Can blocking TGF-Beta 2 boost immunotherapy in lung cancer?
NCT ID NCT06579196
First seen Sep 25, 2026 · Last updated Sep 25, 2026
Summary
Researchers are testing whether adding an experimental drug called trabedersen (OT-101) to standard pembrolizumab helps adults with newly diagnosed advanced non-small cell lung cancer. Trabedersen blocks a protein called TGF-beta 2, which may help the immune system fight the cancer. Participants receive trabedersen by IV for four days every two weeks and pembrolizumab by IV every six weeks. The trial measures side effects, finds the best dose, and tracks how long participants live without their cancer getting worse.
What this could mean
Our plain-language read of the trial. This is informational only, not medical advice or a prediction.
- Active substance
- trabedersen (OT-101), an experimental drug that blocks TGF-beta 2, given with pembrolizumab
- What this could lead to
- If the combination works, it could offer a new way to treat advanced non-small cell lung cancer that has not yet received treatment.
- What could go wrong
- This is an early-phase trial with about 45 participants, so safety and dosing are still being worked out. The combination may not slow the cancer, and adding trabedersen could cause side effects.
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Study facts
What this study's own registry entry says, in plain language.
- Phase
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Phase 1/2
Runs two stages together: safety and dose first, then whether the treatment works.
- Participants
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About 45 people
The number the study aims to enrol. It can still change while the study runs.
- Started
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May 2025
- Expected to finish
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Feb 2029
An estimate. End dates often move.
- Lead sponsor
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Other sponsor
The registry's catch-all category, for sponsors it does not file as a company, a government agency, or a research network.
Who can take part
This study's own entry requirements. Only the study team can say for certain whether you qualify.
- Ages
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19 years and older
- Sex
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Anyone
- Healthy volunteers
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Not accepted
This study is not open to healthy volunteers. The entry requirements below say who it is open to.
Show the full entry requirements Hide the full entry requirements
Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.
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
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Conditions
The condition(s) this trial relates to.
As listed by the trial registrant
The condition terms exactly as the trial's registrant entered them.
Contacts and locations
Locations
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University of Nebraska Medical Center
Omaha, Nebraska, 68198, United States
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