First-line Treatment With Dacomitinib Plus Anlotinib for Patients With Advanced NSCLC With EGFR 21L858R Mutations

Официальное название

An Open Label, Multicenter, Phase I/IIB Study of Dacomitinib Plus Anlotinib for Advanced Non-Small Cell Lung Cancer (NSCLC) Harboring Epidermal Growth Factor Receptor (EGFR) 21-L858R Mutations.

Обзор

This is a multicenter, open label, Phase I/IIB study investigating the efficacy and safety of treatment with dacomitinib plus anlotinib as first-line therapy for patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) 21-L858R mutations. This study comprises two parts: 1. A dose escalation Phase I study to determine the recommended phase II dose. 2. a multi-center, open label, randomized controlled, Phase IIB study.

Вмешательства

• Препарат Dacomitinib+Anlotinib
  The dose of each drug in the combination Decomitinib and Anlotinib will be escalated or de-escalated until the recommended phase II dose (RP2D) is reached. Patients will then be treated with RP2D orally once a day.
• Препарат Dacomitinib
  Dacomitinib orally on a continuous daily basis at a starting dose of 45 mg once a day until progressive disease.

Первичные конечные точки

• Overall safety profile [Срок оценки: Day 21 of Cycle 1, every 6 weeks until disease progression or death due to any cause, whichever occurred first (up to 22 months)]
• Progression Free Survival (PFS) [Срок оценки: Day 21 of Cycle 1, every 6 weeks until disease progression or death due to any cause, whichever occurred first (up to 22 months)]

Вторичные конечные точки (2)

• Overall Survival (OS) [Срок оценки: 48 months]
• Best Overall Response (BOR) [Срок оценки: From baseline until disease progression, up to 48 months]

Критерии участия

Критерии включения

• ≥18 years of age and ≤75 years;
• Provision of a voluntarily given, personally signed and dated, written informed consent document;
• Histologically documented, unresectable, inoperable, locally advanced, recurrent or metastatic stage IIIB or IV non-small cell lung cancer (NSCLC);
• It is acceptable for subjects with the presence of EGFR activating mutation (exon 19 deletion and the L858R mutation in exon 21) to be included in this Phase I study; Only subjects with the L858R mutation in exon 21 to be included in this Phase IIb;
• At least one measurable disease by RECIST criteria version 1.1;
• Patients with controlled or stable brain metastases;
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1, and life expectancy of at least 3 months;
• No prior treatment with systemic therapy for advanced NSCLC, including TCM treatments;
• Able to comply with required protocol procedures and able to receive oral medications;
• Adequate organ function, including:

(1) Adequate bone marrow function Hemoglobin≥90g/L, absolute neutrophil count (ANC) should be ≥ 1.5x109/L, platelets should be ≥ 80x109/L; (2) Adequate liver function Total bilirubin ≤ 1.5 x upper normal limit (ULN), Aspartate Aminotransferase (AST) (SGOT) ≤ 2.5 x ULN (≤ 5.0 x ULN if hepatic metastases), Alanine Aminotransferase (ALT) (SGPT) ≤ 2.5 x ULN (≤ 5.0 x ULN if hepatic metastases), Creatinine≤ 1.5 x upper normal limit (ULN), or ≥ 60 mL/min; (3) Cardiac function: LVEF≥50% assessed by Doppler ultrasound；

Критерии исключения

• Small cell lung cancer (including mixed small cell and non-small cell lung cancer) and squamous cell carcinoma with cavitation;
• Patients with concurrent EGFR T790M mutation or unknown mutation status or other mutation types;
• Diagnosis of any other malignancy during the last 5 years, or with other malignancies at present;
• Patients with pre-existing meningeal metastases;
• Patients who have concurrent other malignant tumors;
• Any history of hemoptysis, hematochezia, bloody sputum;
• Tumor invasion or adjacent major vessels;
• Patients with uncontrolled or significant systematic disease, including: active infection, thyroid dysfunction, uncontrolled hypertension, unstable angina pectoris, congestive heart failure, or myocardial infarction within 6 months, or severe arrhythmia requiring medication;
• A history of other diseases, or metabolic dysfunction, or physical examination or laboratory results suggestive of a disease or condition that precludes the use of an investigational drug, or may affect the interpretation of the study results, or expose the patient to a high risk of treatment complications;
• Any astrointestinal disorders resulting in inability to take medications orally, or requiring intravenous (IV) nutrition, or previous surgery impair drug absorption;
• Pregnant or lactating females;
• Patients allergic to any pharmaceutical ingredient.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Shanghai Chest Hospital — Шанхай

Публикации

• Wu YL, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Tsuji F, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Nadanaciva S, Sandin R, Mok TS. Dacomitinib versus gefitinib as first-line treatment for patients with EGFR-mutation-positive non-small-cell lung cancer (ARCHER 1050): a randomised, open-label, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1454-1466. doi: PMID 28958502
• Mok TS, Cheng Y, Zhou X, Lee KH, Nakagawa K, Niho S, Lee M, Linke R, Rosell R, Corral J, Migliorino MR, Pluzanski A, Sbar EI, Wang T, White JL, Wu YL. Improvement in Overall Survival in a Randomized Study That Compared Dacomitinib With Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer and EGFR-Activating Mutations. J Clin Oncol. 2018 Aug 1;36(22):2244-2250. doi: 10.1200/JCO.2018.78.79 PMID 29864379
• Cheng Y, Mok TS, Zhou X, Lu S, Zhou Q, Zhou J, Du Y, Yu P, Liu X, Hu C, Lu Y, Zhang Y, Lee KH, Nakagawa K, Linke R, Wong CH, Tang Y, Zhu F, Wilner KD, Wu YL. Safety and efficacy of first-line dacomitinib in Asian patients with EGFR mutation-positive non-small cell lung cancer: Results from a randomized, open-label, phase 3 trial (ARCHER 1050). Lung Cancer. 2021 Apr;154:176-185. doi: 10.1016/j.lung PMID 33721611
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• Perdrizet K, Leighl NB. The Role of Angiogenesis Inhibitors in the Era of Immune Checkpoint Inhibitors and Targeted Therapy in Metastatic Non-Small Cell Lung Cancer. Curr Treat Options Oncol. 2019 Feb 18;20(3):21. doi: 10.1007/s11864-019-0617-6. PMID 30778772
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• Saito H, Fukuhara T, Furuya N, Watanabe K, Sugawara S, Iwasawa S, Tsunezuka Y, Yamaguchi O, Okada M, Yoshimori K, Nakachi I, Gemma A, Azuma K, Kurimoto F, Tsubata Y, Fujita Y, Nagashima H, Asai G, Watanabe S, Miyazaki M, Hagiwara K, Nukiwa T, Morita S, Kobayashi K, Maemondo M. Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-squamous non-small-cell lung PMID 30975627
• Zhou Q, Xu CR, Cheng Y, Liu YP, Chen GY, Cui JW, Yang N, Song Y, Li XL, Lu S, Zhou JY, Ma ZY, Yu SY, Huang C, Shu YQ, Wang Z, Yang JJ, Tu HY, Zhong WZ, Wu YL. Bevacizumab plus erlotinib in Chinese patients with untreated, EGFR-mutated, advanced NSCLC (ARTEMIS-CTONG1509): A multicenter phase 3 study. Cancer Cell. 2021 Sep 13;39(9):1279-1291.e3. doi: 10.1016/j.ccell.2021.07.005. Epub 2021 Aug 12. PMID 34388377

Идентификаторы

NCT: NCT05271916 · IS22001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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