NCT07522879

A Study of Becotatug Vedotin (MRG003) Combined With Epirubicin as Neoadjuvant Therapy for EGFR-Positive, Unresectable Recurrent Sinonasal Adenoid Cystic Carcinoma

Becotatug Vedotin (MRG003) Combined With Epirubicin as Neoadjuvant Therapy for EGFR-Positive, Unresectable Recurrent Sinonasal Adenoid Cystic Carcinoma: A Prospective, Multicenter Clinical Study

• Status: Not Yet Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 40 (estimated)
• Sponsor: Eye & ENT Hospital of Fudan University · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

Summary

This prospective, multicenter clinical study aims to evaluate the efficacy and safety of neoadjuvant therapy with MRG003 (Becotatug vedotin) combined with epirubicin in patients with EGFR-positive, unresectable recurrent sinonasal adenoid cystic carcinoma (SNACC). The primary question is whether this combination can achieve a sufficient objective response rate (ORR) to enable subsequent radical surgery or improve disease control.

Detailed description

This is a prospective, multicenter, single-arm, open-label phase II clinical study. Patients with histologically confirmed recurrent sinonasal adenoid cystic carcinoma (SNACC) that is deemed unresectable by a multidisciplinary team (MDT) and positive for EGFR expression (IHC) are eligible. Intervention: * MRG003 (Becotatug vedotin): 2.0 mg/kg IV on day 1 of each 21-day cycle. * Epirubicin: 75 mg/m² IV on day 1 of each 21-day cycle. * Total of 3 neoadjuvant cycles. Primary Outcome Measure: Objective response rate (ORR) according to RECIST v1.1, assessed 21 days (±7 days) after the third cycle. Secondary Outcome Measures: * Safety and tolerability (CTCAE v5.0) * Surgical conversion rate (proportion of patients achieving R0/R1 resection after neoadjuvant therapy) * R0 resection rate and pathological response rate (major pathological response ≤10% viable tumor cells; pathological complete response 0%) * Disease control rate (DCR), progression-free survival (PFS), and overall survival (OS) Sample Size: 40 evaluable patients. Assuming a historical ORR of 10% with single-agent epirubicin, the study is designed to detect an improvement to 35% with the combination (one-sided exact binomial test, α=0.05, power 80%). The sample size also ensures sufficient power for key secondary endpoints and supports the translational sub-study (≥28 successful organoid models). Translational Research Component: Pre-treatment tumor biopsies will be used to establish patient-derived organoids (PDOs). Organoids will be characterized (H\&E, immunofluorescence, STR genotyping) and tested ex vivo for sensitivity to MRG003, epirubicin, and their combination. Associations between organoid drug sensitivity and clinical response (ORR, tumor shrinkage, PFS) will be explored. Statistical Analysis: Primary analysis will be performed on the full analysis set (all treated patients). ORR and other binary endpoints will be reported with exact 95% confidence intervals (Clopper-Pearson method). PFS and OS will be estimated using Kaplan-Meier method. Translational data will be analyzed using Spearman rank correlation, Chi-square or Fisher's exact tests, and exploratory Cox regression. Study Duration: Approximately 48 months, including 24 months enrollment, 3-6 months treatment/short-term follow-up per patient, and 24 months long-term survival follow-up after last patient enrollment. Data Monitoring: An independent Data Safety Monitoring Board (DSMB) will conduct interim safety review after 20 patients are enrolled.

Conditions

• Adenoid Cystic Carcinoma
• Sinonasal Carcinoma

Interventions

Type	Name	Description
DRUG	Becotatug Vedotin	Becotatug vedotin (also known as MRG003) is an antibody-drug conjugate (ADC) targeting epidermal growth factor receptor (EGFR). It consists of a recombinant anti-EGFR humanized monoclonal antibody conjugated to the microtubule-disrupting agent monomethyl auristatin E (MMAE) via a valine-citrulline linker. It is administered intravenously at 2.0 mg/kg on day 1 of each 21-day cycle for 3 cycles. Epirubicin is an anthracycline chemotherapeutic agent that inhibits topoisomerase II, thereby interfering with DNA replication and transcription. It is administered intravenously at 75 mg/m² on day 1 of each 21-day cycle for 3 cycles.

Timeline

• Start date: 2026-05-01
• Primary completion: 2028-10-01
• Completion: 2030-07-01
• First posted: 2026-04-13
• Last updated: 2026-04-13