Sacituzumab Tirumotecan Combined With Immunotherapy in Advanced Thyroid Cancer

Official title

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

Overview

This is a multicenter, open-label, multi-cohort Phase II exploratory study designed to evaluate the efficacy and safety of sacituzumab tirumotecan with or without tislelizumab in patients 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 will receive sacituzumab tirumotecan in combination with tislelizumab. Patients with PDTC and RAIR-DTC will receive sacituzumab tirumotecan monotherapy. The primary objective in the ATC cohort is overall survival (OS). In the PDTC and RAIR-DTC cohorts, the primary objective is progression-free survival (PFS) assessed by investigators per RECIST v1.1.

Interventions

• Drug Sacituzumab Tirumotecan (SKB264) plus Tislelizumab
  Sacituzumab tirumotecan: 5mg/kg, IV, Q6W, D1, D15, D29 Tislelizumab: 200mg, IV, Q6W, D1, D15, D29
• Drug Sacituzumab Tirumotecan (SKB264)
  Sacituzumab tirumotecan: 5mg, IV, Q6W, D1, D15, D29

Primary outcome measures

• Overall Survival (OS) - ATC Cohort [Time frame: From first dose until death from any cause (up to approximately 24 months after enrollment)]
• Progression-Free Survival (PFS) - PDTC and RAIR-DTC Cohorts [Time frame: From first dose until documented disease progression or death (up to approximately 24 months)]

Secondary outcome measures (6)

• Progression-Free Survival (PFS) - ATC Cohort [Time frame: From first dose until documented disease progression or death (up to approximately 24 months)]
• Overall Survival (OS) - PDTC and RAIR-DTC Cohorts [Time frame: From first dose until death from any cause (up to approximately 24 months)]
• Objective Response Rate (ORR) [Time frame: Up to approximately 24 months]
• Disease Control Rate (DCR) [Time frame: Up to approximately 24 months]
• Duration of Response (DoR) [Time frame: Up to approximately 24 months]
• Incidence of Treatment-Emergent Adverse Events (TEAEs) [Time frame: From first dose until 30 days after last dose (SAEs up to 90 days)]

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)

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

Exclusion criteria

Participants meeting any of the following criteria will be excluded:

• Prior therapy targeting TROP2.
• Prior treatment with any topoisomerase I inhibitor antibody-drug conjugate.
• Prior immune checkpoint agonists (e.g., ICOS, CD40, CD137, GITR, OX40) or immune cell therapy.
• 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).
• 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.
• Significant uncontrolled comorbidities including, but not limited to:

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Zhejiang Provincial People's Hospital — Hangzhou

Identifiers

NCT: NCT07068542 · KY2025070

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