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

Sponsor
Peking Union Medical College
Study ID
NCT06145308
Phase
PHASE2
Status
Recruiting
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Conditions

  • Precision Therapy
  • Salivary Gland Carcinoma

Eligibility Criteria

Sex
ALL
Age
18 Years - 100 Years
Healthy Volunteers
Not accepted

Interventions

  • Cohort 1 (HER2-positive, RC48-ADC) — 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 1 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) — 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 1 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) — 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 1 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.
  • TROP2 ADC — 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 1 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.
  • TKI — 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 1 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.
  • Albumin-paclitaxel + platinum — 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 1 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.
  • Albumin-paclitaxel + carboplatin + apatinib + camrelizumab — 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 1 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.
  • albumin-bound paclitaxel+trastuzumab+pyrotinib — 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 1 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.
  • HER2,trastuzumab deruxtecan± pertuzumab — 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 1 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.
  • AR,AR antagonist ++ goserelin + pertuzumab + trastuzumab — 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 1 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.
  • AR,AR antagonist +goserelin +docetaxel — 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 1 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.
  • ivonescimab + investigator-choice platinum doublet+ — 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 1 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.
  • iparomlimab + tuvonralimab — 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 1 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.
  • cadonilimab — 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 1 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.
  • CDK4/6 inhibitor+AI or fulvestrant — 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 1 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.
  • alpelisib+fulvestrant — 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 1 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.
  • PARP inhibitor — 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 1 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.
  • enfortumab vedotin — 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 1 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.
  • HER2, pyrotinib + pertuzumab/trastuzumab — 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 1 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.
  • vebecotutamab ±lenvatinib — 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 1 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.

Study Details

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.

Key Dates

Start date
Aug 15, 2023
Status verified
Mar 2026
Primary completion
Jul 10, 2028
Completion
Jul 10, 2028

Study Design

Enrollment
39 participants (estimated)
Allocation
NON_RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: 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).
  • Experimental: Cohort 2 (NTRK-fusion or NTRK-mutant)
    larotrectinib 100 mg orally twice daily or entrectinib 600 mg orally once daily;
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: Cohort 5 (ACC-TKI)
    apatinib 250 mg qd po or anlotinib 12 mg
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: 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.
  • Experimental: Cohort 9 (HER2-positive, DS-8201 ± pertuzumab)
    trastuzumab deruxtecan 5.4 mg/kg IV q3w ± pertuzumab (loading 840 mg → 420 mg IV q3w).
  • Experimental: Cohort 10 (HER2+/AR+, AR antagonist + goserelin + pertuzumab + trastuzumab)
    Darolutamide 600mg po bid / Enzalutamide 160mg po qd / Apalutamide 240mg po qd / Rivarutamide 240mg po qd + goserelin 10.8 mg SC q12w + pertuzumab/trastuzumab loading 15 mL → 10 mL SC q3w.
  • Experimental: Cohort 11 (AR-positive, AR antagonist+ goserelin ± docetaxel)
    Darolutamide 600mg po bid / Enzalutamide 160mg po qd / Apalutamide 240mg po qd / Rivarutamide 240mg po qd+ goserelin 10.8 mg SC q12w ± docetaxel 75 mg/m² IV q3w.
  • Experimental: 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.
  • Experimental: Cohort 13 (iparomlimab + tuvonralimab)
    iparomlimab 5 mg/kg + platinum doublet (as above) ± bevacizumab 5 mg/kg IV q3w.
  • Experimental: Cohort 14 (cadonilimab)
    cadonilimab 10 mg/kg + platinum doublet (as above) ± bevacizumab 5 mg/kg IV q3w.
  • Experimental: 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
  • Experimental: Cohort 16 (PI3K-mutant)
    alpelisib 300 mg PO qd plus fulvestrant 500 mg IM q4w.
  • Experimental: 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).
  • Experimental: 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).
  • Experimental: Cohort 19 (HER2-positive, pyrotinib + pertuzumab + trastuzumab)
    pyrotinib 400 mg PO qd + pertuzumab/trastuzumab loading 15 mL → 10 mL SC q3w.
  • Experimental: ⑳ Cohort 20 (vebecotutamab ±lenvatinib):
    verbecotutamab 2.0 mg/kg ivgtt ± lenvatinib 8mg qd q3w

Primary Outcome Measure

ORR [ Time Frame: ORR at the end of Cycle 2 (each cycle is 21 days) ]

Central Contacts

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