MRG003 Added to Ongoing Treatment After Progression in EGFR-Positive Advanced Thyroid Cancer

Ki vehet részt

• Aged 18 to 80 years, regardless of sex；
• Histologically or cytologically confirmed advanced anaplastic thyroid carcinoma (ATC) or poorly differentiated thyroid carcinoma (PDTC) for Cohort A, or radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC) for Cohort B；
• EGFR-positive tumor confirmed by immunohistochemistry (IHC)；
• Documented prior clinical benefit (complete response, partial response, or sustained stable disease) followed by RECIST 1.1 disease progression on the relevant ongoing regimen: lenvatinib plus an anti-PD-1 inhibitor for Cohort A, or lenvatinib for Cohort B. Continuing the prior regimen must remain clinically appropriate and tolerable. Cohort A must continue the same anti-PD-1 inhibitor；
• A minimum washout period of at least 4 weeks (or at least 5 half-lives, whichever is shorter) between the last dose of other chemotherapy/targeted therapy and the first MRG003 dose. This washout requirement does not apply to the ongoing lenvatinib in either cohort or the same ongoing anti-PD-1 inhibitor in Cohort A, which are continued as the study treatment backbone；
• Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1；
• Life expectancy ≥ 3 months；
• At least one measurable target lesion assessable by computed tomography (CT) or magnetic resonance imaging (MRI) according to RECIST 1.1. A new pretreatment imaging baseline must be obtained within 28 days before the first MRG003 dose；
• Laboratory test results meeting the following criteria: (1) Bone marrow function: hemoglobin (Hb) ≥ 90 g/L; white blood cell count (WBC) ≥ lower limit of normal (LLN); absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; platelet count ≥ 100 × 10⁹/L. (2) Renal function: serum creatinine (Cr) ≤ 1.5 × upper limit of normal (ULN); creatinine clearance rate (Ccr) ≥ 55 mL/min. (3) Liver function: total bilirubin ≤ 1.5 × ULN; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) ≤ 2.5 × ULN. (4) Coagulation function: international normalized ratio (INR) for prothrombin time ≤ 1.5 × ULN, and activated partial thromboplastin time (aPTT) within the normal range；
• Absence of severe complications, such as active gastrointestinal bleeding, perforation, jaundice, gastrointestinal obstruction, or non-neoplastic fever > 38°C；
• For female patients of childbearing potential: agreement to use contraception during the study period and for 6 months following study completion; a negative serum or urine pregnancy test within 7 days prior to study enrollment; and non-lactating status. For male patients: agreement to use contraception during the study period and for 6 months following study completion；
• Ability to understand the study protocol and voluntary provision of written informed consent；
• Patients are expected to have good compliance and be capable of adhering to the protocol for follow-up assessments of treatment efficacy and adverse events

Ki nem vehet részt

• Presence of symptomatic or untreated known brain metastases or other central nervous system (CNS) metastases. Completely resected and/or post-radiotherapy CNS metastases with documented stability or improvement are not exclusion criteria, provided that computed tomography (CT) demonstrates stability for at least 4 weeks prior to screening, with no evidence of cerebral edema and no requirement for glucocorticoids or anticonvulsants for management of CNS metastases；
• Prior treatment with an antibody-drug conjugate (ADC) with a monomethyl auristatin E (MMAE) payload；
• Subjects preparing to undergo or having previously undergone organ or bone marrow transplantation；
• Administration of a live vaccine within 30 days prior to the first dose of study treatment (injectable seasonal influenza vaccines are permitted, as they are inactivated vaccines)；
• Radiotherapy, chemotherapy, targeted therapy, or immunotherapy within 4 weeks before enrollment, except for the ongoing lenvatinib in both cohorts and the same ongoing anti-PD-1 inhibitor in Cohort A, which are intentionally continued as the study treatment backbone；
• Participation in another clinical trial of an investigational drug or device within 4 weeks before enrollment；
• Diagnosis of any other malignancy within the past 5 years, excluding cured in situ carcinoma and basal cell carcinoma；
• Subjects with psychiatric or neurological disorders who are unable to comply with the study protocol；
• Uncontrolled clinically significant cardiac symptoms or diseases, such as New York Heart Association (NYHA) Class III-IV heart failure, unstable angina pectoris, myocardial infarction within 6 months, or severe arrhythmia；
• Active infection (e.g., active hepatitis B virus [HBV], hepatitis C virus [HCV], or human immunodeficiency virus [HIV] infection) or active autoimmune disease requiring systemic therapy；
• History or evidence of interstitial lung disease or active non-infectious pneumonitis；
• Presence of other diseases rendering the subject unsuitable for enrollment, such as immunodeficiency, active pulmonary tuberculosis, hepatitis B (subjects are eligible for enrollment if HBV-DNA titer is <500 IU/mL following treatment and liver function is normal), positive hepatitis C virus test result, uncorrectable electrolyte disturbances, or uncontrolled pericardial, pleural, or peritoneal effusions；
• Known hypersensitivity to any component of the study drugs in this protocol；
• Pregnant or lactating women；
• Subjects deemed by the investigator to be unsuitable for enrollment