Anlotinib: 12 mg orally once daily; 2 weeks on / 1 week off, ≤4 cycles (alternative)
Pembrolizumab: 200 mg IV infusion every 3 weeks; ≤4 cycles
Sintilimab: 200 mg IV infusion every 3 weeks; ≤4 cycles
Cabozantinib: Cabozantinib 60 mg orally once daily, continuous 28-day cycles.
Bemosuzumab: China PD-L1 antibody bemosuzumab 900 mg IV every 2 weeks (14-day cycle).
Conversion Surgery: Conversion Surgery if resectable
Study summary
This multicenter registry tests whether genomically matched neoadjuvant therapy (1-4 cycles tailored to BRAF V600E, RET fusion/mutation, isolated TERT mutation, triple-negative BRAF/RET/TERT, or ICI ± TKI) can render locally advanced, initially unresectable-or high-morbidity-thyroid cancers operable. The primary endpoint is conversion-to-surgery; key secondaries are R0/1 margin rate and 12-month event-free survival, with propensity-score weighting correcting cohort imbalances. Findings aim to define a precision-guided neoadjuvant standard for down-staging advanced thyroid tumors.
Eligibility
Sex
ALL
Min age
18 Years
Max age
80 Years
Healthy volunteers
No
Inclusion Criteria:
1. Age ≥ 18 years at enrollment.
2. Histologically or cytologically confirmed thyroid carcinoma that meets ≥ 1 of the following:
* Radioactive-iodine-refractory differentiated thyroid carcinoma (DTC)
* Medullary thyroid carcinoma (MTC)
* Anaplastic or poorly differentiated thyroid carcinoma (ATC/PDTC)
* Other locally advanced / metastatic thyroid malignancy deemed incurable by surgery alone.
3. Disease judged unresectable or entailing prohibitively high-morbidity surgery at baseline by a multidisciplinary thyroid-oncology board.
4. Documented molecular or immunophenotype qualifying for ≥ 1 study arm:
* BRAF V600E mutation
* RET gene fusion
* RET activating point mutation (e.g., M918T)
* NTRK1/2/3 fusion
* Isolated TERT-promoter mutation with no BRAF/RET/NTRK alterations
* Driver-negative / VEGFR-wild type ("triple-negative")
* PD-L1 expression ≥ 1 % OR progression after prior multi-kinase inhibitor (MKI).
5. ECOG Performance Status 0-2.
6. At least one measurable lesion per RECIST v1.1 / iRECIST (MTC with calcitonin/CEA evaluable disease accepted).
7. Written informed consent obtained.
Exclusion Criteria:
1. Untreated or symptomatic CNS metastases; patients with treated, stable lesions ≥ 4 weeks and off corticosteroids are eligible.
2. Pregnant or breastfeeding. Women and men of child-bearing potential must agree to effective contraception during study and for ≥ 120 days after last dose (≥ 180 days for men after dabrafenib/trametinib).
Primary outcome measure(s)
Real-World Progression-Free Survival (rwPFS) — Baseline to radiologic/clinical progression or death, whichever occurs first, up to 36 months Time from Cycle 1 Day 1 to the earliest date of disease progression (RECIST/iRECIST) or all-cause death.
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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