This randomized controlled trial aims to evaluate the efficacy and safety of Becotatug Vedotin (MRG003), an antibody-drug conjugate (ADC), combined with the PD-1 inhibitor Pucotenlimab as induction therapy for high-risk locoregionally advanced nasopharyngeal carcinoma (NPC), compared to the standard gemcitabine and cisplatin (GP) regimen combined with Pucotenlimab, followed by concurrent chemoradiotherapy (CCRT) and adjuvant immunotherapy.
Patients in the experimental arm will receive MRG003 (2.0 mg/kg, Day 1, Q3W × 3 cycles) plus Pucotenlimab (200 mg, Day 1, Q3W × 3 cycles) as induction therapy, followed by CCRT \[intensity-modulated radiotherapy (IMRT): 70 Gy in 33 fractions, 5 days/week, once daily; cisplatin 100 mg/m², Day 1, Q3W × 2 cycles\], and adjuvant Pucotenlimab (200 mg, Day 1, Q3W × 6 cycles). Patients in the control arm will receive gemcitabine (1000 mg/m², Days 1 and 8, Q3W × 3 cycles) plus cisplatin (80 mg/m², Day 1, Q3W × 3 cycles) and Pucotenlimab (200 mg, Day 1, Q3W × 3 cycles) as induction therapy, followed by the same CCRT regimen and adjuvant Pucotenlimab. The primary objectives are to assess whether ADC-based induction therapy improves the post-induction therapy complete response rate (post-IT CRR) and event-free survival (EFS) compared to the GP-based standard of care. Secondary objectives include comparisons of overall survival (OS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRRFS), as well as evaluation of the safety, tolerability, and quality of life associated with the MRG003-containing regimen.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
514
Induction Therapy: Becotatug Vedotin (MRG003) 2.0 mg/kg, intravenous infusion, Day 1 (3 cycles, Q3W)
Induction Therapy: Pucotenlimab 200 mg, intravenous infusion, Day 1 (3 cycles, Q3W); Adjuvant Therapy: Pucotenlimab 200 mg, intravenous infusion, Day 1 (6 cycles, Q3W)
Induction Therapy (3 cycles, Q3W): Gemcitabine 1000 mg/m², intravenous infusion, Days 1 and 8 Cisplatin 80 mg/m², intravenous infusion, Day 1
70 Gy in 33 fractions, once daily, 5 days per week
Concurrent Cisplatin: 100 mg/m², intravenous infusion, Day 1 (2 cycles, Q3W) during radiation
Post-induction Therapy Complete Response Rate (post-IT CRR)
The proportion of patients achieving complete response following induction therapy
Time frame: Within 9 to 21 days after the last dose of induction therapy
Event-Free Survival (EFS)
From date of randomization until the date of first documented locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.
Time frame: 3 years & 5 years
Overall survival (OS)
From date of enrollment to date of death from any cause
Time frame: 3 years & 5 years
Distant Metastasis-Free Survival (DMFS)
From date of enrollment to date of first documented distant metastasis
Time frame: 3 years & 5 years
Locoregional Recurrence-Free Survival (LRRFS)
From date of enrollment to date of first documented locoregional recurrence
Time frame: 3 years & 5 years
Adverse Events (AEs)
Graded according to CTCAE V5.0
Time frame: 3 years & 5 years
Patient-Reported Adverse Events (PRO-CTCAE)
Patient-reported adverse events will be assessed using selected items from the National Cancer Institute Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (NCI PRO-CTCAE™), Chinese version, administered at each treatment cycle. Patients will self-report and rate the severity of relevant adverse events throughout the study treatment period.
Time frame: At the end of each treatment cycle (each cycle is 21 days), from Cycle 1 of induction therapy through Cycle 6 of adjuvant therapy
European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score
Assesses general quality of life in cancer patients. Items are scored and linearly transformed to a 0-100 scale. For functional scales, higher scores indicate better functioning; for symptom scales, higher scores indicate greater symptom burden.
Time frame: At baseline, after completion of induction therapy (Week 10), mid-IMRT(Week 16), after completion of IMRT (Week 19), at the last adjuvant cycle (Week 34; each cycle is 21 days), and at 3, 12, 24, 36, 48, and 60 months post-radiotherapy
EORTC Quality of Life Questionnaire Head and Neck 35 (EORTC QLQ-H&N35, version 1)
Assesses head and neck cancer-specific symptoms. Items are scored and linearly transformed to a 0-100 scale. Higher scores indicate more severe symptoms.
Time frame: At baseline, after completion of induction therapy (Week 10), mid-IMRT(Week 16), after completion of IMRT (Week 19), at the last adjuvant cycle (Week 34; each cycle is 21 days), and at 3, 12, 24, 36, 48, and 60 months post-radiotherapy
Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N, Chinese version 4)
Assesses quality of life specific to head and neck cancer patients. Items are rated on a 0-4 scale and summed to a total score of 0-156. Higher scores indicate better quality of life.
Time frame: At baseline, after completion of induction therapy (Week 10), mid-IMRT(Week 16), after completion of IMRT (Week 19), at the last adjuvant cycle (Week 34; each cycle is 21 days), and at 3, 12, 24, 36, 48, and 60 months post-radiotherapy
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.