Nasopharyngeal Carcinoma (NPC)
Conditions
Keywords
PD-1/VEGF bispecific antibody, Chemoradiotherapy, Anti-PD-1 Therapy, Ivonescimab, Immunotherapy, Bispecific Antibody
Brief summary
This trial aims to study the role of Ivonescimab combined with chemoradiotherapy in high-Risk locoregionally advanced nasopharyngeal carcinoma.
Detailed description
The trial plans to enroll patients with T3N2M0+ Stage III (AJCC 9th) locoregionally advanced nasopharyngeal carcinoma (LANPC). Patients will receive 3 cycles of induction chemotherapy with gemcitabine and cisplatin combined with ivonescimab, followed by concurrent chemoradiotherapy with cisplatin, and then 9 cycles of adjuvant ivonescimab. Ivonescimab will be administered every 3 weeks starting from day 1 of induction therapy and continued through the adjuvant phase.
Interventions
Ivonescimab (AK112) is a novel PD-1/VEGF bispecific antibody designed to simultaneously block PD-1-mediated immune evasion and inhibit VEGF-driven angiogenesis. In this study, ivonescimab is administered intravenously at a dose of 10 mg/kg every 3 weeks, starting on Day 1 of induction chemotherapy (3 cycles), followed by concurrent chemoradiotherapy (no ivonescimab), and then continued as adjuvant monotherapy for 9 additional cycles.
Sponsors
Sun Yat-sen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
1. Age between 18 and 65 years. 2. Histologically confirmed non-keratinizing carcinoma (according to WHO classification). 3. ECOG performance status of 0 or 1. 4. Previously untreated nasopharyngeal carcinoma staged as T3N2M0 or Stage III according to the AJCC 9th edition. 5. Adequate bone marrow function, defined as white blood cell count \> 4×10⁹/L, hemoglobin \> 90 g/L, and platelet count \> 100×10⁹/L. 6. Adequate liver and renal function, defined as total bilirubin ≤ 1.5 × ULN; AST and/or ALT ≤ 2.5 × ULN; alkaline phosphatase ≤ 2.5 × ULN; and creatinine clearance ≥ 60 mL/min. 7. Normal thyroid function, amylase, lipase, pituitary function, inflammatory markers, myocardial enzymes, and ECG. For patients over 50 years old with a smoking history, pulmonary function test results must be normal. For patients with ECG abnormalities or a cardiovascular history not meeting
Exclusion criteria
#8, echocardiography and cardiac function tests must be normal. 8. Signed informed consent and willingness to comply with all scheduled visits, treatment procedures, laboratory tests, and other study-related requirements. 9. Female participants of childbearing potential and male participants with female partners of childbearing potential must agree to use reliable contraception from screening until 1 year after completion of treatment.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Complete response rate (CRR) | At the end of induction therapy | Disappearance of all target lesions, with all pathological lymph nodes (including both target and non-target nodes) reduced in short axis to less than 10 mm. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Failure-free survival (FFS) | 2 years | calculated from enrolment to the date of locoregional recurrence, distant metastasis, or death from any cause, whichever occurred first. |
| Overall survival (OS) | 2 years | calculated from enrolment to the date of death from any cause. |
| Distant metastasis-free survival (DMFS) | 2 years | calculated from enrolment to the date of first distant metastasis. |
| Objective response rate (ORR) | At the end of induction therapy | Objective Response Rate (ORR) is defined as the proportion of patients who achieve either a Complete Response (CR) or a Partial Response (PR) as assessed per RECIST v1.1 criteria. |
| Adverse events (AEs) and serious adverse events (SAEs) | 2 years | Analysis of adverse events (AEs) are based on treatmentrelated AEs (trAEs) and immune-related AEs (irAEs), and all-grade AEs and grade 3-4 AEs. Graded according to CTCAE V5.0. |
| Quality of life (QoL) | 2 years | Change in quality of life (QoL) will be assessed at six time points: prior to enrollment (baseline), after completion of induction immunotherapy, after completion of concurrent chemoradiotherapy, after the 5th cycle of adjuvant immunotherapy, after completion of all adjuvant immunotherapy, and at 6 months following the end of adjuvant immunotherapy. The European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30), version 3.0, will be used. This validated instrument contains 30 items, of which 24 are grouped into nine multi-item scales: five functional scales, three symptom scales, and one global health status/QoL scale. The remaining six items are single-item symptom scales. All 15 scales will be scored according to the EORTC QLQ-C30 Scoring Manual.Each scale is linearly transformed to a 0-100 scale. Higher scores indicate better functioning and QoL on functional and global health scales, but worse symptoms on symptom scales. |
| Locoregional recurrence-free survival (LRRFS) | 2 years | calculated from enrolment to the date of locoregional persistence or 1st locoregional recurrence. |
Countries
China
Contacts
Primary ContactJun Ma, M.D.
Backup ContactLei Chen, M.D.
Outcome results
None listed