Neoplasms

All Conditions

Mouth and Tooth Diseases

Rare Diseases

Carcinoma

Carcinoma, Ductal

Salivary Gland Neoplasms

Mouth Neoplasms

Head and Neck Neoplasms

Mouth Diseases

Stomatognathic Diseases

Salivary Gland Diseases

Oral Cancer

All Drugs and Chemicals

Antineoplastic Agents

Antibodies

Antibodies, Monoclonal

Trastuzumab

Carboplatin

Immune Checkpoint Inhibitors

Cisplatin

Immunoglobulins

RC48 (2.5 mg/kg every two weeks) intravenously for 6-8 cycles

RC48 （2 mg/kg every two weeks) intravenously for 6-8 cycles in combination with oral HER2 TKI (pyrrolizidine 400 mg qd po)

RC48 (2 mg/kg every two weeks) in combination with a platinum-based chemotherapeutic agent of the physician's choice (carboplatin 200-250 mg/m2 every two weeks or cisplatin 50 mg/m2 every two weeks) administered intravenously for 6-8 cycles

RC48(2 mg/kg every two weeks) in combination with an immune checkpoint inhibitor (teraplizumab, 3 mg/kg every two weeks)

intravenously for 6-8 cycles before surgery and postoperative radiotherapy, followed by Treatment with injectable recombinant humanized anti-HER2 monoclonal antibody-MMAE coupling agent vedicitumomab (Edisil, RC48) until 1 year or disease progression or intolerable toxicity in locally advanced patients , and until disease progression or intolerable toxicity in metastatic patients .

vedicitumomab (Edisil, RC48）

vedicitumomab in combination with pyrrolizidine

RC48 in combination with a platinum-based chemotherapeutic agent

RC48 in combination with teraplizumab

(1) To apply Bayesian statistics to screen for the most effective treatment regimen containing recombinant humanized anti-HER2 monoclonal antibody-MMAE coupling agent vedicitumomab (Edisil, RC48) for locally advanced or metastatic salivary gland ductal carcinoma expressing HER2 in the near future. (2) To explore biomarkers relevant to the efficacy of recombinant humanized anti-HER2 monoclonal antibody-MMAE-coupled vedicitumomab (Edisil, RC48) in the treatment of HER2-expressing locally advanced or metastatic salivary gland ductal carcinoma.

Using a Bayesian adaptation method based on posterior probabilities, patients will be randomized into four cohorts as follows:

(i) Cohort 1 (RC48 monotherapy group, control group): vedicitumomab monotherapy (2.5 mg/kg, intravenous, Q2w); (ii) Cohort 2 (RC48 + pyrrolitinib group): vedicitumomab (Edexcel, RC48) (2 mg/kg, sedation, Q2w) combined with an oral HER2 TKI (pyrrolitinib 400 mg po qd ); (iii) Cohort 3 (RC48 + platinum group): vedicitumomab (2mg/kg, IV, Q2w) in combination with a physician's choice of platinum-based chemotherapy (carboplatin 200-250mg/m2, IV, Q2w or cisplatin 50mg/m2, IV, Q2w); (iv) Cohort 4 (RC48 + Tremelimumab group): vedicitumomab (2mg/kg, IV, Q2w) in combination with the immune checkpoint inhibitor tremelimumab (3mg/kg, IV, Q2w);

In this study, we will detect HER2 immunohistochemistry, HER2FISH (HER2/CEP17), androgen receptor AR, value-added index ki67, human epidermal growth factor EGFR, basal cytokeratin CK5/6, immune checkpoint PD-L1, type 4 mucin MUC4, recombinant human RAS-related protein, etc. in pre-treatment specimens using traditional immunohistochemistry methods. 5ARAB5A, tumor infiltrating lymphocytes TILs, regulatory T cells Treg and other immune cells, circulating tumor cell DNA (ctDNA) by NGS, blood count, lymphocyte subsets, and HER2 ECD by ELISA. Patients with locally advanced disease were divided into pCR group (complete remission group) and non-pCR group (non-complete remission group) according to their clinical response to treatment, and patients with advanced metastatic disease were divided into PD group (disease progression group) and non-PD group (non-progression group), comparing the differences between the pCR and non-pCR groups, and the differences between the PD and non-PD groups, and exploring the differences with vedicizumab (Edisil, RC48) in monotherapy or combination for salivary gland ductal carcinoma.

Vedicitumomab Alone or in Combination for the Treatment of Locally Advanced or Metastatic SDC

Phase II, Multi-arm, Open Clinical Study of Recombinant Humanized Anti-HER2 Monoclonal Antibody-MMAE Coupling Agent Vedicitumomab Alone or in Combination for the Treatment of Locally Advanced or Metastatic Salivary Gland Ductal Carcinoma

ORR definition: the proportion of patients with tumor volume reduction to pre-specified values (CR/PR) who can maintain the minimum time requirement

PFS definition: the time from the start of randomization (or the start of treatment in a single-arm trial) to tumor progression or death from any cause, whichever occurs first;

disease-free survival (DFS) definition: is the time from the start of randomization (or the start of treatment in a single-arm trial) to disease recurrence or death from any cause (whichever occurs first)

OS defined as means the time from the start of randomization (or the start of treatment in a single-arm trial) to death from any cause

complete resection rate: lesion R0 resection and no extraperitoneal invasion of lymph nodes, no positive lymph on residual

Rate of facial nerve preservation: the proportion of patients whose facial nerve was originally judged by the surgeon to require surgical resection and who were able to preserve the facial nerve as a result of neoadjuvant or conversion therapy.

Spots Global Cancer Trial Database for vedicitumomab in combination with pyrrolizidine