Neoadjuvant Camrelizumab With Dalpiciclib for Resectable Esophageal or Head and Neck Squamous Cell Carcinomas

Head and Neck Squamous Cell Carcinoma Clinical Trial

Official title: The Safety and Feasibility of Neoadjuvant Camrelizumab With Dalpiciclib for the Treatment of Resectable Esophageal or Head and Neck Squamous Cell Carcinoma：A Phase 1 Trial

Status Recruiting

Clinical Trial Summary

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 esophageal squamous cell carcinoma (ESCC) or or head and neck squamous cell carcinoma(HNSCC).

Clinical Trial Description

Esophageal cancer is the seventh leading cause of cancer related mortality worldwide and esophagus squamous cell carcinoma (ESCC) is the main histological type in China. Combination with operation and neoadjuvant therapy including chemotherapy with/without radiotherapy is considered the standard therapy for local advanced esophagus cancer. Nevertheless, in a phase 3 clinical trial，the 5-year overall survival rate and cumulative incidence of recurrence were 59.9% and 32.2%. It shows the limitations of current treatment modalities.

Immunotherapy such as PD-1/PD-L1 inhibitors have shown great improvement in first-line recurrent/metastatic and postoperative ESCC. It motivates recent phase I/II trials investigating the incorporation of ICB in the neoadjuvant treatment of ESCC.

However, a phase 1b trial of neoadjuvant adebrelimab in locally advanced resectable ESCC showed only 24% major pathologic response (MPR; tumor regression >90%). To improve the efficacy of ICB in neoadjuvant treatment of ESCC, a combined regimen should be explored.

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 ESCC and HNSCC. It will also provide new ideas, strategies, and experimental evidence for the development of immunotherapy. ;

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Squamous Cell
• Esophageal Squamous Cell Carcinoma
• Head and Neck Squamous Cell Carcinoma
• Squamous Cell Carcinoma of Head and Neck

• NCT number: NCT06109207
• Study type: Interventional
• Source: West China Hospital
• Contact: Jin Zhou, MD.,PhD.
• Phone: +8613880626596
• Email: zhoujin096@scu.edu.cn
• Status: Recruiting
• Phase: Phase 1
• Start date: October 31, 2023
• Completion date: October 31, 2025