OT-101 (Trabedersen) plus pembrolizumab for newly diagnosed advanced non-small cell lung cancer with PD-L1 positivity
Evaluation of Trabedersen (OT-101) With Pembrolizumab in Patients With Newly Diagnosed Advanced Non-Small Cell Lung Cancer and Positive PD-L1
This trial will test whether adding OT-101 (Trabedersen) to pembrolizumab helps adults with newly diagnosed advanced non-small cell lung cancer whose tumors have PD-L1 ≥1%.
Quick facts
| Phase | Phase1; Phase2 |
|---|---|
| Study type | Interventional |
| Enrollment | 45 (estimated) |
| Ages | 19 Years and up |
| Sex | All |
| Sponsor | University of Nebraska Academic / other |
| Drugs / interventions | pembrolizumab, immunotherapy, radiation, prednisone |
| Locations | 1 site (Omaha, Nebraska) |
| Trial ID | NCT06579196 on ClinicalTrials.gov |
What this trial studies
This is a Phase 1/2 interventional trial combining the antisense oligonucleotide OT-101 (Trabedersen) with the PD-1 inhibitor pembrolizumab in adults with metastatic or unresectable NSCLC and PD-L1 ≥1%. Phase 1 uses a BOIN dose escalation/de-escalation design to identify dose-limiting toxicities and the recommended Phase 2 dose of OT-101 given with standard pembrolizumab. OT-101 is given intravenously for 4 days every 2 weeks while pembrolizumab is given intravenously every 6 weeks. In Phase 2 subjects receive the recommended dose of OT-101 with pembrolizumab until disease progression by iRECIST, relapse, or death, with safety and efficacy outcomes monitored throughout.
Who should consider this trial
Good fit: Adults (≥19 years) with histologically proven metastatic or unresectable NSCLC, PD-L1 ≥1%, measurable disease, ECOG ≤2, adequate organ function, and no prior systemic therapy for metastatic disease are the intended candidates.
Not a fit: Patients with PD-L1 <1%, prior immunotherapy for metastatic NSCLC, poor organ function, or other contraindications to study drugs are unlikely to benefit from participation.
Why it matters
Potential benefit: If successful, the combination could improve tumor control and clinical outcomes compared with current pembrolizumab-alone approaches for PD-L1–positive advanced NSCLC.
How similar studies have performed: Combining TGF-β–targeting agents with PD-1/PD-L1 blockade is a biologically plausible but still early and relatively unproven approach in NSCLC, with limited positive signals in early-phase studies so far.
Eligibility criteria
Show full inclusion / exclusion criteria
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
Where this trial is running
Omaha, Nebraska
- University of Nebraska Medical Center — Omaha, Nebraska, United States (Recruiting)
Study contacts
- Principal investigator: Omar Abughanimeh, MBBS — University of Nebraska
- Study coordinator: Samuel P Anderson, BS
- Email: samuanderson@unmc.edu
- Phone: 402-559-1250
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.