Cancer Hospital, Chinese Academy of Medical Sciences/National Cancer Center of China
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 发起方
- 入组人数
- 39
- 试验地点
- 2
- 主要终点
- ORR
研究概览
简要总结
Patients with salivary gland carcinoma were divided into groups according to HER2, NTRK, AR, TROP-2, etc. Patients in different groups were given precision targeted therapy or chemotherapy to evaluate the efficacy (ORR rate) and safety of precision therapy.
详细描述
Patients with locally advanced/recurrent or oligometastatic salivary gland carcinoma will be stratified by HER2, NTRK, AR, TROP-2, etc., and receive precision-targeted or chemotherapy regimens, with efficacy (objective response rate, etc.) and safety of neoadjuvant/conversion therapy evaluated.
To assess the efficacy of post-operative adjuvant therapy guided by minimal residual disease (MRD) testing in locally advanced salivary gland carcinoma.
Patients with locally advanced/recurrent or symptomatic, rapidly progressive metastatic salivary gland carcinoma who are intolerant of or refuse surgery and radiotherapy will be molecularly stratified and treated with precision regimens, with efficacy (objective response rate, etc.) and safety of salvage therapy evaluated.
To evaluate efficacy (objective response rate, etc.) and safety of later-line therapy for locally advanced/recurrent or distant metastatic salivary gland carcinoma.
Using multi-omic approaches to explore salivary gland carcinoma heterogeneity and biomarkers associated with recurrence, metastasis, treatment response and prognosis.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Participant)
入排标准
- 年龄范围
- 18 Years 至 100 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients with histopathologic diagnosis of salivary gland carcinoma
- •The tumor tissues were subjected to HER2/NTRK/AR/TROP-2 immunohistochemical staining.
- •ECOG physical status 0 or 1 score in the 3 days before the first medication of the study treatment;
- •Age 18 or older - no upper limit;
- •Life expectancy is more than 3 months; ⑥Have at least one measurable lesion according to RECIST1.1 standards; ⑦Women of childbearing age must have a negative pregnancy test within 7 days before the first medication, and agree to receive the necessary contraceptive measures;
- •⑧The patient must have adequate liver, kidney, bone marrow, heart and lung and other organ functions:
- •⑨Understanding and voluntarily signing informed consent prior to performing any research-related evaluation/operation;
- •⑩Ability to comply with research visit schedules and other programmatic requirements.
排除标准
- •Known hypersensitivity or delayed anaphylaxis to any agents in this trial;
- •Major surgery had been performed within 4 weeks prior to the start of the study and did not fully recover;
- •Have received a live vaccine within 4 weeks before the start of the study or plan to receive any vaccine during the study period ;
- •To study the occurrence of arterial/venous thrombosis events within 6 months before medication;
- •Major cardiovascular diseases;
- •Is suffering from uncontrolled systemic diseases, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, cirrhosis, etc.;
- •Is suffering from an active infection that requires systemic treatment;
- •History of active tuberculosis; ⑨ Positive human immunodeficiency virus (HIV) test result; ⑩ Patients with chronic hepatitis B or active hepatitis C. ⑪Conditions that the investigator believes will affect the safety or compliance of the drug therapy in this study ⑫Female/male who is pregnant or breastfeeding or who intends to give birth;
研究组 & 干预措施
Cohort 1 (HER2-positive, RC48-ADC)
Disitamab vedotin 2.5 mg/kg will be administered as an intravenous infusion every 2 weeks (Q2W) as monotherapy, or in combination with physician-selected platinum-based chemotherapy (carboplatin 200-250 mg/m² IV Q2W or cisplatin 50 mg/m² IV Q2W).
干预措施: Cohort 1 (HER2-positive, RC48-ADC) (Drug)
Cohort 2 (NTRK-fusion or NTRK-mutant)
larotrectinib 100 mg orally twice daily or entrectinib 600 mg orally once daily;
干预措施: Cohort 2 (NTRK-fusion or NTRK-mutant) (Drug)
Cohort 3 (AR-positive, leuprolide + bicalutamide + abiraterone)
leuprolide 3.75 mg subcutaneously every 4 weeks, bicalutamide 50 mg orally once daily, and abiraterone 1 000 mg orally once daily.
干预措施: Cohort 3 (AR-positive, leuprolide + bicalutamide + abiraterone) (Drug)
Cohort 4 (TROP2 ADC)
ESG401 16 mg/kg IV (days 1, 8, 15, q4w), sacituzumab govitecan 10 mg/kg IV (days 1 & 8, q3w), or sacituzumab tirumotecan 5 mg/kg IV q2w.
干预措施: TROP2 ADC (Drug)
Cohort 5 (ACC-TKI)
apatinib 250 mg qd po or anlotinib 12 mg
干预措施: TKI (Drug)
Cohort 6 (albumin-bound paclitaxel + platinum)
albumin-bound paclitaxel 260 mg/m² IV q3w plus physician-selected cisplatin 75 mg/m² IV q3w or carboplatin 350 mg/m² IV q3w.
