A Phase 2 interventional study of Becotatug Vedotin (MRG003) and Lenvatinib in Thyroid Cancer, Tumor and Advanced Thyroid Carcinoma, sponsored by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University. Recruiting at 1 site in China. Open to participants aged 18 Years to 80 Years. Per ClinicalTrials.gov, last updated 2026-10-14.
Sponsored by Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University · Phase 2, Interventional, and Treatment
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.
This prospective, open-label, single-center, nonrandomized phase II study will investigate MRG003 as an add-on treatment after RECIST 1.1 disease progression on a previously beneficial treatment regimen. Eligible participants must have EGFR-positive tumors by immunohistochemistry and documented prior clinical benefit consisting of complete response, partial response, or sustained stable disease, followed by radiographic progression. Continued use of the prior regimen must remain clinically appropriate and tolerable.
Cohort A includes anaplastic or poorly differentiated thyroid carcinoma after prior benefit from lenvatinib plus an anti-PD-1 inhibitor and subsequent progression. Lenvatinib and the same anti-PD-1 inhibitor will be continued, and MRG003 will be added. Cohort B includes radioactive iodine-refractory differentiated thyroid carcinoma after prior benefit from lenvatinib and subsequent progression. Lenvatinib will be continued, and MRG003 will be added.
MRG003 is the only newly introduced anticancer agent in both cohorts and will be administered intravenously at 2.0 mg/kg every 3 weeks. Lenvatinib will be continued at the tolerated dose used at progression; in Cohort A, the same anti-PD-1 inhibitor will continue according to the prior regimen. Dose interruptions, modifications, and discontinuation will follow protocol-defined safety rules. Add-on treatment will continue until subsequent disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion.
This is an exploratory phase II study with planned enrollment of 39 participants: 24 in Cohort A and 15 in Cohort B. The cohort allocation reflects anticipated recruitment feasibility. Each cohort includes its initial safety lead-in participants. Early confirmed objective response rate will be summarized separately for each cohort using response counts, full-analysis-set denominators, percentages, and two-sided exact 95% Clopper-Pearson confidence intervals. The full analysis set includes enrolled participants who receive at least one dose of MRG003. Participants without a qualifying confirmed response are counted as nonresponders. The study is not designed to provide separately powered efficacy hypothesis tests for both cohorts.
Each cohort begins with 3 participants in a fixed-starting-dose safety lead-in. The primary dose-limiting toxicity (DLT) assessment window is Days 1-42 after the first MRG003 dose, covering two 21-day cycles. The first participant in each cohort must complete the first 21-day cycle and undergo safety review before the second participant starts; the third starts at least 7 days after the second. The first participants in the two cohorts are also staggered by at least 7 days.
If 0 of 3 DLT-evaluable participants experience a DLT and there are no other unresolved safety concerns, cohort expansion may proceed after documented safety review. One suspected DLT triggers immediate suspension of cohort enrollment and study dosing pending review; if the event is manageable and no major safety signal is present, the lead-in may expand to 6 DLT-evaluable participants within the planned cohort enrollment. Expansion requires no more than 1 of 6 evaluable participants to experience a DLT and a favorable safety review. DLTs in 2 or more participants during the cohort safety lead-in stop expansion of the current cohort regimen and trigger suspension of relevant study dosing pending review. Multiple DLT events in one participant count as one participant for these boundaries. A potentially treatment-related or unexplained death, life-threatening event, or another prespecified major safety signal triggers immediate study-wide suspension of enrollment and study dosing pending urgent review. Necessary medical care and individual risk assessment continue during a suspension. Safety monitoring continues beyond the DLT window.
Participants who receive MRG003 remain in the full analysis and safety sets regardless of toxicity, early discontinuation, or incomplete DLT assessment. Any participants enrolled to complete the DLT-evaluable lead-in are counted within the planned cohort and total enrollment. DLT assessment is based on new or worsened CTCAE v5.0 toxicities with a reasonable possibility of relationship to any component of the study regimen or their interaction.
A new tumor imaging baseline will be obtained within 28 days before the first MRG003 dose. Tumor assessments will be performed at Week 6 and every 6 weeks thereafter within the 12-month efficacy observation period, until progression or an applicable censoring condition. Necessary imaging follow-up continues after treatment discontinuation without progression. Complete and partial responses must be confirmed by a subsequent assessment at least 4 weeks later. Unscheduled imaging may be performed for suspected progression.
