Sacituzumab tirumotecan with or without tislelizumab for advanced thyroid cancer

A Multicenter, Multi-Cohort, Phase II Study of Sacituzumab Tirumotecan With or Without Tislelizumab in Patients With Advanced Thyroid Cancer

This trial tests sacituzumab tirumotecan, given alone or together with the immunotherapy tislelizumab, in adults with unresectable or metastatic anaplastic, poorly differentiated, or radioactive iodine‑refractory differentiated thyroid cancer to see if it slows disease or improves survival.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 94 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Zhejiang Provincial People's Hospital (Academic / other)
• Drugs / interventions: Chemotherapy, immunotherapy, prednisone, sacituzumab, tislelizumab
• Locations: 1 site (Hangzhou, Zhejiang)
• Trial ID: NCT07068542 on ClinicalTrials.gov

What this trial studies

This is an open‑label, multi‑cohort Phase II exploratory trial enrolling adults with unresectable, locally advanced, or metastatic anaplastic thyroid carcinoma (ATC), poorly differentiated thyroid carcinoma (PDTC), or radioactive iodine‑refractory differentiated thyroid cancer (RAIR‑DTC). Patients with ATC receive sacituzumab tirumotecan combined with the PD‑1 inhibitor tislelizumab, while PDTC and RAIR‑DTC cohorts receive sacituzumab tirumotecan monotherapy. The ATC cohort uses overall survival (OS) as the primary endpoint, and the PDTC and RAIR‑DTC cohorts use investigator‑assessed progression‑free survival (PFS) per RECIST v1.1. Safety and tolerability are monitored throughout treatment and follow‑up.

Who should consider this trial

Good fit: Adults (≥18) with histologically confirmed unresectable, locally advanced, or metastatic ATC, PDTC, or RAIR‑DTC who meet the specified molecular and prior‑therapy criteria are eligible.

Not a fit: Patients who still have effective, approved targeted options for actionable mutations and have not tried those therapies, those with very poor performance status, or those unable to attend the study site are unlikely to benefit from participation.

Why it matters

Potential benefit: If effective, the regimen could prolong survival or delay disease progression for patients with advanced thyroid cancers that have limited treatment options.

How similar studies have performed: Antibody–drug conjugates targeting TROP2 and combinations of ADCs with PD‑1 inhibitors have shown activity in other solid tumors, but this particular sacituzumab tirumotecan ± tislelizumab approach in advanced thyroid cancer is relatively novel with limited prior data.

Eligibility criteria

Inclusion Criteria

Participants must meet all of the following criteria:

1\. Age ≥ 18 years at the time of informed consent. 2. Histologically confirmed unresectable, locally advanced, or metastatic:

* Anaplastic thyroid carcinoma (ATC), or
* Poorly differentiated thyroid carcinoma (PDTC), or
* Radioactive iodine-refractory differentiated thyroid carcinoma (RAIR-DTC), including papillary thyroid carcinoma or follicular thyroid carcinoma and variants.

  3\. For ATC or PDTC:
* No BRAF V600E mutation, RET fusion, NTRK fusion, or ALK fusion;
* Or harboring such alterations but have failed prior standard first-line targeted therapy.

  4\. For RAIR-DTC: Disease must be refractory to radioactive iodine (RAI), defined as at least one of the following:
* No RAI uptake in measurable lesions;
* Radiographic progression within 12 months after RAI therapy;
* Cumulative RAI dose \>600 mCi (or iodine-equivalent);
* Fluorodeoxyglucose (FDG)-avid measurable disease;
* Failure of prior multi-target tyrosine kinase inhibitor (TKI) therapy. 5. At least one measurable lesion per RECIST version 1.1. 6. ECOG performance status 0-2. 7. Life expectancy ≥ 12 weeks. 8. Adequate hematologic function:
* Absolute neutrophil count ≥ 1.2 × 10⁹/L
* Platelet count ≥ 100 × 10⁹/L
* Hemoglobin ≥ 90 g/L 9. Adequate hepatic function:
* AST and ALT ≤ 2.5 × upper limit of normal (ULN)
* ≤ 5 × ULN if liver metastases present
* Total bilirubin ≤ 1.5 × ULN 10. Adequate renal function:
* Creatinine clearance ≥ 60 mL/min (Cockcroft-Gault formula)

  1. No active autoimmune disease requiring systemic therapy.
  2. No concurrent active malignancy requiring treatment.
  3. Willing and able to provide written informed consent.

Exclusion Criteria

Participants meeting any of the following criteria will be excluded:

1. Prior therapy targeting TROP2.
2. Prior treatment with any topoisomerase I inhibitor antibody-drug conjugate.
3. Prior immune checkpoint agonists (e.g., ICOS, CD40, CD137, GITR, OX40) or immune cell therapy.
4. Another malignancy within 3 years prior to first dose, except adequately treated localized cancers (e.g., basal cell carcinoma, squamous cell carcinoma of the skin, carcinoma in situ of the cervix).
5. Uncontrolled or symptomatic central nervous system metastases.

   * Patients with treated and stable CNS disease for ≥4 weeks and off corticosteroids for ≥2 weeks may be eligible.
6. Significant uncontrolled comorbidities including, but not limited to:

   * Uncontrolled hypertension
   * Severe diabetes mellitus
   * Active infection
7. History of interstitial lung disease (ILD) or non-infectious pneumonitis requiring steroids, or current suspected ILD.
8. Unresolved toxicities from prior anti-cancer therapy greater than Grade 1 (CTCAE v5.0), except alopecia or other clinically insignificant toxicities.
9. Active autoimmune disease requiring systemic treatment within the past 2 years (excluding hormone replacement therapy such as levothyroxine or physiologic corticosteroids).
10. Systemic corticosteroid use \>10 mg/day prednisone equivalent within 10 days prior to first dose (except inhaled, topical, or physiologic replacement doses).
11. Known HIV infection or AIDS. Active syphilis infection.
12. History of allogeneic organ transplantation or hematopoietic stem cell transplantation.
13. Known severe hypersensitivity to study drugs or components.
14. Chemotherapy, radiotherapy, immunotherapy, biologic therapy, TKI, or systemic immune stimulation within protocol-defined washout period prior to first dose.
15. Pregnant or breastfeeding women.
16. Severe ocular disorders that may interfere with corneal healing (e.g., severe dry eye syndrome, severe meibomian gland disease).

Where this trial is running

Hangzhou, Zhejiang

• Zhejiang Provincial People's Hospital — Hangzhou, Zhejiang, China (Recruiting)

Study contacts

• Principal investigator: Minghua Ge — Zhejiang Provincial People's Hospital
• Study coordinator: Kexin Meng

Conditions Advanced Thyroid Carcinoma; Radioiodine-refractory Differentiated Thyroid Cancer; Poorly Differentiated Thyroid Carcinoma; radioiodine-refractory differentiated thyroid cancer; Sacituzumab tirumotecan; immunotherapy; TROP2; anaplastic thyroid carcinoma