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

NCT05898373 | Not Yet Recruiting Phase 1

• 1 other identifier: NCC4001
• Study Type: interventional
• Target: 120
• Locations: 0 countries
• Sites: N/A

Brief Summary

(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.

Conditions

Salivary Gland Cancer

Outcome Measures

Primary Outcomes (1)

• ORR

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

  8 weeks

Secondary Outcomes (5)

• PFS

  2 years

• DFS

  2 years

• OS

  2 years

• complete resection rate

  2 years

• Rate of facial nerve preservation

  2 years

Study Arms (4)

vedicitumomab

EXPERIMENTAL

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

Drug: vedicitumomab (Edisil, RC48）

vedicitumomab in combination with pyrrolizidine

EXPERIMENTAL

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

Drug: vedicitumomab in combination with pyrrolizidine

RC48 in combination with a platinum-based chemotherapeutic agent

EXPERIMENTAL

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

Drug: RC48 in combination with a platinum-based chemotherapeutic agent

RC48 in combination with teraplizumab

EXPERIMENTAL

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

Drug: RC48 in combination with teraplizumab

Interventions

vedicitumomab (Edisil, RC48） DRUG

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

vedicitumomab in combination with pyrrolizidine DRUG

vedicitumomab in combination with pyrrolizidine

vedicitumomab in combination with pyrrolizidine

RC48 in combination with a platinum-based chemotherapeutic agent DRUG

RC48 in combination with a platinum-based chemotherapeutic agent

RC48 in combination with a platinum-based chemotherapeutic agent

RC48 in combination with teraplizumab DRUG

RC48 in combination with teraplizumab

RC48 in combination with teraplizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• (1) Patients with advanced metastatic salivary gland ductal carcinoma diagnosed histopathologically at the primary site or metastasis; (2) Original paraffin-embedded tumor tissue stained for HER2 at diagnosis, either HER2 1+/HER2 2+/HER2 3+, previous test results (confirmed by the investigator) or test results from the study center are acceptable; (3) ECOG physical status 0 or 1 within 3 days prior to the first dose of study treatment; (4) 18 years of age or older - upper limit; (5) Life expectancy greater than 3 months according to RECIST 1.1 criteria; (6) At least one measurable lesion; and (7) a score of 0 or 1 for ECOG physical status within 3 days prior to the first dose of study treatment. status 0 or 1 within 3 days prior to the first dose of study treatment; ④ 18 years of age or older - no upper limit; ⑤ life expectancy greater than 3 months; ⑥ at least one measurable lesion according to RECIST 1.1 criteria;(7) Female subjects should be surgically sterilized, post-menopausal, or agree to use at least one medically approved contraceptive (e.g., IUD, pill, or condom) during and for 6 months after the study treatment period, and must have a negative blood pregnancy test within 7 days prior to study entry and must be non-lactating. Male subjects should agree to use at least one medically approved contraceptive measure during the study treatment period and for 6 months after the end of the study treatment period; ⑧ Patients must have adequate liver, kidney, bone marrow, heart and lung organ function: bone marrow function: (1) hemoglobin ≥ 90 g/L; (2) absolute neutrophil count ≥ 1.5 × 109/L; (3) platelets ≥ 100 × 109/L Liver function (based on the normal value of the clinical trial center): (1) without liver metastases, serum total bilirubin ≤ 1.5 times ULN; with liver metastases, serum total bilirubin ≤ 3 times ULN (2) without liver metastases, ALT and AST are ≤ 3 times ULN, with liver metastases, ALT and AST are ≤ 5 times ULN Kidney function (based on the normal value of the clinical trial center): (1) blood creatinine ≤ 1.5 times ULN, or 1.5 times ULN, or Cockcroft-Gault formula calculated creatinine clearance (CrCl) ≥ 60 mL/min, or measured 24-hour urine CrCl ≥ 60 mL/min; cardiac function: (1) New York Heart Association (NYHA) classification \<3 (2) left ventricular ejection fraction ≥ 50%

You may not qualify if:

• (i) treatment with an investigational drug or other antibody-coupled drug targeting HER2 at the start of the study drug; (ii) major surgery within 4 weeks prior to the start of the study drug and incomplete recovery; (iii) live vaccination within 4 weeks prior to the start of the study drug or any vaccine planned during the study period (except novel coronavirus vaccine);(iv) an arterial/venous thrombotic event such as cerebrovascular accident (including temporary ischemic attack), deep vein thrombosis, or pulmonary embolism within 6 months prior to study drug administration; (v) major cardiovascular disease (NYHA class 3 or 4 heart failure, second degree or greater heart block, myocardial infarction within the past 12 months, unstable arrhythmia or unstable angina, cerebral infarction within 6 months, etc.); (vi) ongoing unstable controlled systemic disease, including diabetes, hypertension, pulmonary fibrosis, acute lung disease, interstitial lung disease, cirrhosis, etc;(7) Active infection requiring systemic therapy; (8) History of active tuberculosis; (9) Positive human immunodeficiency virus (HIV) test result; (10) Positive hepatitis B surface antigen (HBsAg) with an HBV DNA copy number greater than the upper limit of normal values in the laboratory department of the study center; or (11) Positive hepatitis C virus (HCV) antibody with an HCV RNA copy number greater than the upper limit of normal values in the laboratory department of the study center; or (12) Positive hepatitis C virus (HCV) antibody with an HCV RNA copy number greater than the upper limit of normal values in the laboratory department of the study center. ⑪Conditions that, in the opinion of the investigator, may affect the safety or compliance with the study drug therapy, including but not limited to large pleural/peritoneal/pericardial effusions, uncorrectable pleural/peritoneal/pericardial effusions, psychiatric disorders, etc. ⑪Known hypersensitivity or delayed hypersensitivity to certain components of the recombinant humanized anti-HER2 monoclonal antibody-MMAE coupling agent vedicizumab (Edisil, RC48) for injection or similar drugs Hypersensitivity or delayed hypersensitivity reactions; ⑬Women who are pregnant or breastfeeding or women/men who are planning to have children

Sponsors & Collaborators

• Peking Union Medical College: lead

MeSH Terms

Conditions

Salivary Gland Neoplasms

Interventions

RC48 antibody

Condition Hierarchy (Ancestors)

Mouth Neoplasms; Head and Neck Neoplasms; Neoplasms by Site; Neoplasms; Mouth Diseases; Stomatognathic Diseases; Salivary Gland Diseases

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Department of Internal Medicine, Cancer Hospital, Chinese Academy of Medical Sciences

Study Record Dates

• First Submitted: May 15, 2023
• First Posted: June 12, 2023
• Study Start: June 7, 2023
• Primary Completion: June 6, 2025
• Study Completion: June 6, 2026
• Last Updated: June 12, 2023

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share