Pembrolizumab + MRGOO3 as Neoadjuvant in NPC

NCT07267338 | Not Yet Recruiting Phase 2

• 1 other identifier: MISP102452
• Study Type: interventional
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to evaluate efficacy and safety of neoadjuvant of the anti PD1 agent Pembrolizumab combined with MRG003 and adjuvant treatment of Pembrolizumab in patients with Epstein-Barr virus (EBV) - associated locoregionally advanced nasopharyngeal carcinoma. The expected sample size is 35 patients. Participants will receive 3 cycles of neoadjuvant pembrolizumab 200mg Q3W plus MRG003 2.3mg/kg Q3W followed by the standard concurrent chemoradiotherapy. Then participants will receive 14 cycles of adjuvant Pembrolizumab 200 mg Q3W after the standard concurrent chemoradiotherapy. The estimated average length of treatment per patients is 1 year.

Conditions

Locoregionally Advanced Nasopharyngeal Carcinoma; NPC

Outcome Measures

Primary Outcomes (1)

• Clinical Complete Response (cCR) rate

  clinical complete response (cCR) rate to neoadjuvant treatment.

  cCR assessment will be performed on week 9±7 days between neoadjuvant therapy and pre CCRT

Secondary Outcomes (3)

• Objective Response Rate (ORR)

  To assess the objective response rate of Neoadjuvant therapy of Pembrolizumab in combination with MRG003 at maximum of 9 weeks (up to 3 cycles)

• Event-Free Survival (EFS)

  Defined as the time from date of treatment to the date of first documented disease progression that precluded definitive surgery, local or distant recurrence, occurrence of a second primary cancer or death from any cause, up to 36 months

• Overall Survival (OS)

  OS, defined as the time from the date of treatment to the date of death due to any cause, up to 60 months

Study Arms (1)

Treatment group

EXPERIMENTAL

Participants will receive 3 cycles of neoadjuvant Pembrolizumab 200 mg IV every 3 weeks (Q3W) combined MRG003 2.0mg/kg IV Q3W followed by standard CCRT and adjuvant treatment of Pembrolizumab 200 mg IV Q3W up to 14 cycles.

Drug: Pembrolizumab & MRG003

Interventions

Pembrolizumab & MRG003 DRUG

After a screening phase of up to 28 days, each subject will be assigned to receive treatment until disease progression is confirmed, unacceptable adverse event(s), intercurrent illness that prevents further administration of treatment, investigator's decision to withdraw the subject, or until subjects has received up to 3 cycles pembrolizumab + MRG003, followed Standard concurrent chemoradiotherapy (CCRT), followed up to 14 cycles pembrolizumab.

Treatment group

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Male/female participants who are at least 18 years of age on the day of signing informed consent with histologically confirmed diagnosis of stage III-IVa (Exclude T3N0) nasopharyngeal carcinoma (NPC) will be enrolled in this study.
• The participant (or legally acceptable representative if applicable) provides written informed consent for the trial.
• Have measurable disease based on RECIST 1.1. Lesions situated in a previously irradiated area are considered measurable if progression has been demonstrated in such lesions.
• Archival tumor tissue sample or newly obtained \[core or excisional\] biopsy of a tumor lesion not previously irradiated has been provided. Formalin-fixed, paraffin embedded (FFPE) tissue blocks are preferred to slide. Newly obtained biopsies are preferred to archived tissue.
• Have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1. Evaluation of ECOG is to be performed within 7 days prior to the first dose of study intervention.
• Epsitein-Barr virus-encoded RNA(EBER) positive.
• Epidermal Growth Factor Receptor (EGFR) positive.
• Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication.
• Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 120 days after the last dose of study therapy.
• Have adequate organ function. Specimens must be collected within 10 days prior to the start of study intervention.

You may not qualify if:

• Presence of any distant metastasis.
• Has received prior therapy with EGFR target therapy, or an anti-PD-1, anti-PD-L1, or anti PD L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX 40, CD137).
• Has received prior systemic anti-cancer therapy including investigational agents within 4 weeks \[could consider shorter interval for kinase inhibitors or other short half-life drugs\] prior to \[allocation\].
• Has received prior radiotherapy within 2 weeks of start of study intervention or radiation-related toxicities requiring corticosteroids. Note: Two weeks or fewer of palliative radiotherapy for non-CNS disease is permitted. The last radiotherapy treatment must have been performed at least 7 days before the first dose of study intervention.
• Has received a live vaccine or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed.
• Has received an investigational agent or has used an investigational device within 4 weeks prior to study intervention administration.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
• Known additional malignancy that is progressing or has required active treatment within the past 3 years. Note: Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ, excluding carcinoma in situ of the bladder, that have undergone potentially curative therapy are not excluded. Participants with low-risk early-stage prostate cancer (T1-T2a, Gleason score ≤6, and PSA \<10 ng/mL) either treated with definitive intent or untreated in active surveillance with stable disease are not excluded.
• Has known active CNS metastases and/or carcinomatous meningitis. Participants with previously treated brain metastases may participate provided they are radiologically stable, i.e., without evidence of progression for at least 4 weeks by repeat imaging (note that the repeat imaging should be performed during study screening), clinically stable and without requirement of steroid treatment for at least 14 days prior to first dose of study intervention.
• Has severe hypersensitivity (≥Grade 3) to pembrolizumab, MRG003 and/or any of its excipients.
• Has active autoimmune disease that has required systemic treatment in the past 2 years except replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid)
• Has a history of (non-infectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
• Has an active infection requiring systemic therapy.
• History of Hepatitis B (defined as HBsAg reactive) or known active Hepatitis C virus (defined as detectable HCV RNA \[qualitative\]) infection.
• Note: Testing for Hepatitis B or C is not required unless mandated by local health authority.

Sponsors & Collaborators

• Union Hospital, Tongji Medical College, Huazhong University of Science and Technology: lead
• Merck Sharp & Dohme LLC: collaborator
• Lepu Medical Technology (Beijing) Co., Ltd.: collaborator

Study Sites (1)

Wuhan Xiehe Hospital

Wuhan, Hubei, China

Location

MeSH Terms

Interventions

pembrolizumab

Central Study Contacts

Lu Wen, Doctor

CONTACT

0086-027-83262661; wenlu2808@126.com

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 17, 2025
• First Posted: December 5, 2025
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): June 1, 2029
• Last Updated: December 5, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

CN (1)