Precision Treatment of Recurrent/Metastatic Salivary Gland Carcinoma Guided by Molecular Typing

Phase 2

Recruiting

• Conditions: Salivary Gland Carcinoma; Precision Therapy
• Interventions: Drug: Cohort 1 (HER2-positive, RC48-ADC); Drug: Cohort 2 (NTRK-fusion or NTRK-mutant); Drug: Cohort 3 (AR-positive, leuprolide + bicalutamide + abiraterone); Drug: TROP2 ADC; Drug: TKI; Drug: Albumin-paclitaxel + platinum; Drug: Albumin-paclitaxel + carboplatin + apatinib + camrelizumab; Drug: albumin-bound paclitaxel+trastuzumab+pyrotinib; Drug: HER2,trastuzumab deruxtecan± pertuzumab; Drug: AR,darolutamide + goserelin+pertuzumab/trastuzumab; Drug: AR,darolutamide +goserelin +docetaxel; Drug: ivonescimab + investigator-choice platinum doublet+; Drug: iparomlimab + tuvonralimab; Drug: cadonilimab; Drug: CDK4/6 inhibitor+AI or fulvestrant; Drug: alpelisib+fulvestrant; Drug: PARP inhibitor; Drug: enfortumab vedotin; Drug: HER2, pyrotinib + pertuzumab/trastuzumab

• Registration Number: NCT06145308
• Lead Sponsor: Peking Union Medical College

Brief Summary

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.

Detailed Description

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.

To investigate concordance between drug-sensitivity testing using ex-vivo 3D tumour models and actual clinical outcomes, and to guide later-line treatment selection based on drug-sensitivity results.

Study Timeline

• Study Start: 2023-08-15
• Study First Submitted: 2023-09-07
• Study First Submitted QC: 2023-11-21
• Study First Posted: 2023-11-24
• Status Verified: 2024-12
• Last Update Submitted: 2025-09-08
• Last Update Posted: 2025-09-15
• Primary Completion: 2026-07-10
• Study Completion: 2028-07-10

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 39

Inclusion Criteria

• 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.

Exclusion Criteria

• 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;

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cohort 1 (HER2-positive, RC48-ADC)	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).
Cohort 2 (NTRK-fusion or NTRK-mutant)	Cohort 2 (NTRK-fusion or NTRK-mutant)	larotrectinib 100 mg orally twice daily or entrectinib 600 mg orally once daily;
Cohort 3 (AR-positive, leuprolide + bicalutamide + abiraterone)	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.
Cohort 4 (TROP2 ADC)	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.
Cohort 5 (ACC-TKI)	TKI	apatinib 250 mg qd po or anlotinib 12 mg
Cohort 6 (albumin-bound paclitaxel + platinum)	Albumin-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.
Cohort 7 (albumin-bound paclitaxel + carboplatin + apatinib + camrelizumab)	Albumin-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.
Cohort 8 (HER2-positive, albumin-bound paclitaxel + trastuzumab + pyrotinib)	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.
Cohort 9 (HER2-positive, DS-8201 ± pertuzumab)	HER2,trastuzumab deruxtecan± pertuzumab	trastuzumab deruxtecan 5.4 mg/kg IV q3w ± pertuzumab (loading 840 mg → 420 mg IV q3w).
Cohort 10 (HER2+/AR+, darolutamide + goserelin + pertuzumab + trastuzumab)	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.
Cohort 11 (AR-positive, darolutamide + goserelin + docetaxel)	AR,darolutamide +goserelin +docetaxel	darolutamide 600 mg PO bid + goserelin 10.8 mg SC q12w + docetaxel 75 mg/m² IV q3w.
Cohort 12 (ivonescimab)	ivonescimab + investigator-choice platinum doublet+	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.
Cohort 13 (iparomlimab + tuvonralimab)	iparomlimab + tuvonralimab	iparomlimab 5 mg/kg + platinum doublet (as above) ± bevacizumab 5 mg/kg IV q3w.
Cohort 14 (cadonilimab)	cadonilimab	cadonilimab 10 mg/kg + platinum doublet (as above) ± bevacizumab 5 mg/kg IV q3w.
Cohort 15 (HR-positive)	CDK4/6 inhibitor+AI or fulvestrant	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
Cohort 16 (PI3K-mutant)	alpelisib+fulvestrant	alpelisib 300 mg PO qd plus fulvestrant 500 mg IM q4w.
Cohort 17 (homologous-recombination-deficient)	PARP inhibitor	PARP inhibitor (olaparib 300 mg PO bid, niraparib 300 mg PO qd, fluzoparib 150 mg PO bid, or pamiparib 60 mg PO bid).
Cohort 18 (Nectin-4 ADC)	enfortumab vedotin	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).
Cohort 19 (HER2-positive, pyrotinib + pertuzumab + trastuzumab)	HER2, pyrotinib + pertuzumab/trastuzumab	pyrotinib 400 mg PO qd + pertuzumab/trastuzumab loading 15 mL → 10 mL SC q3w.

Primary Outcome Measures

Name	Time	Method
ORR	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

Secondary Outcome Measures

Name	Time	Method
R0 resection rate;	R0 resection rate at the end of surgical treatment	R0 resection rate in patients who received neoadjuvant and translational therapy and then underwent surgery
DFS	DFS rates at 3-year	3-year DFS rates for patients who underwent surgery
OS	OS rate at 5-year	OS for all patients
MPR;	MPR rate at the end of surgical treatment	MPR rates in patients who received neoadjuvant and translational therapy and then underwent surgery
Facial nerve protection rate	Facial nerve protection rate at the end of surgical treatment	Facial nerve protection rate in patients who received neoadjuvant and translational therapy and then underwent surgery
PFS;	PFS Rate at 2-Year	2-Year PFS Rate for Patients Receiving Rescue Therapy

Trial Locations

Locations (2)

Fei Ma; 🇨🇳 Beijing, Beijing Municipality, China

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College; 🇨🇳 Beijing, China