A Study of AL2846 Capsule Versus Placebo in the Treatment of Advanced Radioiodine-Refractory Differentiated Thyroid Carcinoma

Inclusion Criteria:

• Participants voluntarily join the study, sign the informed consent form, anddemonstrate good compliance.

• Histologically or cytologically confirmed locally advanced or metastaticdifferentiated thyroid carcinoma (DTC).

• Age: 18 years ≤ age <75 years (calculated based on the date of signing the informedconsent 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 ofEpidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy

• Confirmed iodine-refractory status, defined by one or more of the following:

1. Lesions show no iodine uptake on post-Iodine-131 therapy whole-body scan andare unlikely to benefit from further Iodine-131 therapy.

2. Previously iodine-avid lesions progressively lose iodine uptake afterIodine-131 therapy.

3. Mixed iodine-avid and non-iodine-avid lesions in the same patient with nobiochemical response.

4. Iodine-avid lesions with disease progression (radiologically confirmed) within 12 months.

5. 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:

1. Hemoglobin (HGB) ≥90 g/L.

2. Absolute neutrophil count (NEUT) ≥1.5×10⁹/L.

3. Platelet count (PLT) ≥90×10⁹/L.

4. Total bilirubin (TBIL) ≤1.5×ULN.

5. Alanine aminotransferase (ALT) and Aspartate transferase (AST) ≤2.5×ULN.

6. Creatinine clearance (CCR) ≥50 mL/min.

7. Prothrombin time (PT), Activated partial thromboplastin time (APTT), andInternational Normalized Ratio (INR) ≤1.5×ULN (without anticoagulationtherapy).

8. Serum albumin (ALB) ≥30 g/L (no albumin infusion within 7 days prior toscreening).

• For participants of childbearing potential: Agreement to use effective contraceptionduring the study and for 6 months after study completion. Females must have anegative serum/urine pregnancy test within 7 days before enrollment; males mustagree 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 twosituations are eligible for enrollment: other malignancies treated with a singlesurgery and achieving a disease - free survival (DFS) of 5 consecutive years; curedcervical carcinoma in situ, non - melanoma skin cancer, and superficial bladdertumors [Ta (non - invasive tumor), Tis (carcinoma in situ), and T1 (tumor invadingthe basement membrane)].

• Those with multiple factors affecting oral medications (such as difficulty inswallowing, chronic diarrhea, and intestinal obstruction, etc.);

• Adverse reactions from previous treatments have not recovered to a CommonTerminology Criteria for Adverse Events (CTCAE) Version 5.0. grade score ≤ 1, exceptfor grade 2 alopecia, grade 2 peripheral neuropathy, grade 2 anemia, non -clinically significant and asymptomatic grade 2 laboratory abnormalities, andhypothyroidism stabilized by hormone replacement therapy, and other toxicitiesjudged 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 drugswithin 4 weeks before randomization.

• As judged by the investigator, there are situations that seriously endanger thesafety of the subject or affect the subject's completion of the study.