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Non-small Cell Lung CancerPhase 1/2NCT06579196

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

A Phase 1/2 study testing Trabedersen and Pembrolizumab in people with Non-small Cell Lung Cancer, run by University of Nebraska at 1 site in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 19 years and older
Conditions the study is for
Non-small Cell Lung Cancer
What is being tested?
Trabedersen and Pembrolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
45 participants
Where
1 siteUnited States
Study dates
12 May 2025to Feb 2029
Phase
Phase 1/2
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 19 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • University of Nebraska Medical Center

    Omaha, Nebraska, 68198

Other trials in United States

About this study

Official title: 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\&#39;s Non-Small Cell Lung Cancer?
Read more

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.
Read the 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.

Being tested
Trabedersen, Pembrolizumab
Keywords
Newly Diagnosed, PD-L1
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • TrabedersenDrug

    Also called OT101

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

  • PembrolizumabDrug

    Also called Keytruda

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

Study groups in NCT06579196
Study groupRoleWhat they receive
Arm I: Dose FindingExperimentalParticipants 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.
Receives: Drug: Trabedersen; Drug: Pembrolizumab
Arm II: TreatmentExperimentalParticipants 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.
Receives: Drug: Trabedersen; Drug: Pembrolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Phase I: Dose Finding

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

    Measured: 18 months

  2. 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

    Measured: 36 months

Secondary outcomes (5)

  1. Best Overall Response

    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,

    Measured: 36 months

  2. Disease Control

    Disease control [CR + PR + stable disease (SD)]

    Measured: 36 months

  3. Duration of Response

    Duration of response (DOR) defined as first response (CR or PR) until disease progression.

    Measured: 36 months

  4. Drug Toxicity

    Toxicity according to Common Terminology Criteria for Adverse Events (CTCAE).

    Measured: 18 months

  5. Overall Survival (OS)

    Overall survival (OS) defined as the time from the first therapy until death.

    Measured: 48 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted30 Aug 2024
  2. Study start12 May 2025
  3. Primary completionMar 2028 (estimated)
  4. Study completionFeb 2029 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Non-randomised
Intervention model
Parallel groups
Model description
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.
Masking
None (open label)
Enrolment
45 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06579196
Sponsor's protocol ID
0740-24-FB
Status last verified
Sep 2026
First submitted
28 Aug 2024
Last updated
25 Sep 2026
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Abughanimeh O, Kaur A, El Osta B, Ganti AK. Novel targeted therapies for advanced non-small lung cancer. Semin Oncol. 2022 Jun;49(3-4):326-336. doi: 10.1053/j.seminoncol.2022.03.003. Epub 2022 Apr 1.

    PubMed 35414419

  • National Comprehensive Cancer Network. Non-small cell lung cancer. Version 2. 2024. Available at: https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf. Accessed Feb 12

  • Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leiby MA, Lubiniecki GM, Shentu Y, Rangwala R, Brahmer JR; KEYNOTE-024 Investigators. Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016 Nov 10;375(19):1823-1833. doi: 10.1056/NEJMoa1606774. Epub 2016 Oct 8.

    PubMed 27718847

  • Mok TSK, Wu YL, Kudaba I, Kowalski DM, Cho BC, Turna HZ, Castro G Jr, Srimuninnimit V, Laktionov KK, Bondarenko I, Kubota K, Lubiniecki GM, Zhang J, Kush D, Lopes G; KEYNOTE-042 Investigators. Pembrolizumab versus chemotherapy for previously untreated, PD-L1-expressing, locally advanced or metastatic non-small-cell lung cancer (KEYNOTE-042): a randomised, open-label, controlled, phase 3 trial. Lancet. 2019 May 4;393(10183):1819-1830. doi: 10.1016/S0140-6736(18)32409-7. Epub 2019 Apr 4.

    PubMed 30955977

  • Herbst RS, Giaccone G, de Marinis F, Reinmuth N, Vergnenegre A, Barrios CH, Morise M, Felip E, Andric Z, Geater S, Ozguroglu M, Zou W, Sandler A, Enquist I, Komatsubara K, Deng Y, Kuriki H, Wen X, McCleland M, Mocci S, Jassem J, Spigel DR. Atezolizumab for First-Line Treatment of PD-L1-Selected Patients with NSCLC. N Engl J Med. 2020 Oct 1;383(14):1328-1339. doi: 10.1056/NEJMoa1917346.

