Neoadjuvant Becotatug Vedotin (Anti-EGFR ADC) Combined With Pucotenlimab (Anti-PD-1) in Patients With Resectable Recurrent Head and Neck Squamous Cell Carcinoma Who Progressed on Prior PD-1/PD-L1 Inhibitor and Platinum-Based Therapy: A Prospective, Single-Arm, Multi-Center, Phase II Clinical Trial
试验速览
- 阶段
- 2 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 42
- 试验地点
- 12
研究概览
简要总结
This is a prospective, single-arm, multi-center, Phase II clinical trial evaluating the efficacy and safety of neoadjuvant becotatug vedotin (an anti-EGFR antibody-drug conjugate) combined with pucotenlimab (HX008, an anti-PD-1 monoclonal antibody) in patients with resectable recurrent head and neck squamous cell carcinoma (rHNSCC) who have progressed on prior PD-1/PD-L1 inhibitor and platinum-based therapy.
A total of 42 EGFR-positive patients will be enrolled using Simon's two-stage design across 11 centers in China (Stage 1: 25 patients; Stage 2: 17 additional patients with 5% dropout). Enrolled patients will receive 3 cycles of neoadjuvant becotatug vedotin (2.3 mg/kg, IV, Q3W) plus pucotenlimab (3 mg/kg, IV, Q3W), followed by salvage surgery (3-4 weeks later), adjuvant radiotherapy +/- chemotherapy per NCCN/CSCO guidelines, and pucotenlimab maintenance therapy (3 mg/kg, Q3W) for up to 12 cycles or until disease progression or unacceptable toxicity.
The primary endpoint is major pathological response (MPR) rate. The null hypothesis MPR rate is 14% (historical data) and the target MPR rate is 30% (alpha=0.05, power=0.8, one-sided). Secondary endpoints include objective response rate (ORR), pathological complete response (pCR), survival outcomes, quality of life, and safety.
详细描述
Recurrent head and neck squamous cell carcinoma (rHNSCC) remains a significant clinical challenge, with recurrence rates of 40-60% after curative treatment. Salvage surgery is the standard of care, yet approximately 50% of patients experience re-recurrence within 2 years. For patients who have progressed on prior PD-1 inhibitor and platinum-based therapy, effective treatment options are extremely limited.
Becotatug vedotin is a novel anti-EGFR antibody-drug conjugate (ADC) that has demonstrated significant anti-tumor activity in HNSCC, with an ORR of 40% in Phase Ia/Ib and 43% in the post-immunotherapy Phase II study. Pucotenlimab (HX008) is a PD-1 inhibitor with an extended half-life (T1/2 = 21.76 days). Phase I/II data showed the combination achieved ORR of 60% in HNSCC with manageable toxicity.
This study investigates neoadjuvant becotatug vedotin plus pucotenlimab in resectable rHNSCC after immunotherapy progression.
TREATMENT REGIMEN:
- Neoadjuvant: Becotatug vedotin 2.3 mg/kg IV + Pucotenlimab 3 mg/kg IV, Q3W, 3 cycles
- Surgery: Salvage surgery 3-4 weeks after neoadjuvant completion
- Adjuvant: IMRT (60-66 Gy/30f) +/- platinum-based chemotherapy per NCCN/CSCO
- Maintenance: Pucotenlimab 3 mg/kg IV Q3W for 12 cycles or until progression/toxicity
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- •Age 18-75 years at time of consent
- •Histologically or cytologically confirmed recurrent head and neck squamous cell carcinoma
- •Disease progression after prior treatment including both PD-1/PD-L1 inhibitor and platinum-based therapy (combined or sequential)
- •EGFR protein expression positive by immunohistochemistry (IHC), with no EGFR-targeted therapy within 6 months prior to enrollment
- •Willing to provide archived tumor tissue or undergo fresh tumor biopsy for EGFR testing
- •At least one measurable extracranial lesion per RECIST v1.1; previously treated lesions must demonstrate clear progression 3 or more months after last local treatment
- •Resectable disease with no distant metastasis, as assessed by a multidisciplinary team
- •Adequate organ function within 7 days prior to enrollment: ANC at least 2.0 x 10^9/L, platelet count at least 100 x 10^9/L; total bilirubin less than 1.5 x ULN, ALT/AST less than 2.5 x ULN; serum creatinine less than 1.5 x ULN
- •Signed informed consent prior to any study-specific procedures
- •Life expectancy greater than 3 months
- •Effective contraception during study and for 6 months after last dose
排除标准
- •History of other malignancies (except cured basal cell carcinoma or cervical carcinoma in situ)
- •Comorbidities requiring long-term immunosuppressive therapy or corticosteroids at immunosuppressive doses
- •Immunodeficiency or history of organ transplantation (including interstitial pneumonia, hepatitis, nephritis, hyperthyroidism, hypothyroidism)
- •HIV/AIDS; untreated active hepatitis B (HBV-DNA at least 500 IU/mL); hepatitis C (HCV-RNA above detection limit); or HBV/HCV co-infection
- •High-dose systemic corticosteroids within 4 weeks prior to enrollment
- •Pregnant or lactating women; fertile patients not using effective contraception
- •Laboratory values not meeting inclusion criteria within 7 days
- •Significantly impaired cardiac, hepatic, pulmonary, renal, or bone marrow function
- •Severe uncontrolled comorbidities or active infections
- •Concurrent participation in other clinical trials
- •Refusal or inability to sign informed consent
- •Other contraindications to study treatment as determined by the investigator
- •Psychiatric disorders or mental illness resulting in lack of legal capacity
研究组 & 干预措施
Neoadjuvant Becotatug Vedotin + Pucotenlimab
干预措施: Becotatug Vedotin (Drug)
Neoadjuvant Becotatug Vedotin + Pucotenlimab
干预措施: Pucotenlimab (Drug)
研究者
Chen Chunyan
Principal Investigator
Sun Yat-sen University