Adenoid Cystic Carcinoma of the Head and Neck, SBRT, Antibody-drug Conjugates
Conditions
Brief summary
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.
Interventions
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.
RADIATIONSBRT
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.
DRUGBecotatug Vedotin or Sacituzumab Tirumotecan
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.
Sponsors
Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
1. Provide written informed consent prior to the initiation of any study-specific procedures. 2. Male or female patients aged 18-80 years. 3. Histologically or cytologically confirmed head and neck squamous cell carcinoma or adenoid cystic carcinoma, expressing ADC-related targets (e.g., EGFR, TROP2), with evidence of recurrence and/or metastasis. 4. Patients must have experienced disease progression after first-line standard therapy or be deemed unsuitable for such therapy, and meet the following conditions: (1) For adenoid cystic carcinoma, first-line treatment should include anti-angiogenic agents (e.g., TKIs or monoclonal antibodies), chemotherapy, or patients are considered unsuitable for standard first-line therapy by the investigator (e.g., high bleeding risk, non-healing wounds); (2) For other salivary gland carcinomas, patients must have progressed after first-line standard therapy or be unsuitable for such therapy. 5. At least one measurable lesion according to RECIST version 1.1 based on imaging. 6. Life expectancy of at least 6 months. 7. ECOG performance status (PS) score of 0-1. 8. Adequate organ function, defined by the following laboratory criteria: (1) Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L without use of granulocyte colony-stimulating factor within 14 days prior to testing; (2) Platelet count ≥ 90 × 10⁹/L without transfusion within 14 days prior to testing; (3) Hemoglobin \> 9 g/dL without transfusion or erythropoietin use within 14 days prior to testing; (4) Total bilirubin ≤ 1.5 × upper limit of normal (ULN); (5) Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤ 2.5 × ULN; (6) Serum creatinine ≤ 1.5 × ULN and creatinine clearance ≥ 60 mL/min (calculated using the Cockcroft-Gault formula); (7) Adequate coagulation function, defined as international normalized ratio (INR) or prothrombin time (PT) ≤ 1.5 × ULN; (8) Normal thyroid function, defined as thyroid-stimulating hormone (TSH) within the normal range. Patients with abnormal baseline TSH may still be eligible if total T3 (or FT3) and FT4 are within normal limits; (9) Myocardial enzyme levels within the normal range (isolated laboratory abnormalities deemed clinically insignificant by the investigator are acceptable); (10) Women of childbearing potential must have a negative urine or serum pregnancy test within 3 days prior to the first dose (Cycle 1 Day 1). If a urine test result is inconclusive, a serum test is required. Women of non-childbearing potential are defined as those who are postmenopausal for at least 1 year, or who have undergone surgical sterilization or hysterectomy; (11) Willingness and ability to comply with study procedures, including treatment, contraceptive measures, scheduled visits, and follow-up assessments.
Exclusion criteria
1. Diagnosis of malignancies other than head and neck tumors within 5 years prior to the first dose (except for adequately treated basal cell carcinoma of the skin, squamous cell carcinoma of the skin, and/or carcinoma in situ following curative resection). 2. Participation in another interventional clinical study or receipt of investigational drugs/devices within 4 weeks prior to the first dose. 3. Prior treatment with ADC agents. 4. Treatment of traditional Chinese medicines with antitumor indications or immunomodulatory agents (e.g., thymosin, interferon, interleukins; except for local use for pleural effusion control) within 2 weeks prior to the first dose. 5. Known hypersensitivity to the active ingredients or excipients of the study drug. 6. Failure to recover from toxicities and/or complications caused by prior interventions to ≤ Grade 1 or baseline (excluding fatigue or alopecia) prior to treatment initiation. 7. Known history of human immunodeficiency virus (HIV) infection (i.e., HIV-1/2 antibody positive). 8. Untreated active hepatitis B infection (defined as HBsAg positive with HBV-DNA levels above the upper limit of normal for the study center laboratory). Note: Patients with hepatitis B may still be eligible if: (1) HBV viral load \< 2.5 × 10³ copies/mL (500 IU/mL) prior to first dosing, and patients receive anti-HBV therapy throughout the study; (2) Patients with anti-HBc (+), HBsAg (-), anti-HBs (-), and negative HBV viral load do not require prophylactic anti-HBV therapy but must be closely monitored for viral reactivation. 9. Active hepatitis C infection (HCV antibody positive with HCV-RNA above the lower limit of detection). 10. Pregnant or breastfeeding women. 11. Presence of any severe or uncontrolled systemic disease, including but not limited to: (1) Significant and symptomatic abnormalities in cardiac rhythm, conduction, or morphology on resting ECG that are difficult to control, such as complete left bundle branch block, second-degree or higher atrioventricular block, ventricular arrhythmias, or atrial fibrillation; (2) Unstable angina, congestive heart failure, or chronic heart failure with New York Heart Association (NYHA) class ≥ II; (3) Any arterial thrombosis, embolism, or ischemic event within 6 months prior to enrollment (e.g., myocardial infarction, unstable angina, cerebrovascular accident, transient ischemic attack); (4) Major surgery (e.g., craniotomy, thoracotomy, laparotomy) within 4 weeks prior to the first dose, or presence of unhealed wounds, ulcers, or fractures. Tissue biopsy or minor surgical procedures within 7 days prior to first dosing are also exclusionary, except for venous catheter placement for infusion; (5) Poorly controlled hypertension (systolic \>140 mmHg and/or diastolic \>90 mmHg); (6) Active pulmonary tuberculosis; (7) Active or uncontrolled infections requiring systemic therapy; (8) Clinically active diverticulitis, abdominal abscess, or gastrointestinal obstruction; (9) Liver diseases such as cirrhosis, decompensated liver disease, or acute/chronic active hepatitis; (10) Poorly controlled diabetes mellitus (fasting blood glucose \>10 mmol/L); (11) Proteinuria ≥ ++ on urinalysis confirmed by 24-hour urinary protein \>1.0 g; (12) Psychiatric disorders that interfere with treatment compliance; (13) Any medical history, disease condition, treatment, or laboratory abnormality that may interfere with study results or the patient's full participation, or any other condition deemed unsuitable for enrollment by the investigator.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | 1-year | 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Response (TTR) | 1-year | 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. |
| Disease Disease Control Rate (DCR) | 1-year | 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). |
| Progression-Free Survival (PFS) | 1-year | Time from first treatment to disease progression or death from any cause, whichever occurs first. |
| Overall Survival (OS) | 1-year | Time from first treatment to death from any cause. |
| Duration of Response (DOR) | 1-year | Time from first documented objective response to disease progression or death, in patients with a confirmed objective response. |
| Adverse Events (AEs) | 2-year | Including type, incidence, severity (graded per NCI-CTCAE v5.0), duration, and relationship to study drugs. |
Outcome results
None listed