Nasopharyngeal Cancinoma (NPC), Nasopharyngeal Cancer
Conditions
Keywords
PD-1 antibody, Antibody-Drug Conjugate, MRG003, Becotatug Vedotin, Pucotenlimab
Brief summary
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.
Detailed description
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.
Interventions
Induction Therapy: Becotatug Vedotin (MRG003) 2.0 mg/kg, intravenous infusion, Day 1 (3 cycles, Q3W)
DRUGPucotenlimab
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
RADIATIONintensity-modulated radiotherapy
70 Gy in 33 fractions, once daily, 5 days per week
DRUGCisplatin
Concurrent Cisplatin: 100 mg/m², intravenous infusion, Day 1 (2 cycles, Q3W) during radiation
Sponsors
Sun Yat-sen University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 1\. Age ≥ 18 years at the time of diagnosis, regardless of sex 2\. Histologically confirmed newly diagnosed nasopharyngeal carcinoma (NPC) of non-keratinizing carcinoma histology (WHO classification) 3\. Locoregionally advanced NPC staged as T4N2 or T1-4N3 according to the American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) 9th edition staging system. All patients must undergo the following evaluations prior to initiation of any treatment to confirm clinical staging: complete medical history and physical examination, complete blood count (CBC) and biochemistry panel, plasma Epstein-Barr virus (EBV) DNA titer and serology, nasopharyngoscopy, magnetic resonance imaging (MRI) of the head and neck, chest X-ray or computed tomography (CT) of the chest, abdominal ultrasound, and bone scintigraphy. 18F-fluorodeoxyglucose positron emission tomography/CT (¹⁸F-FDG PET/CT) may be used as a substitute for the latter three imaging modalities. 4\. At least one measurable lesion as defined by Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) 5\. Willing to provide archived tumor tissue (primary or metastatic lesion, obtained within 2 years prior to enrollment) or fresh biopsy specimen. Patients unable to provide tumor tissue may still be enrolled at the investigator's discretion, provided all other eligibility criteria are met. 6\. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 7 days prior to first dose 7\. Adequate organ function, as defined by the following laboratory parameters, obtained within 4 weeks prior to screening, with no blood transfusions, hematopoietic growth factors, or thrombopoietic agents administered during this period: a) Hematology: Absolute neutrophil count (ANC) ≥ 1.5 × 10⁹/L; white blood cell count \> 4 × 10⁹/L; hemoglobin \> 90 g/L; platelet count \> 100 × 10⁹/L; b) Hepatic and renal function: Serum total bilirubin (TBIL) ≤ 1.5 × upper limit of normal (ULN); aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) ≤ 2.5 × ULN; alkaline phosphatase (ALP) ≤ 2.5 × ULN; creatinine clearance ≥ 60 mL/min; urinary protein ≤ 2+ or ≤ 1000 mg/24 hours; c) Coagulation: International normalized ratio (INR) ≤ 1.5 × ULN and activated partial thromboplastin time (APTT) ≤ 1.5 × ULN (patients receiving stable low-dose anticoagulation therapy, such as aspirin 100 mg/day, are permitted) 8\. Normal findings on thyroid function tests, serum amylase and lipase, pituitary function tests, inflammatory and infectious markers, cardiac enzyme panel, and electrocardiogram (ECG): a) Patients aged \> 50 years with a smoking history must have normal pulmonary function test results; b) Patients with ECG abnormalities or a prior cardiovascular history (not meeting
Exclusion criteria
) must additionally undergo myocardial function testing and echocardiography, with normal results required for enrollment 9\. Willing and able to provide written informed consent and to comply with all protocol-specified requirements, including scheduled visits, treatment administration, laboratory assessments, and other study procedures 10\. Patients of reproductive potential must agree to use effective contraception from the time of informed consent through 6 months after the last dose of study treatment. Women of childbearing potential (WOCBP), defined as premenopausal women and women within 2 years of menopause, must have a negative serum pregnancy test within 7 days prior to the first dose of study treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Post-induction Therapy Complete Response Rate (post-IT CRR) | Within 9 to 21 days after the last dose of induction therapy | The proportion of patients achieving complete response following induction therapy |
| Event-Free Survival (EFS) | 3 years & 5 years | From date of randomization until the date of first documented locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Overall survival (OS) | 3 years & 5 years | From date of enrollment to date of death from any cause |
| Distant Metastasis-Free Survival (DMFS) | 3 years & 5 years | From date of enrollment to date of first documented distant metastasis |
| Locoregional Recurrence-Free Survival (LRRFS) | 3 years & 5 years | From date of enrollment to date of first documented locoregional recurrence |
| Adverse Events (AEs) | 3 years & 5 years | Graded according to CTCAE V5.0 |
| Patient-Reported Adverse Events (PRO-CTCAE) | At the end of each treatment cycle (each cycle is 21 days), from Cycle 1 of induction therapy through Cycle 6 of adjuvant therapy | 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. |
| European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) Score | 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 | 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. |
| EORTC Quality of Life Questionnaire Head and Neck 35 (EORTC QLQ-H&N35, version 1) | 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 | Assesses head and neck cancer-specific symptoms. Items are scored and linearly transformed to a 0-100 scale. Higher scores indicate more severe symptoms. |
| Functional Assessment of Cancer Therapy - Head and Neck (FACT-H&N, Chinese version 4) | 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 | 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. |
Contacts
CONTACTJun Ma
CONTACTWei Jiang
Outcome results
None listed