The primary outcome is early confirmed objective response rate according to RECIST 1.1, evaluated separately in each cohort: CR or PR must first be documented within 12 weeks after the first MRG003 dose and confirmed at least 4 weeks later, no later than Week 18. Both the initial response and confirmation must precede progression or new anticancer therapy. Responses first documented after Week 12 do not contribute to the primary outcome. Scheduled assessments at Weeks 6, 12, and 18 support this endpoint. Participants without a response meeting these requirements are counted as nonresponders in the full analysis set.
Disease control rate is the proportion of each cohort with CR, PR, or stable disease at the Week 12 assessment. It describes status at that time point, rather than best overall disease control over a period. Subsequent confirmation of CR or PR is not required for this measure. Progression, death, or new anticancer therapy before the Week 12 assessment, or absence of an adequate Week 12 assessment, is counted as no disease control.
Time to response and duration of response are evaluated among participants whose initial response and confirmation both occur within 12 months after the first MRG003 dose, before progression or new anticancer therapy. Eligible late responders beyond Week 12 may contribute to these secondary analyses. Time to response ends at the initial response date; duration of response starts on that date and ends at subsequent progression or death. Duration-of-response follow-up ends 12 months after the first MRG003 dose, not 12 months after the response.
Progression-free survival is measured from the first MRG003 dose to subsequent RECIST 1.1 progression or death, whichever occurs first, with follow-up capped at 12 months after the first MRG003 dose. Progression establishing eligibility is not an event for this outcome. For progression-free survival and duration of response, participants without an event are censored at the last adequate tumor assessment within the observation window; if new anticancer therapy begins first, censoring is at the last adequate assessment before that therapy.
Overall survival is measured from the first MRG003 dose to death from any cause, through 12 months after that dose, with censoring at the last date known alive within this window. Survival follow-up continues after progression or new anticancer therapy, every 12 weeks after treatment discontinuation, with a planned 12-month status assessment. Analyses are performed separately by cohort; 12-month survival and Kaplan-Meier estimates are reported, and median overall survival is reported only if estimable. Completion of the early primary endpoint does not end the remaining efficacy or safety follow-up. Safety is assessed during each treatment cycle and follows the separate collection rules below.
All adverse events (AEs), including serious adverse events (SAEs), are collected from informed consent, throughout study treatment, and through 90 days after the last dose of any protocol-defined study treatment, irrespective of attribution. The reference date is the latest administration date across all components administered within the study treatment regimen. Pre-existing conditions are recorded at baseline; treatment-emergent AEs are new or worsened events after the first MRG003 dose. Events are coded using MedDRA and graded using NCI CTCAE v5.0, and AEs and SAEs are summarized by cohort. The date of discontinuation of study treatment and any transition to routine care are documented; subsequent routine-care treatment does not reset the 90-day window.
Unresolved AEs and SAEs are followed until resolution, return to baseline, or medical stabilization with the subsequent care plan documented. Suspected treatment-related SAEs learned of after the 90-day window continue to be evaluated, recorded, and reported under the applicable safety reporting procedures. Initiation of other anticancer therapy does not automatically end safety follow-up; subsequent treatments and event attribution are documented. This safety follow-up is separate from the 42-day DLT assessment and the efficacy outcome assessment windows.
819 studies on the registry are indexed under Thyroid Neoplasms; 216 are open to participants now.
This study's planned enrollment of 39 is below the median of 50 across 518 interventional studies indexed under Thyroid Neoplasms.
Browse Thyroid Neoplasms studies →Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University is the lead sponsor of 477 studies on the registry; 278 are open to participants now.
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Exclusion Criteria:
Participants with EGFR-positive anaplastic or poorly differentiated thyroid carcinoma must have achieved complete response, partial response, or sustained stable disease with lenvatinib plus an anti-PD-1 inhibitor, followed by RECIST 1.1 progression. Lenvatinib continues at the tolerated dose used at progression, with the same anti-PD-1 inhibitor according to the prior regimen. MRG003 is added at 2.0 mg/kg intravenously every 3 weeks. Dose modifications follow protocol-defined safety rules. Treatment continues until subsequent progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion. Planned enrollment is 24, including 3 initial safety lead-in participants. DLT assessment covers Days 1-42 after the first MRG003 dose. If required by safety review, the lead-in may expand to 6 DLT-evaluable participants within the planned 24. Expansion requires the prespecified safety review and stopping rules.
