Pucotenlimab (HX008) Combined With Becotatug Vedotin (MRG003) as Neoadjuvant Therapy for Locally Advanced Penile Squamous Cell Carcinoma：A Multicenter, Single-Arm, 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
- 29
- 试验地点
- 1
- 主要终点
- Pathological Complete Remission (pCR) Rate
研究概览
简要总结
This is an open-label, multicenter, single-arm Phase 2 clinical trial evaluating neoadjuvant pucotenlimab (anti-PD-1 immunotherapy) combined with becotatug vedotin (EGFR-targeted antibody-drug conjugate, ADC) for adults with locally advanced penile squamous cell carcinoma. Eligible patients have high-risk disease defined as T4 primary tumor with any nodal status or any T stage with N2-N3 lymph node metastasis and no distant metastasis.
All participants receive up to 4 cycles of combination neoadjuvant therapy every 3 weeks. After treatment completion, a multidisciplinary team will assess if consolidative surgery can be performed. Patients who undergo surgery will continue single-agent pucotenlimab adjuvant treatment for 17 additional cycles (approximately 1 year).
The primary goal is to measure the pathological complete response (pCR) rate. Secondary goals include objective response rate (ORR), progression-free survival (PFS),overall survival (OS) and safty profiles. Blood and tumor tissue samples will be collected to explore biomarkers that may predict treatment response and drug resistance. A total of 29 male patients will be enrolled.
详细描述
Background:
Penile squamous cell carcinoma is a rare genitourinary malignancy with poor outcomes once regional lymph node spread occurs. Up to 45% of patients present with nodal metastasis at initial diagnosis. Patients with pelvic lymph node involvement (N3) have a 0-17% 5-year survival rate, and 86% of locally advanced patients experience recurrence within 2 years after standard surgery alone. The guidelines recommended neoadjuvant chemotherapy regimen (paclitaxel, ifosfamide, cisplatin, TIP) yields only a 10% pathological complete response rate, with limited long-term disease control and short survival after disease progression.
Over 90% of penile squamous cell carcinomas overexpress EGFR, and 40%-60% of patients show PD-L1 positivity, supporting dual targeting of EGFR and PD-1 as a promising therapeutic strategy. Preclinical and early clinical data confirm synergistic anti-tumor activity between EGFR ADCs and PD-1 inhibitors: the ADC payload promotes dendritic cell maturation and antigen presentation, while PD-1 blockade restores anti-tumor T cell function. Previous prospective trials demonstrate that this combination produces meaningful tumor regression and survival outcomes in other squamous cell carcinomas, with manageable toxicities.
This trial adopts a Simon two-stage single-arm design to efficiently test the study regimen's anti-tumor activity without a separate control group. If the first 10 enrolled patients show minimal pathological response, the trial will stop early for futility; otherwise, enrollment will continue to a total of 29 subjects to generate robust efficacy and safety data for this chemotherapy-free neoadjuvant platform.
Safety Oversight:
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
- Male
- 接受健康志愿者
- 否
入选标准
- •Aged 18-75 years, biologically male.
- •Histologically confirmed penile squamous cell carcinoma, stage T4 any N M0 or any T N2-N3 M0 without distant metastasis.
- •Treatment-naive; or relapsed patients with ≥12 months interval from last prior systemic therapy.
- •At least one measurable target lesion per RECIST 1.
- •ECOG performance status 0-
- •Adequate bone marrow, liver and renal function as predefined lab thresholds.
- •Expected survival ≥12 months.
- •No severe uncontrolled organ dysfunction.
- •Able to understand and voluntarily sign written informed consent.
排除标准
- •Pre-existing grade ≥2 peripheral neuropathy interfering daily activities.
- •Prior neoadjuvant therapy for penile cancer; previous use of PD-1/PD-L1 inhibitors or EGFR ADCs including becotatug vedotin.
- •Known hypersensitivity to pucotenlimab, becotatug vedotin or excipients.
- •Active malignancy within 5 years (excluding cured basal cell skin carcinoma and low-risk prostate cancer).
- •Uncontrolled severe cardiovascular disease, active hepatitis B/C, active infection requiring antibiotics within 2 weeks before enrollment.
- •Live vaccine administered within 30 days before first dosing.
- •HIV infection, autoimmune disease requiring systemic therapy within 2 years, long-term systemic immunosuppressants.
- •Other conditions judged by investigators to interfere with study treatment or assessment.
研究组 & 干预措施
Treatment
Single arm: Neoadjuvant pucotenlimab + becotatug vedotin, then adjuvant pucotenlimab for surgical patients.
Max 4 neoadjuvant cycles (Q3W): Day1 pucotenlimab 3mg/kg (max 200mg, 60min IV), ≥30min later becotatug vedotin 2.0mg/kg (60-90min IV). Therapy stops early for progression/unmanageable toxicity.
Post-neoadjuvant MDT assessment for consolidative surgery. Resectable patients receive 17 cycles of adjuvant pucotenlimab 200mg Q3W.
干预措施: Pucotenlimab plus Becotatug Vedotin (Drug)
结局指标
主要结局
Pathological Complete Remission (pCR) Rate
时间窗: Within 4 weeks after consolidative surgery
Percentage of patients achieving pathological complete remission, defined as no residual invasive tumor cells in primary penile lesion and resected regional lymph nodes after neoadjuvant therapy and consolidative surgery.
次要结局
- Objective Response Rate (ORR)(Evaluation at the end of Cycle 2 or 4 (each cycle is 21 days) of neoadjuvant treatment)
- Progression-Free Survival (PFS)(From the date of study enrollment until the date of first documented tumor progression or death from any cause (whichever occurs first), assessed up to 12 months)
- Overall Survival (OS)(From the date of study enrollment to death from any cause, assessed up to 12 months)
- Incidence of Treatment-Related Adverse Events (TRAEs)(From enrollment to 28 days after last study treatment)
研究者
ZHOU FANGJIAN
M.D., Ph.D.
Sun Yat-sen University