Recruiting

Phase 1

Phase 2

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

Sponsor:

University of Nebraska

Code:

NCT06579196

Conditions

Non-small Cell Lung Cancer

Eligibility Criteria

Sex: All

Age: 19+

Healthy Volunteers: Not accepted

Interventions

Trabedersen

Pembrolizumab

Study Details

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

Study ID

NCT06579196

Start date

May 12, 2025

Status verified date

Apr, 2025

Completion date

Feb, 2029

Anticipated

Primary completion date

Mar, 2028

Anticipated

Eligibility Criteria

Sex: All

Age: 19+

Healthy Volunteers: Not accepted

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 Design

Enrollment

45 participants

Anticipated

Allocation

Non randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

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.

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.

Interventions

Trabedersen

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

Pembrolizumab

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

Primary outcome measure

Phase I: Dose Finding [ Time Frame: 18 months ]
Phase II: Progression-Free Survival (PFS) [ Time Frame: 36 months ]

Central Contacts and Locations

Central contacts

Samuel P Anderson, BS

402-559-1250 samuanderson@unmc.edu

Taylor A Johnson, MA

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

Locations

University of Nebraska Medical Center

Recruiting

Omaha, Nebraska, United States, 68198

Contacts

Omar Abughanimeh, MBBS

402-559-7511 omar.abughanimeh@unmc.edu

Principal Investigator:

Omar Abughanimeh, MBBS

More Information

Sponsor

University of Nebraska

Last update posted

Jul 24, 2025

Last verified

Apr, 2025

Keywords

Newly Diagnosed
PD-L1

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Nebraska on 2025-07-24.