Becotatug Vedotin (MRG003)

This study will evaluate whether adding MRG003 to an ongoing treatment regimen can produce confirmed tumor shrinkage in patients with EGFR-positive advanced thyroid cancer whose cancer initially benefited from that regimen and later progressed. The study will also evaluate the safety of the combinations. Cohort A will include patients with anaplastic or poorly differentiated thyroid carcinoma who previously benefited from lenvatinib plus an anti-PD-1 inhibitor and subsequently progressed. They will continue lenvatinib and the same anti-PD-1 inhibitor, with MRG003 added. Cohort B will include patients with radioactive iodine-refractory differentiated thyroid carcinoma who previously benefited from lenvatinib and subsequently progressed. They will continue lenvatinib, with MRG003 added. MRG003 will be given intravenously at 2.0 mg/kg every 3 weeks. The study plans to enroll 39 participants: 24 in Cohort A and 15 in Cohort B. The first 3 participants in each cohort will undergo an initial 6-week safety assessment before further enrollment is allowed. If additional safety assessment is needed, up to 6 participants who can be evaluated for dose-limiting toxicity will be assessed within the planned cohort enrollment. The main outcome is the proportion of patients in each cohort whose tumors shrink or disappear within 12 weeks after MRG003 starts, with the response confirmed at least 4 weeks later and by Week 18. Scans obtained before MRG003 is added provide the new baseline. Disease control is assessed at Week 12. Other response and survival outcomes are followed for up to 12 months after MRG003 starts. Safety follow-up continues during study treatment and for 90 days after the last study treatment dose, with longer follow-up of unresolved events as needed.