Trabedersen (OT-101) With Pembrolizumab for Newly Diagnosed Advanced NSCLC and Positive PD-L1

Sponsor: University of Nebraska

Sponsor score: 40

ClinicalTrials ID:NCT06579196

This trial evaluates the safety, dosage, and efficacy of OT-101 with Pembrolizumab in advanced NSCLC with PD-L1 ≥1%. Participants receive OT-101 biweekly and Pembrolizumab every 6 weeks. Eligibility includes age ≥19, ECOG ≤2, and adequate organ function. Trabedersen targets TGF-β2, while Pembrolizumab is an anti-PD-1 antibody.

Patient Parameters

Program Overview

The goal of this clinical trial is to: 1) evaluate the safety and recommended dose of the drug OT-101/Trabedersen when combined with Pembrolizumab and 2) determine the efficacy of the combination therapy in adults with certain types of Non-Small Cell Lung Cancer. The main question(s) it aims to answer are:

  • What medical problems to participants have when taking OT101 together with Pembrolizumab?
  • What is the correct dose of OT-101 to use when evaluating the safety and efficacy of the combination therapy?
  • Does the combination therapy delay progression or relapse of the participant's Non-Small Cell Lung Cancer?

Participants will:

  • Receive intravenous OT-101/Trabedersen for 4 days once every 2 weeks. Clinic visits are required to receive and disconnect the infusion.
  • Receive intravenous Pembrolizumab once every 6 weeks.

Description

The goal of this clinical trial is to: 1) evaluate the safety and recommended dose of the drug OT-101/Trabedersen when combined with Pembrolizumab and 2) determine the efficacy of the combination therapy in adults with certain types of Non-Small Cell Lung Cancer. The main question(s) it aims to answer are:

  • What medical problems to participants have when taking OT101 together with Pembrolizumab?
  • What is the correct dose of OT-101 to use when evaluating the safety and efficacy of the combination therapy?
  • Does the combination therapy delay progression or relapse of the participants Non-Small Cell Lung Cancer?

Participants will:

  • Receive intravenous OT-101/Trabedersen for 4 days once every 2 weeks. Clinic visits are required to receive and disconnect the infusion.
  • Receive intravenous Pembrolizumab once every 6 weeks.

In Phase I, dose escalation/de-escalation of OT101/Trabedersen is performed using a BOIN design to determine dose limiting toxicity (DLT) and the recommended phase 2 dose (RP2D) when combined with Pembrolizumab.

In Phase II, subjects receive the RP2D of OT101/Trabedersen together with Pembrolizumab until disease relapse, progression [as determined by immune Response Evaluation Criteria in Solid Tumours (iRECIST) criteria], or death.

Eligibility Criteria

Inclusion Criteria

  • Age ≥ 19 years

  • A histologically/cytologically proven diagnosis of non-small cell lung cancer (NSCLC) with a PD-L1 of at least 1%

  • Metastatic disease or disease not amenable for curative intent therapy

  • Have not received any prior treatment for metastatic NSCLC. Early-stage disease therapy acceptable if completed at least six months prior and did not include immunotherapy.

  • Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2

  • Must have measurable disease by RECIST criteria

  • Adequate organ and marrow function as defined below:

    • Absolute neutrophil count ≥1,500/mm3
    • Platelets ≥100,000/mm3
    • Hemoglobin >9.0 mg/dL
    • Creatinine clearance > 60 ml/min/1.73 m2 using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula
    • Total serum bilirubin <1.5 X upper limit of normal (ULN) except if known to have Gilbert's syndrome, then excluded if total bilirubin >2.5 X ULN
    • Aspartate aminotransferase (AST)/serum glutamic-oxaloacetic transaminase (SGOT) and alanine aminotransferase (ALT)/serum glutamic-pyruvic transaminase (SGPT) ≤ 2.5 x ULN; if participant has liver metastases, ≤5x ULN

  • For females of childbearing potential, negative serum or urine pregnancy test ≤7 days of treatment, & agree to use effective contraceptive during the treatment & 90 days after end of treatment

  • Male participants must agree to use effective contraception during the trial & for 90 days after end of treatment

  • Able to give informed consent

Exclusion Criteria

  • Has received any systemic treatments including investigational agents within the last 28 days
  • Known hypersensitivity to any of the excipients of OT101 or pembrolizumab
  • Has received radiotherapy within 14 days of the study intervention. Palliative radiation is allowed during the study with a 1-week washout
  • Pregnant or breast-feeding women
  • History of autoimmune diseases that has required systemic treatment in the past 2 years with agents such as but not limited to corticosteroids or immunosuppressive drugs. Thyroid replacement for hypothyroidism, insulin treatment for type I diabetes or corticosteroids adrenal/pituitary insufficiency are allowed.
  • Uncontrolled systemic diseases that in the opinion of the investigator may interfere with the protocol activities
  • Known active second malignancy that needs treatment. Exceptions include basal cell or squamous cancers of the skin, bladder or cervical carcinoma in situ, prostate cancer on hormone therapy alone.
  • Immunodeficiency diagnosis or receiving chronic steroids that exceed a dose equivalent to prednisone 10 mg daily
  • Has symptomatic brain metastases. Asymptomatic metastases or having received treatment for brain metastases and are off steroid therapy is acceptable.
  • Known psychiatric or substance use that would interfere with the study requirements
  • Inability to co-operate with the requirements of the protocol

Locations

FACILITYZIPCITYSTATE
University of Nebraska Medical Center68198OmahaNebraska

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