The Safety and Feasibility of Neoadjuvant Camrelizumab With Dalpiciclib for the Treatment of Resectable Head and Neck Squamous Cell Carcinoma：A Phase 1 Trial
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 6
- 试验地点
- 1
- 主要终点
- Safety of combination camrelizumab and dalpiciclib as assessed by number of participants who experience adverse events
研究概览
简要总结
The purpose of this study is to explore the safety and feasibility of anti-programmed cell death protein 1(PD-1) immunotherapy, Camrelizumab, combined with cyclin-dependent kinase 4/6 blockade, Dalpiciclib, as a new neoadjuvant treatment regimen for patients with resectable head and neck squamous cell carcinoma(HNSCC).
详细描述
Head and Neck Squamous Cell Carcinoma (HNSCC) is the most common malignancies of the head and neck, accounting for 90% of head and neck cancer. The 5-year survival rate under standard treatment is only 50%. 70%~80% of first diagnosed patients already developed into locally advanced status (stage II-Iva). In recent years, the use of neoadjuvant therapy (NAC) followed by surgery or radiotherapy has been advocated because of its higher probability of local/regional failure and distant metastasis after treatment. TPF (Docetaxel + Cisplatin + Fluorouracil) regimen is considered as the standard regimen of induced chemotherapy for head and neck squamous cell carcinoma (especially in laryngeal cancer), which can significantly reduce the patient's distant metastasis rate and prolong overall survival (OS). However, the therapeutic effect of neoadjuvant therapy on head and neck squamous cell carcinoma has reached a bottleneck. In recent years, PD-1 inhibitors have achieved significant effects in the field of tumor therapy and have been approved for the treatment of various tumors including recurrent metastatic head and neck tumors. There are also several prospective clinical research attempting to combine ICB with targeted therapeutic drugs for neoadjuvant therapy of HNSCC. The efficacy and safety results show potential synergy between these drugs.
Recent preclinical studies have shown that CDK4/6 inhibitors promote efficacy of PD-1/PD-L1 inhibitors through tumor antigen presentation enhancing, suppressed proliferation of regulatory T (Treg) cells, effector T- cell activation enhancing, and induction of T- cell memory. The previous study confirmed that CDK4/6 inhibitor combined with ICB can be administered safely in patients with recurrent or metastatic head and neck squamous cell carcinoma(HNSCC) and non-small cell lung carcinoma(NSCC).
In summary, the investigators designed this study to explore the safety and efficacy of anti-PD1 immunotherapy, Camrelizumab, combined with CDK4/6 inhibitor, dalpiciclib, as a new neoadjuvant treatment regimen for patients with resectable HNSCC. It will also provide new ideas, strategies, and experimental evidence for the development of immunotherapy.
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Sequential
- 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
- •Age 18 years or above.
- •Patients with pathologically confirmed HNSCC (except for nasopharyngeal carcinoma) and meet the following conditions:
- •were newly diagnosed and without distant metastasis;
- •were deemed surgically resectable evaluated by a head and neck surgeon;
- •were willing to undergo surgery.
- •Eastern Cooperative Oncology Group (ECOG) performance status 0-
- •Adequate organ and bone marrow function: absolute neutrophil count ≥ 1.5 × 10^9/L, hemoglobin ≥ 80 g/L, platelets ≥ 80 × 10^9/L;ALT, AST and ALP < 2.5× upper limit of normal (ULN), total bilirubin ≤ 2×ULN;albumin≥ 2.8 g/dL；creatinine clearance ≥ 60 ml/min；INR≤ 1.5；APTT≤ 1.5×ULN
- •Written informed consent.
排除标准
- •History of other malignancies (except for the history of malignant tumors that have been cured and have not recurred within 5 years, such as skin basal cell carcinoma, skin squamous cell carcinoma, superficial bladder cancer, in situ cervical cancer, and gastrointestinal mucosal cancer, etc.）
- •Have an active autoimmune disease requiring systemic treatment or a documented history of clinically severe autoimmune disease.
- •Any history of allergic disease, or a sever hypersensitivity reaction to drugs, or allergy to the study drug components.
- •Any of prior therapy with:anti-PD-1, anti-PD-L1/2, anti-CTLA-4 antibody, anti-EGFR antibody or EGFR-TKIs； antitumor vaccine; any active vaccine against an infectious disease within 4 weeks prior to the first dose or planned during the study period; major surgery or serious trauma within 4 weeks before the first dose; toxicity from prior antitumor therapy has not recovered to ≤ CTCAE Version 5.0 ·Grade 1 or the level specified by the inclusion/exclusion criteria.
