Timing Optimization of Immunotherapy During Neoadjuvant Chemotherapy for Locally Advanced Nasopharyngeal Carcinoma

A Multicenter, Randomized, Phase II Clinical Trial to Optimize the Timing of Immune Checkpoint Inhibitor Administration During Neoadjuvant Chemotherapy in Patients With Locally Advanced Nasopharyngeal Carcinoma

This is a multicenter, open-label, randomized phase II clinical trial designed to evaluate the optimal timing of toripalimab administration during neoadjuvant chemotherapy in patients with locoregionally advanced nasopharyngeal carcinoma. Participants will receive gemcitabine and cisplatin (GP) chemotherapy combined with toripalimab administered on different days (Day 1, Day 5, or Day 9) to compare treatment responses. The neoadjuvant phase includes 3 cycles of 21 days each, followed by concurrent chemoradiotherapy. The estimated enrollment period is from March 2026 to March 2028.

Study Overview

• Status: Not yet recruiting
• Conditions: Locally Advanced Nasopharyngeal Carcinoma
• Intervention / Treatment: Drug: Toripalimab; Drug: Toripalimab

• Study Type: Interventional
• Enrollment (Estimated): 198
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Yedong Huang, MD. PhD; Phone Number: 86+15959678182; Email: drhuangyd@163.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Age between 18 and 70 years

Histologically confirmed locoregionally advanced nasopharyngeal carcinoma (AJCC/UICC 8th edition stage II-III)

At least one measurable target lesion per RECIST 1.1

ECOG performance status of 0-1

Estimated life expectancy ≥ 6 months

Adequate hematologic, hepatic, renal, and coagulation function

Negative pregnancy test for women of childbearing potential

Willingness to use effective contraception during the study and for 12 months after treatment

Signed informed consent

Willing and able to comply with study procedures

Not participating in any other interventional clinical trials during the study period

Exclusion Criteria:

• re first dose

Active or suspected autoimmune disease requiring systemic treatment

Ongoing systemic immunosuppressive therapy

Active hepatitis B, hepatitis C, HIV infection, or other serious infections

History of another malignancy within 5 years (except non-melanoma skin cancer or in situ cervical cancer)

Pregnant or breastfeeding women

Inability or unwillingness to use contraception as required

Life expectancy < 6 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Control Arm; Participants receive gemcitabine and cisplatin chemotherapy combined with toripalimab administered on Day 1 of each 21-day cycle for 3 cycles.
Experimental: Experimental Arm; Participants receive gemcitabine and cisplatin chemotherapy combined with toripalimab administered on Day 9 of each 21-day cycle for 3 cycles.	Drug: Toripalimab; Toripalimab 240 mg IV on Day 9, every 21-day cycle, for 3 cycles.; Drug: Toripalimab; Toripalimab 240 mg IV on Day 5 depending, every 21-day cycle, for 3 cycles.
Experimental: Exploratory Arm; Participants receive gemcitabine and cisplatin chemotherapy combined with toripalimab administered on Day 5 of each 21-day cycle for 3 cycles. This arm is exploratory in nature with a smaller sample size.	Drug: Toripalimab; Toripalimab 240 mg IV on Day 9, every 21-day cycle, for 3 cycles.; Drug: Toripalimab; Toripalimab 240 mg IV on Day 5 depending, every 21-day cycle, for 3 cycles.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Complete Response Rate	The proportion of participants achieving complete response (CR) after 2 cycles of neoadjuvant chemotherapy combined with toripalimab, as assessed by RECIST or institutional imaging criteria.	After 2 cycles of neoadjuvant therapy (21-28 days for each cycle)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response Rate	The proportion of participants achieving complete response (CR) or partial response (PR) after 2 cycles of neoadjuvant chemo-immunotherapy.	After 2 cycles of neoadjuvant therapy (21-28 days for each cycle)
Disease Control Rate	The proportion of participants with CR, PR, or stable disease (SD) after 2 cycles of neoadjuvant chemo-immunotherapy.	After 2 cycles of neoadjuvant therapy (21-28 days for each cycle)
EBV DNA Clearance Rate	The proportion of participants with undetectable plasma Epstein-Barr virus (EBV) DNA levels after 2 cycles of neoadjuvant chemo-immunotherapy.	After 2 cycles of neoadjuvant therapy (21-28 days for each cycle)
Incidence of Grade ≥3 Treatment-Related Adverse Events	The frequency of treatment-related adverse events (AEs) of grade 3 or higher, according to CTCAE version 5.0.	From first dose until 30 days after the end of neoadjuvant therapy

Collaborators and Investigators

• Sponsor: Fujian Cancer Hospital

Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): May 1, 2028

Study Registration Dates

• First Submitted: January 15, 2026
• First Submitted That Met QC Criteria: January 28, 2026
• First Posted (Actual): February 5, 2026

Study Record Updates

• Last Update Posted (Actual): February 5, 2026
• Last Update Submitted That Met QC Criteria: January 28, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: toripalimab
• Other Study ID Numbers: 2026-01-15

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No