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

Официальное название

Evaluation of Trabedersen (OT-101) With Pembrolizumab in Patients With Newly Diagnosed Advanced Non-Small Cell Lung Cancer and Positive PD-L1

Обзор

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.

Подробное описание

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.

Вмешательства

• Препарат Trabedersen
  Trabedersen (OT-101) is a synthetic antisense oligodeoxynucleotide that specifically inhibits the production of Transforming growth factor-beta 2 (TGF-β2).
• Препарат Pembrolizumab
  Pembrolizumab is a humanized anti-programmed death (PD-1) monoclonal antibody.

Первичные конечные точки

• Phase I: Dose Finding [Срок оценки: 18 months]
• Phase II: Progression-Free Survival (PFS) [Срок оценки: 36 months]

Вторичные конечные точки (5)

• Best Overall Response [Срок оценки: 36 months]
• Disease Control [Срок оценки: 36 months]
• Duration of Response [Срок оценки: 36 months]
• Drug Toxicity [Срок оценки: 18 months]
• Overall Survival (OS) [Срок оценки: 48 months]

Критерии участия

Критерии включения

• 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

Критерии исключения

• 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

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Нерандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• University of Nebraska Medical Center — Omaha

Публикации

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• 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
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• 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. Lan PMID 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. PMID 32997907
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• 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 PMID 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. PMID 16951986

Идентификаторы

NCT: NCT06579196 · 0740-24-FB

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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