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

NCT06579196 | Recruiting Phase 1 DMC FDA Drug

• 1 other identifier: 0740-24-FB
• Study Type: interventional
• Target: 45
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Non-small Cell Lung Cancer

Keywords

Newly Diagnosed; PD-L1

Outcome Measures

Primary Outcomes (2)

• Phase I: Dose Finding

  Dose Limiting toxicity (DLT) and Maximum Tolerated Dose (MTD)

  18 months

• Phase II: Progression-Free Survival (PFS)

  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 Outcomes (5)

• Best Overall Response

  36 months

• Disease Control

  36 months

• Duration of Response

  36 months

• Drug Toxicity

  18 months

• Overall Survival (OS)

  48 months

Study Arms (2)

Arm I: Dose Finding

EXPERIMENTAL

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; Drug: Pembrolizumab

Arm II: Treatment

EXPERIMENTAL

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; Drug: Pembrolizumab

Interventions

Trabedersen DRUG

Trabedersen (OT-101) is a synthetic antisense oligodeoxynucleotide that specifically inhibits the production of Transforming growth factor-beta 2 (TGF-β2).

Also known as: OT101

Arm I: Dose Finding; Arm II: Treatment

Pembrolizumab DRUG

Pembrolizumab is a humanized anti-programmed death (PD-1) monoclonal antibody.

Also known as: Keytruda

Arm I: Dose Finding; Arm II: Treatment

Eligibility Criteria

• Age: 19 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Nebraska: lead

Study Sites (1)

University of Nebraska Medical Center

Omaha, Nebraska, 68198, United States

RECRUITING

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Related Links

• Pharmacokinetic-Pharmacodynamic (PKPD) Analysis For P001 - Phase 1/2 Clinical Trial For OT-101 Against Pancreatic Cancer, Melanoma, and Colorectal Cancer
• Mechanism of Action for OT-101 TGF-β Immunotherapy

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

Trabedersen; pembrolizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Study Officials

• Omar Abughanimeh, MBBS

  University of Nebraska

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Samuel P Anderson, BS

CONTACT

402-559-1250; samuanderson@unmc.edu

Taylor A Johnson, MA

CONTACT

402-559-4596; taylora.johnson@unmc.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are enrolled into the Phase I arm until the recommended phase 2 dose (RP2D) is determined. Participants who receive the RP2D in Phase I are reassigned to the Phase II arm.

Study Record Dates

• First Submitted: August 28, 2024
• First Posted: August 30, 2024
• Study Start: May 12, 2025
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): February 1, 2029
• Last Updated: July 24, 2025

Record last verified: 2025-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)