Anlotinib Hydrochloride Capsules Combined With TQB2450 in the Treatment of Endometrial Cancer

Официальное название

Efficacy of Anlotinib Hydrochloride Capsules Combined With TQB2450 in the Treatment of Endometrial Cancer in a Randomized, Controlled, Open-label, Multicenter Phase III Clinical Trial

Обзор

To demonstrate that anlotinib hydrochloride capsules combined with TQB2450 injection can significantly prolong progression-free survival (PFS) compared with chemotherapy in patients with recurrent or metastatic endometrial cancer that is non- microsatellite instability high (non-MSI-H) or DNA mismatch repair deficient (non-dMMR).

Вмешательства

• Препарат Anlotinib hydrochloride capsule + TQB2450 injection
  Anlotinib hydrochloride capsule is a multi-target tyrosine kinase inhibitor, which targets VEGFR (VEGFR-1, VEGFR-2 and VEGFR-3), PDGFR, FGFR and c-Kit, etc. It can inhibit tumor progression by inhibiting angiogenesis and tumor growth at the same time. TQB2450 injection is a humanized monoclonal antibody targeting programmed death ligand 1 (PD-L1) that prevents the binding of PD-L1 to the PD-1 and B7.1 receptors on the T-cell surface, allowing T-cell reactivation and thus enhancing the immune re
• Препарат Chemotherapy drug
  Based on each patient's condition and previous treatment history, the investigator will select one of the chemotherapy drugs (including Paclitaxel, Albumin, Doxorubicin and Doxorubicin hydrochloride) for treatment.

Первичные конечные точки

• Progression-free survival (PFS) assessed by independent imaging review committee (IRC) [Срок оценки: Up to 36 months after study start]

Вторичные конечные точки (12)

• Overall survival (OS) [Срок оценки: Up to 36 months after study start]
• Progression-free survival (PFS) assessed by investigators [Срок оценки: Up to 36 months after study start]
• Objective mitigation rate (ORR) [Срок оценки: Up to 36 months after study start]
• Duration of Response (DOR) [Срок оценки: Up to 36 months after study start]
• Disease control rate (DCR) [Срок оценки: Up to 36 months after study start]
• Incidence and severity of abnormal laboratory values [Срок оценки: Up to 36 months after study start]
• Incidence and severity of adverse event rate Adverse events (AE), serious adverse event (SAE) [Срок оценки: Up to 36 months after study start]
• Incidence of dose interruptions, dose reductions, and dose discontinuations due to study-drug-related toxicity during the trial [Срок оценки: Up to 36 months after study start]
• Immunogenicity of TQB2450 [Срок оценки: Before administration (-15 minutes) in cycles 1, 2, 5, and 9, and 90 days after the last dose (±7days), each cycle is 21 days]
• European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) [Срок оценки: Up to 96 weeks]
• European Quality of Life 5 Dimensions 5 Level Version (EQ-5D-5L) [Срок оценки: Up to 96 weeks]
• European Organization for Research on Treatment of Cancer Endometrial cancer Specific scale QLQ-EN24 [Срок оценки: Up to 96 weeks]

Критерии участия

Критерии включения

• Recurrent or metastatic advanced endometrial cancer confirmed by histopathology;
• Patients failed to respond to 1-2 lines of platinum-based doublet-based therapy;
• Provide a traceable MMR/MSI status report or provide biological samples for DNA mismatch repair/microsatellite instability (MMR/MSI) status testing with non-MSI-high (non-MSI-H) or non-dMMR；
• Patients who cannot undergo radical surgery/radiotherapy;
• Age: ≥18 years old (when signing the informed consent); Eastern Cooperative Oncology Group (ECOG) performance status (PS) score: 0-1; The expected survival time is more than 3 months；
• At least one measurable lesion (RECIST 1.1);
• Good function of the major organs；
• Women of childbearing age should agree that they must use a contraceptive method (e.g. Intra-uterine device (IUD), contraceptive pill, or condom) during the study and for 6 months after the study; A negative serum pregnancy test within 7 days before study entry and must be non-lactating；
• Subjects voluntarily joined this study, signed informed consent, and had good compliance；

