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

July 23, 2025 updated by: University of Nebraska

Evaluation of Trabedersen (OT-101) With Pembrolizumab in Patients With Newly Diagnosed Advanced Non-Small Cell Lung Cancer and Positive PD-L1

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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed 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.

Study Type

Interventional

Enrollment (Estimated)

45

Phase

  • 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 Contact

Study Contact Backup

Study Locations

  • United States
    • Nebraska
      • Omaha, Nebraska, United States, 68198
        • Recruiting
        • University of Nebraska Medical Center
        • Contact:
        • Principal Investigator:
          • Omar Abughanimeh, MBBS

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

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Age ≥ 19 years
  • 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
  • No 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
  • 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 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:

  • Received any systemic treatments including investigational agents within the last 28 days
  • Known hypersensitivity to any of the excipients of OT101 or pembrolizumab
  • 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 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
  • 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

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
Intervention / Treatment
Experimental: Arm I: Dose Finding

Participants receive either 140, 190, or 250 mg/m2 intravenous OT-101/Trabedersen for up to 12 weeks using a 4 days on 10 days off dosing schedule. The dose level is determined according to the Bayesian optimal interval (BOIN) design with cohort size 3.

Participants receive concurrent administration of 400 mg intravenous Pembrolizumab every 6 weeks.
Drug: Trabedersen
Trabedersen (OT-101) is a synthetic antisense oligodeoxynucleotide that specifically inhibits the production of Transforming growth factor-beta 2 (TGF-β2).
Other Names:
  • OT101
Drug: Pembrolizumab
Pembrolizumab is a humanized anti-programmed death (PD-1) monoclonal antibody.
Other Names:
  • Keytruda
Experimental: Arm II: Treatment

Participants receive the recommended phase II dose of intravenous OT-101/Trabedersen (140, 190, or 250 mg/m2) until progression using a 4 days on 10 days off dosing schedule.

Participants receive concurrent administration of 400 mg intravenous Pembrolizumab every 6 weeks.
Drug: Trabedersen
Trabedersen (OT-101) is a synthetic antisense oligodeoxynucleotide that specifically inhibits the production of Transforming growth factor-beta 2 (TGF-β2).
Other Names:
  • OT101
Drug: Pembrolizumab
Pembrolizumab is a humanized anti-programmed death (PD-1) monoclonal antibody.
Other Names:
  • Keytruda

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Phase I: Dose Finding
Time Frame: 18 months
Dose Limiting toxicity (DLT) and Maximum Tolerated Dose (MTD)
18 months
Phase II: Progression-Free Survival (PFS)
Time Frame: 36 months
Progression-Free Survival (PFS) defined as first therapy until the first documentation of clinical progression, relapse, or death due to any cause. Participants not experiencing an event of interest will be right-censored at last known disease status
36 months

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Best Overall Response
Time Frame: 36 months
Best overall response, defined as the best overall response observed during the evaluation period (up to 12 weeks of treatment): CR, PR, SD, or PD,
36 months
Disease Control
Time Frame: 36 months
Disease control [CR + PR + stable disease (SD)]
36 months
Duration of Response
Time Frame: 36 months
Duration of response (DOR) defined as first response (CR or PR) until disease progression.
36 months
Drug Toxicity
Time Frame: 18 months
Toxicity according to Common Terminology Criteria for Adverse Events (CTCAE).
18 months
Overall Survival (OS)
Time Frame: 48 months
Overall survival (OS) defined as the time from the first therapy until death.
48 months

Collaborators and Investigators

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

Sponsor

University of Nebraska

Investigators

  • Principal Investigator: Omar Abughanimeh, MBBS, University of Nebraska

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

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)

May 12, 2025

Primary Completion (Estimated)

March 1, 2028

Study Completion (Estimated)

February 1, 2029

Study Registration Dates

First Submitted

August 28, 2024

First Submitted That Met QC Criteria

August 28, 2024

First Posted (Actual)

August 30, 2024

Study Record Updates

Last Update Posted (Actual)

July 24, 2025

Last Update Submitted That Met QC Criteria

July 23, 2025

Last Verified

April 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0740-24-FB

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

product manufactured in and exported from the U.S.

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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