This exploratory clinical study will enroll patients with unresectable locally recurrent nasopharyngeal carcinoma to receive two cycles of becotatug vedotin plus a PD-1 monoclonal antibody, followed by sequential radiotherapy and PD-1 monoclonal antibody maintenance until disease progression or unacceptable toxicity. The study aims to evaluate the efficacy and safety of this treatment strategy.
\*\*Detailed Description\*\* This is an open-label, single-arm, single-center Phase II clinical study. The study will enroll patients with unresectable locally recurrent nasopharyngeal carcinoma. Eligible patients will receive two cycles of induction therapy with becotatug vedotin plus a PD-1 monoclonal antibody, followed by intensity-modulated radiotherapy. During and after radiotherapy, patients will continue PD-1 monoclonal antibody maintenance treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria. The study is designed to evaluate the efficacy and safety of this sequential treatment strategy. The primary endpoint is objective response rate assessed by RECIST v1.1. Secondary endpoints include locoregional recurrence-free survival, progression-free survival, distant metastasis-free survival, 12-month and 24-month progression-free survival rates, overall survival, disease control rate, duration of response, treatment-related adverse events assessed according to NCI-CTCAE v5.0, and quality of life.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
28
Becotatug vedotin will be administered at 2.0 mg/kg intravenously on Day 1 every 3 weeks for 2 cycles as induction therapy, in combination with a PD-1 monoclonal antibody.
Toripalimab will be administered at 240 mg intravenously on Day 1 every 3 weeks. Toripalimab is one of the optional PD-1 monoclonal antibodies in this study and will be used as an alternative to camrelizumab, not in combination with camrelizumab. It will be given during induction therapy, concurrently with radiotherapy, and as maintenance therapy after radiotherapy until disease progression or unacceptable toxicity.
Camrelizumab will be administered at 200 mg intravenously on Day 1 every 3 weeks. Camrelizumab is one of the optional PD-1 monoclonal antibodies in this study and will be used as an alternative to toripalimab, not in combination with toripalimab. It will be given during induction therapy, concurrently with radiotherapy, and as maintenance therapy after radiotherapy until disease progression or unacceptable toxicity.
Objective response rate
The proportion of participants who achieve a complete response (CR) or partial response (PR), as assessed by the investigator according to RECIST v1.1, from the first dose until disease progression, initiation of new anticancer therapy, death, or the last tumor assessment, whichever occurs first.
Time frame: Baseline; end of 2 induction cycles (21 days/cycle); 8-12 weeks after radiotherapy; every 12 weeks through Month 24; then every 24 weeks thereafter until progression, new anticancer therapy, death, or study completion, up to 36months.
Duration of Response (DoR)
For participants who achieve a confirmed complete response (CR) or partial response (PR), duration of response is defined as the time from the first documented CR or PR to the first documented disease progression or death from any cause, whichever occurs first.
Time frame: From first documented CR or PR until first documented disease progression or death, whichever occurs first, assessed up to 36 months.
Locoregional Recurrence-Free Survival (LRFS)
Locoregional recurrence-free survival is defined as the time from the first dose to the first documented locoregional recurrence/progression or death from any cause, whichever occurs first.
Time frame: From the first dose until the first documented locoregional recurrence/progression or death from any cause, whichever occurs first, assessed up to 36 months.
Treatment-Related Adverse Events
Treatment-related adverse events will be assessed and graded according to NCI-CTCAE v5.0. The incidence and severity of adverse events, Grade 3 or higher adverse events, serious adverse events, and adverse events leading to dose modification, treatment interruption, or treatment discontinuation will be summarized.
Time frame: From first dose to 90 days after last study treatment; late radiotherapy-related toxicities followed until Month 24 or study completion.
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Intensity-modulated radiotherapy will be delivered once daily, 5 days per week. Prescribed doses are 60 Gy in 27 fractions to PTVnx, 60-64 Gy in 27 fractions to PTVnd, and 54 Gy in 27 fractions to PTV1.
Overall Survival (OS)
OS is defined as the time from the first dose to death from any cause. Participants who are alive will be censored at the date of last confirmed survival status.
Time frame: From the first dose until death from any cause, assessed up to 36 months.
12-Month Progression-Free Survival Rate
The 12-month PFS rate is defined as the proportion of participants who remain alive and progression-free at 12 months, estimated using the Kaplan-Meier method based on PFS.
Time frame: From the first dose to 12 months.
24-Month Progression-Free Survival Rate
The 24-month PFS rate is defined as the proportion of participants who remain alive and progression-free at 24 months, estimated using the Kaplan-Meier method based on PFS.
Time frame: From the first dose to 24 months.
Progression-Free Survival (PFS)
Progression-free survival is defined as the time from the first dose to the first documented disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first.
Time frame: From the first dose until the first documented disease progression according to RECIST version 1.1 or death from any cause, whichever occurs first, assessed up to 36 months.
Disease Control Rate (DCR)
The proportion of participants who achieve a best overall response of complete response (CR), partial response (PR), or stable disease (SD), as assessed by the investigator according to RECIST version 1.1.
Time frame: Baseline; end of 2 induction cycles (21 days/cycle); 8-12 weeks after radiotherapy; every 12 weeks through Month 24; then every 24 weeks thereafter until progression, death, or study completion, up to 36 months.
Distant Metastasis-Free Survival (DMFS)
DMFS is defined as the time from the first dose to the first documented distant metastasis or death from any cause, whichever occurs first. Distant metastasis will be assessed by imaging examinations, including chest CT, abdominal imaging, bone scan, PET/CT, or other clinically indicated examinations.
Time frame: From first dose until first documented distant metastasis or death, whichever occurs first, assessed up to 36 months.
Quality of Life (QoL)
Quality of life will be assessed using the EORTC QLQ-C30 questionnaires. Scores for each domain and health status will be calculated according to the questionnaire scoring manuals, and changes from baseline will be summarized.
Time frame: Baseline; end of 2 induction cycles (21 days/cycle); end of radiotherapy; 8-12 weeks after radiotherapy; every 12 weeks through Month 24; then every 24 weeks thereafter until study completion, up to 36 months.