    PubMed 32997907

  • Ozguroglu M, Kilickap S, Sezer A, Gumus M, Bondarenko I, Gogishvili M, Nechaeva M, Schenker M, Cicin I, Ho GF, Kulyaba Y, Zyuhal K, Scheusan RI, Garassino MC, He X, Kaul M, Okoye E, Li Y, Li S, Pouliot JF, Seebach F, Lowy I, Gullo G, Rietschel P. First-line cemiplimab monotherapy and continued cemiplimab beyond progression plus chemotherapy for advanced non-small-cell lung cancer with PD-L1 50% or more (EMPOWER-Lung 1): 35-month follow-up from a mutlicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2023 Sep;24(9):989-1001. doi: 10.1016/S1470-2045(23)00329-7. Epub 2023 Aug 14.

    PubMed 37591293

  • Hellmann MD, Paz-Ares L, Bernabe Caro R, Zurawski B, Kim SW, Carcereny Costa E, Park K, Alexandru A, Lupinacci L, de la Mora Jimenez E, Sakai H, Albert I, Vergnenegre A, Peters S, Syrigos K, Barlesi F, Reck M, Borghaei H, Brahmer JR, O'Byrne KJ, Geese WJ, Bhagavatheeswaran P, Rabindran SK, Kasinathan RS, Nathan FE, Ramalingam SS. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med. 2019 Nov 21;381(21):2020-2031. doi: 10.1056/NEJMoa1910231. Epub 2019 Sep 28.

    PubMed 31562796

  • Jakowlew SB. Transforming growth factor-beta in cancer and metastasis. Cancer Metastasis Rev. 2006 Sep;25(3):435-57. doi: 10.1007/s10555-006-9006-2.

    PubMed 16951986

  • Huber-Ruano I, Raventos C, Cuartas I, Sanchez-Jaro C, Arias A, Parra JL, Wosikowski K, Janicot M, Seoane J. An antisense oligonucleotide targeting TGF-beta2 inhibits lung metastasis and induces CD86 expression in tumor-associated macrophages. Ann Oncol. 2017 Sep 1;28(9):2278-2285. doi: 10.1093/annonc/mdx314.

    PubMed 28911087

  • Bierie B, Moses HL. Tumour microenvironment: TGFbeta: the molecular Jekyll and Hyde of cancer. Nat Rev Cancer. 2006 Jul;6(7):506-20. doi: 10.1038/nrc1926.

    PubMed 16794634

  • Tauriello DVF, Palomo-Ponce S, Stork D, Berenguer-Llergo A, Badia-Ramentol J, Iglesias M, Sevillano M, Ibiza S, Canellas A, Hernando-Momblona X, Byrom D, Matarin JA, Calon A, Rivas EI, Nebreda AR, Riera A, Attolini CS, Batlle E. TGFbeta drives immune evasion in genetically reconstituted colon cancer metastasis. Nature. 2018 Feb 22;554(7693):538-543. doi: 10.1038/nature25492. Epub 2018 Feb 14.

    PubMed 29443964

  • Reck M, Rodriguez-Abreu D, Robinson AG, Hui R, Csoszi T, Fulop A, Gottfried M, Peled N, Tafreshi A, Cuffe S, O'Brien M, Rao S, Hotta K, Leal TA, Riess JW, Jensen E, Zhao B, Pietanza MC, Brahmer JR. Five-Year Outcomes With Pembrolizumab Versus Chemotherapy for Metastatic Non-Small-Cell Lung Cancer With PD-L1 Tumor Proportion Score >/= 50. J Clin Oncol. 2021 Jul 20;39(21):2339-2349. doi: 10.1200/JCO.21.00174. Epub 2021 Apr 19.

    PubMed 33872070

  • Uckun FM, Qazi S, Trieu VN. Proof of concept for the clinical utility of a convection enhanced delivery platform for immune-oncology drugs against brain tumors. Cancer Rep Rev. 2020;3:1-8

  • Jaschinski F, Korhonen H, Janicot M. Design and Selection of Antisense Oligonucleotides Targeting Transforming Growth Factor Beta (TGF-beta) Isoform mRNAs for the Treatment of Solid Tumors. Methods Mol Biol. 2015;1317:137-51. doi: 10.1007/978-1-4939-2727-2_9.

    PubMed 26072406

  • Jaschinski F, Rothhammer T, Jachimczak P, Seitz C, Schneider A, Schlingensiepen KH. The antisense oligonucleotide trabedersen (AP 12009) for the targeted inhibition of TGF-beta2. Curr Pharm Biotechnol. 2011 Dec;12(12):2203-13. doi: 10.2174/138920111798808266.

    PubMed 21619536

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Trabedersen and Pembrolizumab in people with Non-small Cell Lung Cancer, run by University of Nebraska at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 16 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: under way, not looking for participants, as of the sponsor's last update on 25 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: Dose Finding (time frame: 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT06579196, which also lists 31 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Sep 2026; AzTrials last refreshed its copy on 7 Nov 2026.

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