MRG003 Induction and Capecitabine Maintenance With PD-1 in Locally Recurrent NPC

• MRG003 (Drug): MRG003 at 2.0 mg/kg (D1) will be administered every three weeks for 6 cycles
• Tislelizumab (Drug): Tislelizumab 200 mg (D1) will be administered every three weeks for 6 cycles. Upon achieving an objective response, maintenance therapy will continue for up to one year or until disease progression is observed.
• Capecitabine (Drug): After achieving an objective response (ORR) with the combination of MRG003 and Tislelizumab, maintenance therapy will consist of Capecitabine (650 mg/m², administered twice daily on Days 1-21) in conjunction with Tislelizumab. This maintenance phase will continue for up to one year or until disease progression is observed.

Primary outcomes

• Objective Response Rate [Day 21 after the completion of six cycles of MRG003 treatment]: The Objective Response Rate (ORR) is defined as the proportion of patients achieving Complete Response (CR) or Partial Response (PR) by Day 21 after the completion of six cycles of MRG003 treatment, starting from the date of enrollment.

Secondary outcomes

• Progression-Free Survival (PFS) [1-year; 3-year]: PFS is defined as the time from enrollment to the date of tumor progression or death from any cause, or to the date of the last follow-up if no progression has occurred.
• Overall Survival (OS) [1-year; 3-year]: OS is defined as the time from enrollment to the date of death from any cause, or to the date of the last follow-up if no death has occurred.
• Duration of Response (DOR) [1-year; 3-year]: DOR is defined as the time from the first assessment of Complete Response (CR) or Partial Response (PR) to the first assessment of Progressive Disease (PD) or death from any cause
• Disease Control Rate (DCR) [Day 21 after the completion of six cycles of MRG003 treatment]: DCR is defined as the proportion of subjects who achieve Complete Response (CR), Partial Response (PR), or Stable Disease (SD) after treatment.

Sex: All, ages: 18 Years to 70 Years

Inclusion Criteria:

**Inclusion Criteria:**

1. Patients with locally recurrent nasopharyngeal carcinoma (NPC) more than 1 year after initial radical treatment for non-metastatic NPC, with or without regional recurrence, but without distant metastasis.
2. Age 18-70 years.
3. Pathologically confirmed local recurrence of NPC, staged as rT1-rT4 according to the 9th edition of the AJCC/UICC classification.
4. ECOG performance status score of 0-1.
5. No prior radiotherapy, chemotherapy, immunotherapy, or biological therapy for recurrent NPC.
6. No contraindications to immunotherapy or chemotherapy.
7. Adequate organ function.

Exclusion Criteria:

**Exclusion Criteria:**

1. Previous treatment with other PD-1 antibodies or immunotherapy targeting PD-1/PD-L1 resulting in Grade III or higher immune-related adverse reactions.
2. Residual toxic effects from prior anti-tumor treatments (including immunotherapy, targeted therapy, chemotherapy, or radiotherapy) (excluding alopecia, fatigue, and Grade 2 hypothyroidism) or clinically significant laboratory abnormalities higher than Grade 1 (CTCAE v5.0).
3. Congenital or acquired immunodeficiency (e.g., HIV infection), active hepatitis B (HBV-DNA ≥10 copies/ml), or hepatitis C (positive hepatitis C antibody and HCV-RNA above the detection limit of the assay).
4. Known allergy to MRG003, capecitabine, or any component of anti-PD-1 antibodies.