Drug: Becotatug Vedotin (MRG003) · Drug: Lenvatinib · Biological: Anti-PD-1 Inhibitor (Continuation of Prior Treatment)
Participants with EGFR-positive radioactive iodine-refractory differentiated thyroid carcinoma must have achieved complete response, partial response, or sustained stable disease with lenvatinib, followed by RECIST 1.1 progression. Lenvatinib continues at the tolerated dose used at progression. MRG003 is added at 2.0 mg/kg intravenously every 3 weeks. Dose modifications follow protocol-defined safety rules. Treatment continues until subsequent progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion. Planned enrollment is 15, including 3 initial safety lead-in participants. DLT assessment covers Days 1-42 after the first MRG003 dose. If required by safety review, the lead-in may expand to 6 DLT-evaluable participants within the planned 15. Expansion requires the prespecified safety review and stopping rules.
Drug: Becotatug Vedotin (MRG003) · Drug: Lenvatinib
MRG003 is added at 2.0 mg/kg intravenously on Day 1 of each 3-week cycle to the ongoing treatment backbone: lenvatinib plus the same anti-PD-1 inhibitor in Cohort A, or lenvatinib in Cohort B. MRG003 continues until subsequent disease progression, unacceptable toxicity, withdrawal of consent, or another protocol-defined discontinuation criterion; dose modifications follow protocol-defined safety rules. Infusion is over 60 +/- 15 minutes, with the first infusion lasting at least 60 minutes. Participants are monitored for infusion-related reactions during infusion and for at least 60 minutes afterward (at least 120 minutes after the first dose).
Continued orally once daily in both cohorts at the tolerated dose used at progression before MRG003 addition. This is continuation of the prior treatment backbone, with protocol-defined dose interruptions, reductions, or discontinuation for safety. MRG003 is added after documented prior clinical benefit and subsequent RECIST 1.1 progression.
Cohort A only: continue the same anti-PD-1 inhibitor used with lenvatinib when prior clinical benefit and subsequent RECIST 1.1 progression occurred. The agent, dose, route, and dosing schedule follow the participant's prior regimen, with protocol-defined safety adjustments. A different anti-PD-1 inhibitor is not introduced as part of the add-on intervention. MRG003 is the only newly added anticancer agent.
Early Confirmed Objective Response Rate Within 12 Weeks After Addition of MRG003
The percentage of participants in each cohort with a complete response (CR) or partial response (PR) first documented within 12 weeks after the first MRG003 dose and confirmed at least 4 weeks later, no later than Week 18, according to RECIST 1.1. Responses use the new imaging baseline obtained within 28 days before MRG003 addition. Assessments are scheduled at Weeks 6, 12, and 18. The full analysis set includes all enrolled participants who receive at least one MRG003 dose. Participants without a response meeting the timing and confirmation requirements are counted as nonresponders. Responses first documented after Week 12, or after progression or initiation of new anticancer therapy, do not contribute to this primary outcome. Qualifying confirmation must precede progression or new anticancer therapy.
Time frame: From the first MRG003 dose through Week 18; initial CR or PR must be documented within the first 12 weeks.
Overall Survival After Addition of MRG003
Time from the first MRG003 dose to death from any cause, evaluated separately by cohort, with observation through 12 months after the first MRG003 dose. Participants without documented death within this period are censored at the last date known alive within the observation window. Survival status continues to be collected after progression, discontinuation of study treatment, or initiation of new anticancer therapy, unless consent for follow-up is withdrawn or follow-up is otherwise unavailable. Survival follow-up is performed every 12 weeks after treatment discontinuation, with a planned 12-month survival status assessment. Kaplan-Meier estimates and 12-month survival probability are reported; median OS is reported only if estimable.
Time frame: From the first MRG003 dose to death from any cause, assessed for up to 12 months after the first MRG003 dose.
