Trial Title:
Vedicitumomab Alone or in Combination for the Treatment of Locally Advanced or Metastatic SDC
NCT ID:
NCT05898373
Condition:
Salivary Gland Cancer
Conditions: Official terms:
Salivary Gland Neoplasms
Antineoplastic Agents
Study type:
Interventional
Study phase:
Phase 1/Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
Randomized
Intervention model:
Crossover Assignment
Primary purpose:
Treatment
Masking:
Single (Investigator)
Intervention:
Intervention type:
Drug
Intervention name:
vedicitumomab (Edisil, RC48）
Description:
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 .
Arm group label:
vedicitumomab
Intervention type:
Drug
Intervention name:
vedicitumomab in combination with pyrrolizidine
Description:
vedicitumomab in combination with pyrrolizidine
Arm group label:
vedicitumomab in combination with pyrrolizidine
Intervention type:
Drug
Intervention name:
RC48 in combination with a platinum-based chemotherapeutic agent
Description:
RC48 in combination with a platinum-based chemotherapeutic agent
Arm group label:
RC48 in combination with a platinum-based chemotherapeutic agent
Intervention type:
Drug
Intervention name:
RC48 in combination with teraplizumab
Description:
RC48 in combination with teraplizumab
Arm group label:
RC48 in combination with teraplizumab
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.
Detailed description:
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.
Criteria for eligibility:
Criteria:
Inclusion Criteria:
(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%
Exclusion Criteria:
(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
Gender:
All
Minimum age:
18 Years
Maximum age:
N/A
Healthy volunteers:
No
Start date:
June 7, 2023
Completion date:
June 6, 2026
Lead sponsor:
Agency:
Peking Union Medical College
Agency class:
Other
Source:
Peking Union Medical College
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT05898373
