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

Cancer Hospital, Chinese Academy of Medical Sciences/National Cancer Center of China

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.

Study Overview

• Status: Recruiting
• Conditions: Salivary Gland Carcinoma; Precision Therapy
• Intervention / Treatment: 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,AR antagonist ++ goserelin + pertuzumab + trastuzumab; Drug: AR,AR antagonist +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; Drug: vebecotutamab ±lenvatinib

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.

The diagnostic and prognostic value of fibroblast activation protein inhibitor (FAPI) PET/CT for salivary gland cancer: All patients undergo routine standard examinations (FDG PET/CT) and FAPI PET/CT before and after treatment. Two independent blinded reading teams separately evaluate the two sets of images to provide diagnosis, staging, and follow-up on patient prognosis.

• Study Type: Interventional
• Enrollment (Estimated): 39
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: fei Ma; Phone Number: 13910217780; Email: drmafei@126.com

Study Locations

• China
  • Beijing, China
    • Recruiting
    • National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College
    • Contact: Fei Ma, Dr.; Phone Number: 13718455257; Email: drmafei@126.com
  • Beijing Municipality
    • Beijing, Beijing Municipality, China, 100021
      • Recruiting
      • Fei Ma
      • Contact: Fei Ma, MD; Phone Number: +86-10-87787652; Email: drmafei@126.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

20

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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).	Drug: 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 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.; Other Names: HER2,Vedolizumab
Experimental: Cohort 2 (NTRK-fusion or NTRK-mutant); larotrectinib 100 mg orally twice daily or entrectinib 600 mg orally once daily;	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 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.; Other Names: NTRK-inhibitor
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.	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 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.; Other Names: AR,leuprolide + bicalutamide + abiraterone
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.	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 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.; Other Names: Cohort 4 (TROP2 ADC)
Experimental: Cohort 5 (ACC-TKI); apatinib 250 mg qd po or anlotinib 12 mg	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 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.; Other Names: Cohort 5 (ACC-TKI)
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.	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 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.; Other Names: Cohort 6 (albumin-bound paclitaxel + platinum)
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.	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 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.; Other Names: Cohort 7 (albumin-bound paclitaxel + carboplatin + apatinib + camrelizumab)
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.	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 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.; Other Names: Cohort8 (HER2-positive, albumin-bound paclitaxel + trastuzumab + pyrotinib)
Experimental: Cohort 9 (HER2-positive, DS-8201 ± pertuzumab); trastuzumab deruxtecan 5.4 mg/kg IV q3w ± pertuzumab (loading 840 mg → 420 mg IV q3w).	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 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.; Other Names: Cohort9(HER2-positive, DS-8201 ± pertuzumab)
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.	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 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.; Other Names: Cohort 12 (ivonescimab)
Experimental: Cohort 13 (iparomlimab + tuvonralimab); iparomlimab 5 mg/kg + platinum doublet (as above) ± bevacizumab 5 mg/kg IV q3w.	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 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.; Other Names: Cohort 13 (iparomlimab + tuvonralimab)
Experimental: Cohort 14 (cadonilimab); cadonilimab 10 mg/kg + platinum doublet (as above) ± bevacizumab 5 mg/kg IV q3w.	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 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.; Other Names: Cohort 14 (cadonilimab)
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	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 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.; Other Names: Cohort 15 (HR-positive)
Experimental: Cohort 16 (PI3K-mutant); alpelisib 300 mg PO qd plus fulvestrant 500 mg IM q4w.	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 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.; Other Names: Cohort 16 (PI3K-mutant)
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).	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 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.; Other Names: Cohort 17 (homologous-recombination-deficient)
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).	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 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.; Other Names: Cohort 18 (Nectin-4 ADC)
Experimental: Cohort 19 (HER2-positive, pyrotinib + pertuzumab + trastuzumab); pyrotinib 400 mg PO qd + pertuzumab/trastuzumab loading 15 mL → 10 mL SC q3w.	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 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.; Other Names: Cohort 19 (HER2-positive, pyrotinib + pertuzumab + trastuzumab)
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.	Drug: AR,AR antagonist ++ 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 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.; Other Names: Cohort 10 (HER2+/AR+, AR antagonist + goserelin + pertuzumab + trastuzumab)
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.	Drug: AR,AR antagonist +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 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.; Other Names: Cohort 11 (AR-positive, AR antagonist + goserelin ± docetaxel)
Experimental: ⑳ Cohort 20 (vebecotutamab ±lenvatinib): verbecotutamab 2.0 mg/kg ivgtt ± lenvatinib 8mg qd q3w	Drug: vebecotutamab ±lenvatinib; 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.; Other Names: Cohort 20 (vebecotutamab ±lenvatinib)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
ORR	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	ORR at the end of Cycle 2 (each cycle is 21 days)

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Peking Union Medical College
• Collaborators: Peking University Hospital of Stomatology
• Investigators: Principal Investigator: Jie Zhang, Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2023
• Primary Completion (Estimated): July 10, 2028
• Study Completion (Estimated): July 10, 2028

Study Registration Dates

• First Submitted: September 7, 2023
• First Submitted That Met QC Criteria: November 21, 2023
• First Posted (Actual): November 24, 2023

Study Record Updates

• Last Update Posted (Actual): April 2, 2026
• Last Update Submitted That Met QC Criteria: March 27, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Mouth Diseases; Stomatognathic Diseases; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Salivary Gland Diseases; Mouth Neoplasms; Salivary Gland Neoplasms; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Enzyme Inhibitors; Hormone Antagonists; Androgen Antagonists; Pituitary Hormone-Releasing Hormones; Hypothalamic Hormones; Peptide Hormones; Neuropeptides; Peptides; Amino Acids, Peptides, and Proteins; Oligopeptides; Nerve Tissue Proteins; Proteins; Organic Chemicals; Pharmacologic Actions; Chemical Actions and Uses; Therapeutic Uses; Hydrocarbons; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Polycyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Inorganic Chemicals; Coordination Complexes; Taxoids; Cyclodecanes; Diterpenes; Steroids; Fused-Ring Compounds; Elements; Metals; Metals, Heavy; Estradiol; Estrenes; Estranes; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Transition Elements; Albumins; Paclitaxel; Gonadotropin-Releasing Hormone; Trastuzumab; Fulvestrant; Albumin-Bound Paclitaxel; Poly(ADP-ribose) Polymerase Inhibitors; Carboplatin; Leuprolide; Goserelin; Androgen Receptor Antagonists; abiraterone; pertuzumab; Platinum; enfortumab vedotin; camrelizumab; apatinib; pyrotinib; bicalutamide
• Other Study ID Numbers: NCC4132

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No