Time to Response After Addition of MRG003
Time from the first MRG003 dose to the first documented CR or PR that is subsequently confirmed at least 4 weeks later according to RECIST 1.1. Analyzed separately by cohort among participants whose response and confirmation both occur within 12 months after the first MRG003 dose, before progression or new anticancer therapy. The initial response date, not the confirmation date, is used. Responders first responding after Week 12 may be included in this secondary analysis but not in the early primary ORR. Participants without a qualifying confirmed response by the 12-month cutoff are not included in this responder-only TTR summary; their number is reported.
Time frame: From the first MRG003 dose through 12 months; both initial response and response confirmation must occur within this period.
Incidence of Adverse Events by Cohort
Counts and percentages of participants with adverse events (AEs) and serious adverse events (SAEs) will be reported by cohort, including the safety lead-in. All AEs/SAEs are collected from informed consent through treatment and 90 days after the last protocol-defined study drug dose, irrespective of attribution. Events are coded using MedDRA and graded by NCI CTCAE v5.0, with maximum grade and treatment relationship summarized. Pre-existing conditions are recorded at baseline; treatment-emergent AEs are new or worsened after the first MRG003 dose. Unresolved events are followed until resolution, return to baseline, or medical stabilization. Suspected treatment-related SAEs learned of after 90 days remain subject to evaluation, recording, and safety reporting. Starting other anticancer treatment does not end safety follow-up. Routine care after documented discontinuation of study treatment does not reset the 90-day clock.
Time frame: From informed consent, throughout study treatment, through 90 days after the last dose of any protocol-defined study treatment (latest dose date across components).
Disease Control Rate at Week 12 After Addition of MRG003
The percentage of participants in each cohort's full analysis set with CR, PR, or stable disease at the Week 12 RECIST 1.1 assessment, relative to the new pre-MRG003 imaging baseline. This is disease-control status at the specified time point, not best overall response over a period. Participants with progression, death, or initiation of new anticancer therapy before that assessment, or without an adequate Week 12 assessment, are counted as not achieving disease control. Subsequent confirmation of CR or PR is not required for this time-point disease-control measure; confirmation remains required for the primary ORR outcome.
Time frame: At Week 12 after the first MRG003 dose.
Progression-Free Survival After Addition of MRG003
Time from the first MRG003 dose to subsequent RECIST 1.1 disease progression or death from any cause, whichever occurs first, evaluated separately by cohort using the new pre-MRG003 baseline. The progression establishing study eligibility is not a PFS event. Follow-up for this outcome is capped at 12 months after the first MRG003 dose. Participants without an event are censored at their last adequate tumor assessment without progression within this period. If new anticancer therapy starts before a PFS event, censoring is at the last adequate assessment before that therapy. Tumor assessments occur every 6 weeks; necessary imaging follow-up continues after treatment discontinuation without progression, until a prespecified endpoint or censoring condition.
Time frame: From the first MRG003 dose until subsequent disease progression or death, whichever occurs first, assessed for up to 12 months after the first MRG003 dose.
Duration of Response After Addition of MRG003
Among participants whose CR or PR and its confirmation at least 4 weeks later both occur within 12 months after the first MRG003 dose and before progression or new anticancer therapy, time from the first response date to subsequent RECIST 1.1 progression or death, whichever occurs first. Evaluated separately by cohort, including eligible late responders beyond the early primary ORR window. The observation cutoff is 12 months after the first MRG003 dose, not 12 months after response. Event-free participants are censored at the last adequate tumor assessment within this period; if new anticancer therapy begins first, censor at the last adequate assessment before that therapy. The initial response date, not the confirmation date, starts DoR.
Time frame: From first CR or PR subsequently confirmed to progression or death, whichever occurs first, with follow-up ending 12 months after the first MRG003 dose.
Plan to share: Undecided
Started Sep 2026 (actual). Primary completion is estimated for Dec 2027, 15 months after the start.
Of 82 non-industry phase 2 interventional studies under Thyroid Neoplasms, half reached primary completion within 84 months of starting (the median), counting those still running; a quarter within 49 and three quarters within 122. This study's planned 15 months is below that.
Counting every sponsor, half of 96 studies reached it within 73 months; a quarter within 41 and three quarters within 119.
How these figures are worked out, and which studies are left out of them.
From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗
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