干预措施: Albumin-paclitaxel + platinum (Drug)
Cohort 7 (albumin-bound paclitaxel + carboplatin + apatinib + camrelizumab)
albumin-bound paclitaxel 260 mg/m² IV q3w, carboplatin 350 mg/m² IV q3w, camrelizumab 200 mg IV q3w, and apatinib 250 mg qd po.
干预措施: Albumin-paclitaxel + carboplatin + apatinib + camrelizumab (Drug)
Cohort 8 (HER2-positive, albumin-bound paclitaxel + trastuzumab + pyrotinib)
albumin-bound paclitaxel 260 mg/m² + trastuzumab (loading 8 mg/kg → 6 mg/kg IV q3w) + pyrotinib 400 mg PO qd.
干预措施: albumin-bound paclitaxel+trastuzumab+pyrotinib (Drug)
Cohort 9 (HER2-positive, DS-8201 ± pertuzumab)
trastuzumab deruxtecan 5.4 mg/kg IV q3w ± pertuzumab (loading 840 mg → 420 mg IV q3w).
干预措施: HER2,trastuzumab deruxtecan± pertuzumab (Drug)
Cohort 10 (HER2+/AR+, darolutamide + goserelin + pertuzumab + trastuzumab)
darolutamide 600 mg PO bid + goserelin 10.8 mg SC q12w + pertuzumab/trastuzumab loading 15 mL → 10 mL SC q3w.
干预措施: AR,darolutamide + goserelin+pertuzumab/trastuzumab (Drug)
Cohort 11 (AR-positive, darolutamide + goserelin + docetaxel)
darolutamide 600 mg PO bid + goserelin 10.8 mg SC q12w + docetaxel 75 mg/m² IV q3w.
干预措施: AR,darolutamide +goserelin +docetaxel (Drug)
Cohort 12 (ivonescimab)
ivonescimab 20 mg/kg + investigator-choice platinum doublet (albumin-paclitaxel 260 mg/m², liposomal paclitaxel 175 mg/m², docetaxel 75 mg/m², or vinorelbine 25 mg/m² d1,d8) plus cisplatin 75 mg/m² or carboplatin AUC 5-6 IV q3w.
干预措施: ivonescimab + investigator-choice platinum doublet+ (Drug)
Cohort 13 (iparomlimab + tuvonralimab)
iparomlimab 5 mg/kg + platinum doublet (as above) ± bevacizumab 5 mg/kg IV q3w.
干预措施: iparomlimab + tuvonralimab (Drug)
Cohort 14 (cadonilimab)
cadonilimab 10 mg/kg + platinum doublet (as above) ± bevacizumab 5 mg/kg IV q3w.
干预措施: cadonilimab (Drug)
Cohort 15 (HR-positive)
CDK4/6 inhibitor (abemaciclib 150 mg PO bid or palbociclib 125 mg PO qd) plus AI (letrozole 2.5 mg, anastrozole 1 mg, or exemestane 20 mg PO qd) or fulvestrant 500 mg IM q4w
干预措施: CDK4/6 inhibitor+AI or fulvestrant (Drug)
Cohort 16 (PI3K-mutant)
alpelisib 300 mg PO qd plus fulvestrant 500 mg IM q4w.
干预措施: alpelisib+fulvestrant (Drug)
Cohort 17 (homologous-recombination-deficient)
PARP inhibitor (olaparib 300 mg PO bid, niraparib 300 mg PO qd, fluzoparib 150 mg PO bid, or pamiparib 60 mg PO bid).
干预措施: PARP inhibitor (Drug)
Cohort 18 (Nectin-4 ADC)
enfortumab vedotin 1.25 mg/kg IV d1,d8,d15 (max 125 mg) ± ICI (pembrolizumab 200 mg, camrelizumab 200 mg, or toripalimab 240 mg IV q3w).
干预措施: enfortumab vedotin (Drug)
Cohort 19 (HER2-positive, pyrotinib + pertuzumab + trastuzumab)
pyrotinib 400 mg PO qd + pertuzumab/trastuzumab loading 15 mL → 10 mL SC q3w.
干预措施: HER2, pyrotinib + pertuzumab/trastuzumab (Drug)
结局指标
主要结局
ORR
时间窗: ORR at the end of Cycle 2 (each cycle is 21 days)
ORR rates for neoadjuvant and translational therapy in patients with locally advanced/recurrent and advanced oligometastatic salivary gland cancer and ORR rate of salvage therapy for locally advanced/recurrent or distantly metastatic salivary gland carcinoma with rapid progression that cannot tolerate or refuses surgery
次要结局
- DFS(DFS rates at 3-year)
- OS(OS rate at 5-year)
- MPR;(MPR rate at the end of surgical treatment)
- Facial nerve protection rate(Facial nerve protection rate at the end of surgical treatment)
- R0 resection rate;(R0 resection rate at the end of surgical treatment)
- PFS;(PFS Rate at 2-Year)
研究者
Fei Ma
Chief physician and deputy chief of internal medicine
Peking Union Medical College