A Phase II, Single Arm Study Investigating Neoadjuvant Plus Adjuvant Treatment with Cemiplimab in High Risk, Surgically Resectable, Stage III Cutaneaous Squamous Cell Carcinoma
试验速览
- 阶段
- 2 期
- 状态
- 进行中（未招募）
- 发起方
- 入组人数
- 25
- 试验地点
- 7
- 主要终点
- Major pathological response rate
研究概览
简要总结
Neoadjuvant plus adjuvant treatment with immunotherapy may have an anti-tumor activity and reduce the risk of relapse in patients with high risk surgically resectable stage III cutaneous squamous cell carcinoma.
详细描述
Cutaneous squamous cell carcinoma (CSCC) is the second most common skin cancer in US. It is associated with a surgical cure rate >95% in early stage disease but a small percentage of patients develop unresectable locally advanced or metastatic CSCC. The 2018 FDA approval of Libtayo was based on a combined analysis of data from an open-label, multi-center, non-randomized Phase 2 trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced CSCC expansion cohorts from a multi-center, open-label, non-randomized Phase 1 trial (Study 1423). Conventional cytotoxic chemotherapy can induce tumor responses but is often poorly tolerated, specially among older patients with CSCC. CSCC has higher mutation burden than any tumor type and immunosuppression is a known risk factor. Furthermore, PD-L1 expression has been associated with high risk disease1 suggesting that CSCC may be responsive to PD-1 checkpoint blockade.
Cemiplimab is a human anti-PD-1 monoclonal antibody, under study for patients with unresectable locally advanced and/or regionally or metastatic CSCC. It has been studied in a phase I dose escalation, where a durable radiologic complete response was achieved in CSCC patients.2-3 In this study, the partial response was 25% in locally advanced and 60% in metastatic CSCC,stable disease was 31.3% in locally advanced and 10% in metastatic CSCC, progressive disease was 25% in locally advanced and 20% in metastatic CSCC with an overall response rate of 46.2% and a disease control rate of 69.2%. The 2018 FDA approval of Libtayo was based on a combined analysis of data from an open-label, multi-center, non-randomized Phase 2 trial known as EMPOWER-CSCC-1 (Study 1540) and two advanced CSCC expansion cohorts from a multi-center, open-label, non-randomized Phase 1 trial (Study 1423). Together, the trials represent the largest prospective data set in advanced CSCC. The major efficacy outcome measures for the integrated analysis of EMPOWER-CSCC-1 and the two CSCC expansion cohorts were confirmed objective response rate (ORR), as assessed by independent central review (ICR), and ICR-assessed duration of response (DOR).
Across the entire population, the overall response rate (ORR) at a median follow-up of 8.9 months was 47% (95% CI, 38-47). The complete response (CR) rate was 4% and the partial response (PR) rate was 44%. The duration of response ranged from 1 month to over 15 months. Sixty-one percent of patients had a duration of response ≥6 months.
Among 75 patients with metastatic CSCC, the ORR was 47% (95% CI, 35-59). The CR rate was 5% and the PR rate was 41%. The duration of response ranged from 3 months to over 15 months. Sixty percent of patients had a duration of response ≥6 months. In the 33 patients with locally advanced disease, the ORR was 49% (95% CI, 31-67), comprising all PRs. The duration of response ranged from 1 month to over 13 months. Sixty-three percent of patients had a duration of response ≥6 months.
Cemiplimab therefore produced rapid, deep and durable tumor reductions in target lesions.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Patients of either sex aged ≥18 years.
- •Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
- •Patients must have histologically or cytologically confrimed stage III cutaneous squamous cell carcinomas. The definition of resectability can be determined by the patient's surgical oncologist and verified via discussion at Multidisciplinary Tumor Conference attended by CSCC medical and surgical oncology staff. Resectable tumors are defined as having no significant vascular, neural or bony involvement.
- •Patients must be medically fit enough to undergo surgery as determined by the surgical oncology team.
- •Patients must have measurable disease, defined by Response Evaluation Criteria In Solid Tumors (RECIST) 1.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Patients must have organ and marrow function
- •Female subjects of childbearing potential must have a negative pregnancy test result at baseline and must practice a reliable method of contraception for the total study duration plus 16 weeks (i.e., 30 days plus the time required for cemiplimab to undergo five half lives) after the last dose of cemiplimab.
- •Men who are sexually active with women of childbearing potential must practice a reliable method of contraception for the total study duration plus 16 weeks (i.e., 80 days plus the time required for cemiplimab to undergo five half-lives) after the last dose of cemiplimab.
排除标准
- •Evidence of metastatic disease extra lymphnodal.
- •Currently and previous cancer therapy (chemotherapy, radiation therapy, immunotherapy, or biologic therapy) or investigational anti-cancer drug.
- •Prior malignancy within the prior 5 years, except for the following: in-situ cervical cancer, thyroid cancer (except anaplastic) or any cancer from which the patient has been disease-free for 2 years.
- •Any major surgery within the last 3 weeks.
- •Unwillingness or inability to follow the procedures required in the protocol.
- •Uncontrolled diabetes, hypertension, pneumonitis and abnormal thyroid function or other medical conditions that may interfere with assessment of toxicity.
- •Subjects with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of treatment.
- •Female subjects who are pregnant (positive pregnancy test), breast-feeding, or who are of childbearing potential and not practicing a reliable method of birth control.
- •Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection;
- •Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
研究组 & 干预措施
single arm
Patients will receive cemiplimab at a dosage of 350 mg every 3 weeks for two cycles prior surgery. Stage III stage must be documented at screening and re-assessed prior surgery by spiral or multidetector computed tomography (CT) scan (if clinically indicated) and Positron emission tomography (PET). Postoperatively, adjuvant immunotherapy with cemiplimab will be administered at a dosage of 350 mg every 3 weeks for one year.
干预措施: Cemiplimab (Drug)
结局指标
主要结局
Major pathological response rate
时间窗: 43-71 days
\<10% remaining viable tumour cells in resected primary tumor
次要结局
- Use of selected biomarkers to detect molecular and immunophenotypic changes(At screening 1 and 2, at surgery, every 12 weeks during adjuvant and at recurrence of disease untill an average of 1 year from surgery)
- Recurrence-free survival(At 6 and 12 months postoperative)
- Overall Survival(Until three years from last infusion)
- Prevalence of related AEs(Through study treatment completion, an average of 17 months)