This is a single-arm, single-center, exploratory clinical study. The study plans to enroll patients with recurrent or metastatic head and neck salivary gland carcinoma (HN-SGC) . The trial comprises two cohorts: Cohort 1 (adenoid cystic carcinoma, ACC) and Cohort 2 (non-ACC SGC). Patients in Cohort 1 will initially receive MRG003, an EGFR-targeted antibody-drug conjugate (ADC). Patients in Cohort 2 will initially receive either MRG003 (EGFR-ADC) or a TROP2-targeted ADC. The selection between these two ADC therapies for Cohort 2 will be determined by the investigator based on the expression levels of specific tumor surface receptors. Tumor response will be assessed by imaging every 6 weeks (±7 days). Subjects who are assessed as having stable disease (SD) on two consecutive evaluations or who develop oligometastatic progression will receive stereotactic body radiation therapy (SBRT). Following SBRT, maintenance therapy with the original ADC will be continued. Treatment discontinuation will be permitted due to disease progression, death, intolerable toxicity, withdrawal of consent, initiation of new anti-tumor therapy, or other protocol-specified reasons, whichever occurs first. After treatment completion, all subjects will enter a post-treatment phase for safety visits and survival follow-up. For subjects who discontinue treatment for reasons other than disease progression or death, tumor progression follow-up will also be conducted during the post-treatment period.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
40
The initial dosage is 2.3 mg/kg, administered intravenously every three weeks per treatment cycle. A single dose reduction level (Level 1) to 2.0 mg/kg is permitted based on predefined criteria; the specific dose reduction scheme is detailed in the study protocol.
The specific SBRT dose and fractionation will be determined based on the lesion site and prior history of radiation therapy. The standard dose range for SBRT will be 14 Gy-36 Gy, administered over 4-6 fractions (for example, 3.7 Gy per fractionfor 4 fractions). Adjustments to the dose and fractionation schedule maybe made according to individual patient needs and prior treatments.
Becotatug Vedotin (MRG003): The initial dosage is 2.3 mg/kg, administered intravenously every three weeks per treatment cycle. A single dose reduction level (Level 1) to 2.0 mg/kg is permitted based on predefined criteria; the specific dose reduction scheme is detailed in the study protocol. Sacituzumab Tirumotecan (SKB264): The initial dosage is 5 mg/kg, administered intravenously every two weeks. A single dose reduction level (Level 1) to 4 mg/kg is permitted based on predefined criteria; the specific dose reduction scheme is detailed in the study protocol.
Objective Response Rate (ORR)
the proportion of patients with a reduction in tumor volume of a predefined amount and for a minimum time period, including complete response (CR) and partial response (PR) cases
Time frame: 1-year
Time to Response (TTR)
the interval from the date of treatmentinitiation (typically the first dose) to the date of the firstdocumented objective response (complete response \[CR\] or partial response \[PR\]). * TTR1 (Onset of response to ADC): Defined as the time from initiationof antibody-drug conjugate (ADC) therapy to the first occurrence of an objective response(PR or CR). This metric reflects the initial onset of action of the ADC, whether administeredas monotherapy or as part of a combination regimen. * TTR2(Onset of response to the overall combination therapy): Defined as the time from initiation of the fullcombination treatment regimen (i.e., after receivingADC therapy and completing the first course of SBRT) to the first occurrence of an objective response. This endpoint evaluates the onset of efficacy ofthe combination therapy as an integrated treatment approach.
Time frame: 1-year
Disease Disease Control Rate (DCR)
Proportion of patients with a best overall response of confirmed CR, PR, or SD (SD must be confirmed at least 4 weeks after initial documentation).
Time frame: 1-year
Progression-Free Survival (PFS)
Time from first treatment to disease progression or death from any cause, whichever occurs first.
Time frame: 1-year
Overall Survival (OS)
Time from first treatment to death from any cause.
Time frame: 1-year
Duration of Response (DOR)
Time from first documented objective response to disease progression or death, in patients with a confirmed objective response.
Time frame: 1-year
Adverse Events (AEs)
Including type, incidence, severity (graded per NCI-CTCAE v5.0), duration, and relationship to study drugs.
Time frame: 2-year
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