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

NCT ID: NCT06145308

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 39 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-15
• Study Completion Date: 2028-07-10

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.

Conditions

Salivary Gland Carcinoma; Precision Therapy

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

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).

Group Type: EXPERIMENTAL

Cohort 1 (HER2-positive, RC48-ADC)

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Cohort 2 (NTRK-fusion or NTRK-mutant)

larotrectinib 100 mg orally twice daily or entrectinib 600 mg orally once daily;

Group Type: EXPERIMENTAL

Cohort 2 (NTRK-fusion or NTRK-mutant)

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

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.

Group Type: EXPERIMENTAL

Cohort 3 (AR-positive, leuprolide + bicalutamide + abiraterone)

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

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.

Group Type: EXPERIMENTAL

TROP2 ADC

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Cohort 5 (ACC-TKI)

apatinib 250 mg qd po or anlotinib 12 mg

Group Type: EXPERIMENTAL

TKI

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

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.

Group Type: EXPERIMENTAL

Albumin-paclitaxel + platinum

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

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.

Group Type: EXPERIMENTAL

Albumin-paclitaxel + carboplatin + apatinib + camrelizumab

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

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.

Group Type: EXPERIMENTAL

albumin-bound paclitaxel+trastuzumab+pyrotinib

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Cohort 9 (HER2-positive, DS-8201 ± pertuzumab)

trastuzumab deruxtecan 5.4 mg/kg IV q3w ± pertuzumab (loading 840 mg → 420 mg IV q3w).

Group Type: EXPERIMENTAL

HER2,trastuzumab deruxtecan± pertuzumab

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

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.

Group Type: EXPERIMENTAL

AR,darolutamide + goserelin+pertuzumab/trastuzumab

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Cohort 11 (AR-positive, darolutamide + goserelin + docetaxel)

darolutamide 600 mg PO bid + goserelin 10.8 mg SC q12w + docetaxel 75 mg/m² IV q3w.

Group Type: EXPERIMENTAL

AR,darolutamide +goserelin +docetaxel

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

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.

Group Type: EXPERIMENTAL

ivonescimab + investigator-choice platinum doublet+

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Cohort 13 (iparomlimab + tuvonralimab)

iparomlimab 5 mg/kg + platinum doublet (as above) ± bevacizumab 5 mg/kg IV q3w.

Group Type: EXPERIMENTAL

iparomlimab + tuvonralimab

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Cohort 14 (cadonilimab)

cadonilimab 10 mg/kg + platinum doublet (as above) ± bevacizumab 5 mg/kg IV q3w.

Group Type: EXPERIMENTAL

cadonilimab

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

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

Group Type: EXPERIMENTAL

CDK4/6 inhibitor+AI or fulvestrant

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Cohort 16 (PI3K-mutant)

alpelisib 300 mg PO qd plus fulvestrant 500 mg IM q4w.

Group Type: EXPERIMENTAL

alpelisib+fulvestrant

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

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).

Group Type: EXPERIMENTAL

PARP inhibitor

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

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).

Group Type: EXPERIMENTAL

enfortumab vedotin

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Cohort 19 (HER2-positive, pyrotinib + pertuzumab + trastuzumab)

pyrotinib 400 mg PO qd + pertuzumab/trastuzumab loading 15 mL → 10 mL SC q3w.

Group Type: EXPERIMENTAL

HER2, pyrotinib + pertuzumab/trastuzumab

Intervention Type: DRUG

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Interventions

Cohort 1 (HER2-positive, RC48-ADC)

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

Cohort 2 (NTRK-fusion or NTRK-mutant)

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

Cohort 3 (AR-positive, leuprolide + bicalutamide + abiraterone)

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

TROP2 ADC

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

TKI

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

Albumin-paclitaxel + platinum

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

Albumin-paclitaxel + carboplatin + apatinib + camrelizumab

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

albumin-bound paclitaxel+trastuzumab+pyrotinib

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

HER2,trastuzumab deruxtecan± pertuzumab

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

AR,darolutamide + goserelin+pertuzumab/trastuzumab

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

AR,darolutamide +goserelin +docetaxel

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

ivonescimab + investigator-choice platinum doublet+

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

iparomlimab + tuvonralimab

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

cadonilimab

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

CDK4/6 inhibitor+AI or fulvestrant

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

alpelisib+fulvestrant

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

PARP inhibitor

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

enfortumab vedotin

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

HER2, pyrotinib + pertuzumab/trastuzumab

Neoadjuvant / conversion phase: After 2-6 cycles of protocol therapy, patients are re-evaluated. Those deemed resectable undergo surgery of the primary tumour ± metastatic sites, followed by radiotherapy or other modalities (e.g., radiofrequency ablation) at the investigator's discretion. Patients who remain unresectable after six cycles continue the same regimen until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to stop.

Adjuvant phase: Treatment is administered for 2 years, or until intolerable toxicity or withdrawal of consent.

Salvage phase: Therapy continues until disease progression, intolerable toxicity, withdrawal of consent, or investigator decision to terminate.

Intervention Type: DRUG

Other Intervention Names

HER2,Vedolizumab; NTRK-inhibitor; AR,leuprolide + bicalutamide + abiraterone; Cohort 4 (TROP2 ADC); Cohort 5 (ACC-TKI); Cohort 6 (albumin-bound paclitaxel + platinum); Cohort 7 (albumin-bound paclitaxel + carboplatin + apatinib + camrelizumab); Cohort8 (HER2-positive, albumin-bound paclitaxel + trastuzumab + pyrotinib); Cohort9(HER2-positive, DS-8201 ± pertuzumab); Cohort 10 (HER2+/AR+, darolutamide + goserelin + pertuzumab + trastuzumab); Cohort 11 (AR-positive, darolutamide + goserelin + docetaxel); Cohort 12 (ivonescimab); Cohort 13 (iparomlimab + tuvonralimab); Cohort 14 (cadonilimab); Cohort 15 (HR-positive); Cohort 16 (PI3K-mutant); Cohort 17 (homologous-recombination-deficient); Cohort 18 (Nectin-4 ADC); Cohort 19 (HER2-positive, pyrotinib + pertuzumab + trastuzumab)

Eligibility Criteria

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;

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 100 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Peking University Hospital of Stomatology

OTHER

Sponsor Role: collaborator

Peking Union Medical College

OTHER

Sponsor Role: lead

Responsible Party

Fei Ma

Chief physician and deputy chief of internal medicine

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Jie Zhang

Role: PRINCIPAL_INVESTIGATOR

Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology

Locations

Fei Ma

Beijing, Beijing Municipality, China

Site Status: RECRUITING

National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

fei Ma

Role: CONTACT

drmafei@126.com

13910217780

Facility Contacts

Fei Ma, MD

Role: primary

mafei@126.com

+86-10-87787652

Fei Ma, Dr.

Role: primary

drmafei@126.com

13910217780

Other Identifiers

NCC4132

Identifier Type: -

Identifier Source: org_study_id