Overview
This study aims to demonstrate that, in subjects with locally advanced or metastatic iodine - refractory differentiated thyroid cancer who have failed previous VEGFR - targeted therapy, AL2846 can significantly prolong progression - free survival (PFS) compared with placebo.
Eligibility
Inclusion Criteria:
- Participants voluntarily join the study, sign the informed consent form, and demonstrate good compliance.
- Histologically or cytologically confirmed locally advanced or metastatic differentiated thyroid carcinoma (DTC).
- Age: 18 years ≤ age <75 years (calculated based on the date of signing the informed consent form).
- Eastern Cooperative Oncology Group (ECOG) performance status score: 0-1.
- Anticipated survival >12 weeks.
- At least one measurable lesion confirmed by RECIST 1.1 criteria.
- Disease progression (per RECIST 1.1) after receiving **1 or 2 prior lines of Epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy
- Confirmed iodine-refractory status, defined by **one or more** of the following:
- Lesions show no iodine uptake on post-Iodine-131 therapy whole-body scan and are unlikely to benefit from further Iodine-131 therapy.
- Previously iodine-avid lesions progressively lose iodine uptake after Iodine-131 therapy.
- Mixed iodine-avid and non-iodine-avid lesions in the same patient with no biochemical response.
- Iodine-avid lesions with disease progression (radiologically confirmed) within 12 months.
- Cumulative Iodine-131 dose ≥600 mCi (22 GBq) with no disease response (radiologically confirmed).
- Thyroid stimulating hormone (TSH) ≤0.5 mIU/L under TSH-suppressive therapy.
- Laboratory parameters meeting the following criteria:
- Hemoglobin (HGB) ≥90 g/L.
- Absolute neutrophil count (NEUT) ≥1.5×10⁹/L.
- Platelet count (PLT) ≥90×10⁹/L.
- Total bilirubin (TBIL) ≤1.5×ULN.
- Alanine aminotransferase (ALT) and Aspartate transferase (AST) ≤2.5×ULN.
- Creatinine clearance (CCR) ≥50 mL/min.
- Prothrombin time (PT), Activated partial thromboplastin time (APTT), and International Normalized Ratio (INR) ≤1.5×ULN (without anticoagulation therapy).
- Serum albumin (ALB) ≥30 g/L (no albumin infusion within 7 days prior to screening).
- For participants of childbearing potential: Agreement to use effective contraception
during the study and for 6 months after study completion. Females must have a negative serum/urine pregnancy test within 7 days before enrollment; males must agree to effective contraception during and for 6 months post-study.
Exclusion Criteria:
- Patients with undifferentiated thyroid carcinoma or medullary thyroid carcinoma;
- Patients who have had or currently have other malignancies. The following two situations are eligible for enrollment: other malignancies treated with a single surgery and achieving a disease - free survival (DFS) of 5 consecutive years; cured cervical carcinoma in situ, non - melanoma skin cancer, and superficial bladder tumors [Ta (non - invasive tumor), Tis (carcinoma in situ), and T1 (tumor invading the basement membrane)].
- Those with multiple factors affecting oral medications (such as difficulty in swallowing, chronic diarrhea, and intestinal obstruction, etc.);
- Adverse reactions from previous treatments have not recovered to a Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0. grade score ≤ 1, except for grade 2 alopecia, grade 2 peripheral neuropathy, grade 2 anemia, non - clinically significant and asymptomatic grade 2 laboratory abnormalities, and hypothyroidism stabilized by hormone replacement therapy, and other toxicities judged by the investigator to have no safety risks.
- Known allergy to the excipient components of the study drug.
- Subjects who have participated in and used other anti - tumor clinical trial drugs within 4 weeks before randomization.
- As judged by the investigator, there are situations that seriously endanger the safety of the subject or affect the subject's completion of the study.