Becotatug Vedotin for Locoregionally Advanced Nasopharyngeal Carcinoma With a Suboptimal Response to Induction Chemotherapy Combined With Immunotherapy: A Prospective, Single-Arm, Phase II Trial
Overview
- Phase
- Phase 2
- Status
- Recruiting
- Sponsor
- Sun Yat-sen University
- Enrollment
- 59
- Locations
- 1
- Primary Endpoint
- Progression-free survival
Overview
Brief Summary
Based on the short-term efficacy and plasma EBV DNA levels following immuno-induction chemotherapy, patients with locally advanced nasopharyngeal carcinoma who derive different benefits from this treatment can be identified. For high-risk patients who do not respond to immuno-induction chemotherapy (defined as EBV DNA >0 copies/mL or imaging response evaluation showing SD/PD after immuno-induction chemotherapy), the addition of becotatug vedotin, which has a different mechanism of action, during concurrent radiotherapy and the adjuvant phase may improve patient survival. Based on the above research and background, the investigators plan to conduct the first prospective, single-arm, phase II clinical study of becotatug vedotin in patients with locally advanced nasopharyngeal carcinoma who are suboptimal responsive to immuno-induction chemotherapy, aiming to obtain sufficient evidence-based medical data to provide an additional treatment option for the concurrent and adjuvant phases of nasopharyngeal carcinoma.
Study Design
- Study Type
- Interventional
- Allocation
- Na
- Intervention Model
- Single Group
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 70 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Voluntary participation and written informed consent must be signed.
- •Age between 18 and 70 years, male or non-pregnant female.
- •Pathologically confirmed nasopharyngeal non-keratinizing carcinoma (differentiated or undifferentiated type, i.e., WHO type II or type III).
- •Stage Any T N2-3 or T4N1 (AJCC 9th edition), with no distant metastasis, and previously untreated nasopharyngeal carcinoma.
- •Efficacy after 3 cycles of induction immunochemotherapy assessed as stable disease (SD) or progressive disease (PD) by nasopharyngoscopy and contrast-enhanced MRI of the nasopharynx and neck.
- •ECOG performance status score of 0 or
- •Adequate hematological function: Hemoglobin (HGB)≥90g/L, White Blood Cell (WBC) ≥ 4.010\^9/L, and Platele (PLT) ≥10010\^9/L.
- •Adequate hepatic function: ALT and AST≤2.5Upper Limit of Normal (ULN), total bilirubin ≤2.0ULN, and serum albumin≥30g/L.
- •Adequate renal function: Serum creatinine ≤ 1.5\*ULN or calculated creatinine clearance (CrCl) ≥ 60 mL/min (using the Cockcroft-Gault formula).
- •International Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤ 1.5 \*ULN (unless the subject is receiving anticoagulant therapy and the coagulation parameters (PT/INR and APTT) are within the expected therapeutic range for the anticoagulant at the time of screening).
Exclusion Criteria
- •Patients with recurrent or distant metastatic nasopharyngeal carcinoma.
- •Pathological diagnosis of keratinizing squamous cell carcinoma (WHO Type I).
- •Patients who have previously received radiotherapy or systemic chemotherapy.
- •Women who are pregnant or breastfeeding, or individuals of childbearing potential who are not using effective contraception.
- •HIV positive.
- •History of other malignancies (except for cured basal cell carcinoma or cervical carcinoma in situ).
- •Patients who have previously received immune checkpoint inhibitors (e.g., CTLA-4, PD-1, PD-L1 inhibitors).
Arms & Interventions
Experimental arm
- Induction Chemotherapy (TPP Regimen) Docetaxel 75 mg/m² d1 + Cisplatin (DDP) 75 mg/m² d1 + PD-1 inhibitor , administered every 3 weeks for a total of 3 cycles.
- Concurrent Radiotherapy (Becotatug vedotin + IMRT)
Concurrent radiotherapy commences 3 weeks after the completion of induction chemotherapy:
Becotatug vedotin 2.3 mg/kg d1, starting on the first day of radiotherapy, administered every 3 weeks during the radiotherapy period for a total of 3 cycles.
The radiotherapy technique employed is intensity-modulated radiotherapy (IMRT). 3. Adjuvant Therapy
Adjuvant therapy commences 4-6 weeks after the completion of radiotherapy:
Becotatug vedotin 2.3 mg/kg d1, administered every 3 weeks for a total of 3 cycles.
Intervention: Becotatug vedotin (Drug)
Outcomes
Primary Outcomes
Progression-free survival
Time Frame: 3 years
Progression-free survival is calculated from the date of treatment initiation to the date of documented local or regional relapse, distant metastasis, or death from any cause, whichever occurred first.
Secondary Outcomes
- Overall survival(3 years)
- Locoregional recurrence-free survival(3 years)
- Distant metastasis-free survival(3 years)
- Incidence of acute toxicity as assessed by CTCAE v5.0(3 years)
- Incidence of late toxicity as assessed by the Late Radiation Morbidity Scoring Scheme of the Radiation Therapy Oncology Group(3 years)
Investigators
Pei-Yu Huang
Principal Investigator
Sun Yat-sen University