- •With serious medical diseases, such as grade II and above cardiac dysfunction (NYHA criteria), ischemic heart disease, supraventricular or ventricular arrhythmia, poorly controlled diabetes mellitus, poorly controlled hypertension, echocardiographic ejection fraction < 50%, etc.
- •With interstitial pneumonitis, non-infectious pneumonitis, active pulmonary tuberculosis, or history of pulmonary tuberculosis infection that were not controlled by treatment.
- •With hyperthyroidism, or organic thyroid disease.
- •With active infection, or unexplained fever during the screening period or 48 hours before the first dose.
- •With active hepatitis B or C, or known history of positive HIV test, or acquired immunodeficiency syndrome.
- •History of a clear neurological or psychiatric disorder.
- •History of drug abuse or alcohol abuse.
- •Women who are pregnant or breastfeeding, or have a reproductive plan from the screening period to 3 months after the end of the study, or have sex without contraceptive measures, or are unwilling to take appropriate contraceptive measures.
- •Received any investigational drug within 4 weeks prior to the first dose, or concurrently enrolled in another clinical trial.
- •Any other factors that are not suitable for inclusion in this study judged by investigators.
研究组 & 干预措施
Camrelizumab+Dalpiciclib(100mg) 3 patients
Camrelizumab will be given at at a dose of 200 mg intravenously every three weeks on day 1 of a planned 21-day cycle, and two doses before surgery
Dalpiciclib will be given at a dose of 100 mg every day orally with three weeks on and one week off. Four weeks is a cycle and it will be given for two cycles.
For dalpiciclib, there is 2 dose levels, 100mg qd and 150 mg qd, and if no patients experience DLT on 100mg level, 150mg level will be administered.
干预措施: Camrelizumab (Drug)
Camrelizumab+Dalpiciclib(100mg) 3 patients
Camrelizumab will be given at at a dose of 200 mg intravenously every three weeks on day 1 of a planned 21-day cycle, and two doses before surgery
Dalpiciclib will be given at a dose of 100 mg every day orally with three weeks on and one week off. Four weeks is a cycle and it will be given for two cycles.
For dalpiciclib, there is 2 dose levels, 100mg qd and 150 mg qd, and if no patients experience DLT on 100mg level, 150mg level will be administered.
干预措施: Dalpiciclib 100mg (Drug)
Camrelizumab+Dalpiciclib(150mg) 3 patients
Camrelizumab will be given at at a dose of 200 mg intravenously every three weeks on day 1 of a planned 21-day cycle, and two doses before surgery
Dalpiciclib will be given at a dose of 150 mg every day orally with three weeks on and one week off. Four weeks is a cycle and it will be given for two cycles.
For dalpiciclib, there is 2 dose levels, 100mg qd and 150 mg qd, and if no patients experience DLT on 100mg level, 150mg level will be administered.
干预措施: Camrelizumab (Drug)
Camrelizumab+Dalpiciclib(150mg) 3 patients
Camrelizumab will be given at at a dose of 200 mg intravenously every three weeks on day 1 of a planned 21-day cycle, and two doses before surgery
Dalpiciclib will be given at a dose of 150 mg every day orally with three weeks on and one week off. Four weeks is a cycle and it will be given for two cycles.
For dalpiciclib, there is 2 dose levels, 100mg qd and 150 mg qd, and if no patients experience DLT on 100mg level, 150mg level will be administered.
干预措施: Dalpiciclib 150mg (Drug)
结局指标
主要结局
Safety of combination camrelizumab and dalpiciclib as assessed by number of participants who experience adverse events
时间窗: Through the study completion, an average of 12 weeks
Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
Feasibility of combination camrelizumab and dalpiciclib as assessed by number of participants who experience adverse events
时间窗: Through the study completion, an average of 12 weeks
Number of participants who experience grade 1 or higher adverse events, as defined by Common Terminology Criteria for Adverse Events version 5.0 (CTCAE v5.0).
次要结局
- Overall survival (OS)(Up to 2 years)
- Maximum Tolerated Dose (MTD) as determined by number of participants with dose limiting toxicities (DLT)(Through the study completion, an average of 12 weeks)
- Major Pathologic Response(Time of surgery)
- Objective response rate (ORR)(Through the study completion, an average of 12 weeks)
- Progression free survival(PFS)(Up to 2 years)
研究者
Xingchen Peng
professor
West China Hospital