last Update Posted Date: December 9, 2022
• Actual Study Start Date: January 12, 2022
• Actual Primary Completion Date: November 30, 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 28, 2022)

• Safety Assessment by rate of Adverse Events (AEs) [ Time Frame: up to 30 months ]
  Measured by incidence of Treatment Emergent Adverse Events (TEAEs)
• Dose limiting toxicities (DLTs) of RTX-224 [ Time Frame: up to 30 months ]
  As determined by incidence and severity of adverse events

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: February 24, 2022)

• Pharmacodynamics (PD) of RTX-224 [ Time Frame: up to 30 months ]
  As measured by the changes in immune cell populations, e.g., T cells and NK cells
• Pharmacokinetics (PK) of RTX-224 [ Time Frame: up to 30 months ]
  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.
• Pharmacokinetics (PK) of RTX-224 [ Time Frame: up to 30 months ]
  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.
• Anti-tumor activity of RTX-224 [ Time Frame: up to 30 months ]
  As measured by duration of response (DoR)
• Anti-tumor activity of RTX-224 [ Time Frame: up to 30 months ]
  As measured by overall survival (OS)
• Anti-tumor activity of RTX-224 [ Time Frame: up to 30 months ]
  As measured by progression free survival (PFS)
• Anti-tumor activity of RTX-224 [ Time Frame: up to 30 months ]
  As measured by disease control rate (DCR)
• Anti-tumor activity of RTX-224 [ Time Frame: up to 30 months ]
  As measured by objective response rate (ORR)

Original Secondary Outcome Measures (submitted: January 28, 2022)

• Pharmacodynamics (PD) of RTX-224 [ Time Frame: up to 30 months ]
  As measured by the changes in immune cell populations, e.g., T cells and NK cells
• Pharmacokinetics (PK) of RTX-224 [ Time Frame: up to 30 months ]
  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.
• Pharmacokinetics (PK) of RTX-224 [ Time Frame: up to 30 months ]
  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.
• Anti-tumor activity of RTX-224 [ Time Frame: up to 30 months ]
  As measured by duration of response (DoR)
• Anti-tumor activity of RTX-224 [ Time Frame: up to 30 months ]
  As measured by overall survival (OS)
• Anti-tumor activity of RTX-224 [ Time Frame: up to 30 months ]
  As measured by progression free survival (PFS)
• Anti-tumor activity of RTX-224 [ Time Frame: up to 30 months ]
  As measured by disease control rate (DCR)

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: RTX-224 Monotherapy in Patients With Solid Tumors
• Official Title: A Phase 1/2 Study of RTX-224 for the Treatment of Patients With Advanced Solid Tumors
• Brief 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.
• Detailed 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.
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Non-Randomized; Intervention Model: Sequential Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

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

Intervention

Drug: RTX-224

RTX-224 monotherapy

Study Arms

• Experimental: RTX-224 Dose Escalation
  Phase 1: RTX-224 monotherapy dose escalation in Solid Tumors, administered intravenously on Day 1 of each cycle.
  Intervention: Drug: RTX-224
• Experimental: RTX-224 Dose Expansion
  Phase 2: RTX-224 monotherapy dose expansion in Solid Tumors, administered intravenously on Day 1 of each cycle.
  Intervention: Drug: RTX-224

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Terminated
• Actual Enrollment (submitted: December 7, 2022): 7
• Original Estimated Enrollment (submitted: January 28, 2022): 128
• Actual Study Completion Date: November 30, 2022
• Actual Primary Completion Date: November 30, 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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).

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT05219578
• Other Study ID Numbers: RTX-224-01
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Rubius Therapeutics
• Original Responsible Party: Same as current
• Current Study Sponsor: Rubius Therapeutics
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Rubius Therapeutics
• Verification Date: December 2022