QL1706 (PD-1/CTLA-4 Bi-specific Antibody) and Chemoradiotherapy in Locoregionally-advanced Nasopharyngeal Carcinoma.

Phase 3

Recruiting

• Conditions: Nasopharyngeal Cancinoma (NPC); Nasopharyngeal Cancer
• Interventions: Drug: QL1706; Drug: Gemcitabine; Drug: Cisplatin; Radiation: Intensity-modulated radiotherapy

• Registration Number: NCT06749899
• Lead Sponsor: Sun Yat-sen University

Brief Summary

The trial aimed to compare QL1706 combined with induction chemotherapy plus concurrent chemoradiotherapy (IC+CCRT) versus IC+CCRT alone in High-risk Locoregionally-Advanced Nasopharyngeal Carcinoma (LANPC).

Detailed Description

The trial plans to enroll patients with stage T4N1and T1-4N2-3 (AJCC 9th) locoregionally-advanced nasopharyngeal carcinoma (LANPC). Patients will be randomized in a 1:1 ratio to receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin and concurrent cisplatin-radiation or the same regimen plus QL1706 in induction chemotherapy and adjuvant chemotherapy. All patients will receive intensity-modulated radiotherapy (IMRT). QL1706 will begin on day 1 of induction chemotherapy and continue every 3 weeks for 3 cycles in induction therapy and for 9 cycles in adjuvant therapy.

Study Timeline

• Status Verified: 2024-12
• Study First Submitted: 2024-12-19
• Study First Submitted QC: 2024-12-23
• Study First Posted: 2024-12-27
• Study Start: 2025-05-04
• Last Update Submitted: 2025-05-19
• Last Update Posted: 2025-05-22
• Primary Completion: 2028-12-01
• Study Completion: 2030-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 580

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
QL1706 Arm	QL1706	Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. QL1706 5mg/kg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 9 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.
QL1706 Arm	Gemcitabine	Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. QL1706 5mg/kg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 9 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.
QL1706 Arm	Cisplatin	Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. QL1706 5mg/kg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 9 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.
QL1706 Arm	Intensity-modulated radiotherapy	Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT. QL1706 5mg/kg will be given every 3 weeks for 3 cycles in induction chemotherapy and for 9 cycles in adjuvant chemotherapy, started on day 1 of induction chemotherapy and adjuvant chemotherapy, respectively.
Chemoradiation Arm	Gemcitabine	Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT.
Chemoradiation Arm	Cisplatin	Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT.
Chemoradiation Arm	Intensity-modulated radiotherapy	Patients will receive induction chemotherapy with gemcitabine (1g/m2, d1 \& 8 of every cycle) and cisplatin (80mg/m2, d1 of every cycle), every 3 weeks for 3 cycles before radiation. Definitive intensity-modulated radiotherapy (IMRT) of 6996cGy in 33 fractions will be given. Concurrent cisplatin of 100mg/m2 will be administered every 3 weeks for 2 cycles during IMRT.

Primary Outcome Measures

Name	Time	Method
Failure-free survival (FFS) in intention-to-treat population	3 years	Multiple endpoint 1: calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.
Overall survival (OS) in intention-to-treat population	5 years	Multiple endpoint 2: calculated from randomization to the date of death from any cause.

Secondary Outcome Measures

Name	Time	Method
Failure-free survival (FFS) in per-protocol population	3 years	calculated from randomization to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first.
Overall survival (OS) in per-protocol population	3 years	calculated from randomization to the date of death from any cause.
Locoregional recurrence-free survival (LRRFS)	3 years	calculated from randomization to the date of locoregional persistence or 1st locoregional recurrence.
Distant metastasis-free survival (DMFS)	3 years	calculated from randomization to the date of first distant metastasis.
Adverse events (AEs) and serious adverse events (SAEs)	3 years	Graded according to CTCAE V5.0.
Quality of life (QoL)	week 1, 20, 40, 64	The change of QoL from randomization to the start of radiotherapy, the end of radiotherapy, 13-16 weeks after radiotherapy, 2 years and 3 years after randomization. The EORTC QoL questionnaire-C30 (EORTC QLQ-C30）version 3.0 will be used. This questionnaire comprises 30 questions, 24 of which are aggregated into nine multi-question scales, that is, five functioning scales (e.g., physical), three symptom scales (e.g., fatigue) and one global health status scale. The remaining six single-question (e.g., dyspnoea) scales assess symptoms. These 15 scales will be scored according to the official Scoring Manual.
Failure-free survival (FFS) within different subgroups	3 years	analyses for FFS will be performed within the following subgroups: Epstein-Barr virus (EBV) DNA (≤4000copies/ml vs. \>4000copies/ml), different PD-L1 expression levels, age, gender, performance status, T category, N category, and stage (III vs. IVA).
Tumor response	Every 6 weeks（the time of completion of induction chemotherapy, radiotherapy, and adjuvnt immunotherapy; from the date of enrollment until the date of the last time that tumorimaging and assessment of disease has been done, assessed up to 74 weeks)	Evaluation of tumor response as CR, PR, SD, PD, NA by clinicians

Trial Locations

Locations (19)

Fujian Cancer Hospital; 🇨🇳 Fuzhou,, Fujian, China

Dongguan People's Hospital; 🇨🇳 Dongguan, Guangdong, China

First People's Hospital of Foshan; 🇨🇳 FoShan, Guangdong, China

Guangzhou Panyu Central Hospital; 🇨🇳 Guangzhou, Guangdong, China

Sun Yat-Sen University Cancer Center; 🇨🇳 GuangZhou, Guangdong, China

Zhongshan People's Hospital; 🇨🇳 Zhongshan, Guangdong, China

Cancer Hospital of Guangxi Medical University; 🇨🇳 Nanning, Guangxi, China

Cancer Hospital of Guizhou Medical University; 🇨🇳 Guiyang, Guizhou, China

Hubei Province Cancer Hosiptal; 🇨🇳 WuHan, Hubei, China

Renmin Hospital of Wuhan University; 🇨🇳 Wuhan, Hubei, China

Union Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology; 🇨🇳 Wuhan, Hubei, China

Tongji Hospital Affiliated with Tongji Medical College of Huazhong University of Science and Technology; 🇨🇳 WuHan, Hubei, China

Hunan Cancer Hospital; 🇨🇳 ChangSha, Hunan, China

Xiangya Hospital of Central South University; 🇨🇳 ChangSha, Hunan, China

Jiangsu Cancer Hospital; 🇨🇳 Nanjing, Jiangsu, China

The Eye and ENT Hospital of Fudan University; 🇨🇳 Shanghai, Shanghai, China

Sichuan Cancer Hospital; 🇨🇳 Chengdu, Sichuan, China

Tianjin Medical University Cancer Institute ＆ Hospital; 🇨🇳 Tianjin, Tianjin, China

The First Affiliated Hospital of Xiamen University; 🇨🇳 Fujian, Xiamen, China