Критерии исключения

• Previous use of bevacizumab, endostar, anlotinib, apatinib, lenvatinib, sorafenib, sunitinib, regorafenib, fruquintinib and other anti-angiogenic drugs or immunotherapy drugs targeting programmed cell death protein 1 (PD-1), PD-L1 and other related cells；
• Patients received anti-tumor indications of Chinese patent medicine approved by National Medical Products Administration (NMPA) within 2 weeks before the study treatment；
• Pathology suggested carcinosarcoma (malignant mullerian mixed tumor), endometrial leiomyosarcoma or other high-grade sarcoma, or endometrial stromal sarcoma；
• Hormone therapy for endometrial cancer had been received within 1 week before the first dose of trial medication；
• Surgery, chemotherapy, radiation therapy, or other anticancer therapy had been received within 4 weeks before the initiation of study treatment (the washout period was calculated from the end of the last treatment). The half-life of oral targeted drugs was less than 5 drugs；
• Subjects with known central nervous system metastases and/or carcinomatous meningitis; The patients were not asymptomatic or were treated and stable, had no radiographic evidence of new or expanding brain metastases for at least 2 weeks after treatment for brain metastases, and had discontinued steroids or anticonvulsant therapy for at least 14 days before the initiation of study treatment；
• The patient had developed or had concurrent malignant tumors within the past 3 years；
• Multiple factors that affect the oral administration of anlotinib (e.g., inability to swallow, post-gastrointestinal resection, chronic diarrhea, and intestinal obstruction) may affect the oral absorption of anlotinib；
• Uncontrolled pleural, pericardial, or ascites requiring repeated drainage (investigator judgment); Severe bone injury caused by tumor bone metastasis may occur or occur after enrollment；
• Patients whose imaging (CT or MRI) showed that the tumor had invaded the important blood vessels or the investigators judged that the tumor was likely to invade the important blood vessels and cause fatal hemorrhage during the follow-up study；
• Unmitigated toxic effects higher than CTCAE grade 1 due to any previous antineoplastic therapy, excluding alopecia；
• Major surgical treatment, open biopsy, or significant traumatic injury within 28 days before the first dose；
• A wound or fracture that has not healed for a long time；
• Patients with a history of arterial/venous thrombosis/cancer thrombosis within 6 months before the first dose of drug, such as cerebrovascular accident (including transient ischemic attack, cerebral hemorrhage, cerebral infarction), deep vein thrombosis and pulmonary embolism；
• People who have a history of psychotropic drug abuse and cannot abstain from it or have mental disorders；
• Subjects with any severe and/or uncontrolled illness；
• A history of vaccination with live attenuated vaccine within 28 days before the initiation of study treatment or a planned vaccination with live attenuated vaccine during the study；
• Patients with severe allergic disease, history of severe drug allergy, and known allergic to any component of the trial drug prescription;；
• Active autoimmune disease requiring systemic therapy (e.g., disease-modifying agents, corticosteroids, or immunosuppressive agents) had developed within 2 years before the initiation of study treatment；
• Patients who are diagnosed with immunodeficiency or who are receiving systemic glucocorticoid therapy or any other form of immunosuppressive therapy (at a dose of >10mg/ day of prednisone or other equivalent efficacy hormone) and continue to do so within 2 weeks before the first dose; Major surgical treatment or significant traumatic injury within 4 weeks before the first dose in this study；
• Participated in other clinical trials of antineoplastic drugs within 4 weeks before the first dose；
• Subjects with concomitant diseases that seriously endanger the safety of the subjects or interfere with the completion of the study, or those who were considered to be unsuitable for enrollment for other reasons according to the investigator's judgment.

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 · 61 центр

• Anhui Provincial Hospital — Хэфэй
• Fujian Cancer Hospital — Фучжоу
• First Hospital of Lanzhou University — Lanzhou
• Gansu Provincial Cancer Hospital — Lanzhou
• Sun Yat-sen Memorial Hospital — Гуанчжоу
• The First Affiliated Hospital of Jinan University — Гуанчжоу
• Huizhou Central People's Hospital — Huizhou
• Jiangmen Central Hospital — Jiangmen
• … и ещё 53 центра

Идентификаторы

NCT: NCT06475599 · TQB2450-III-13

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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