Pre-Operative Pembrolizumab + Chemoradiation in Patients With Locally Advanced Esophageal Squamous Cell Carcinoma

Conditions

Esophageal Squamous Cell Carcinoma

Keywords

Immunotherapy, Pathologic complete response, preoperative pembrolizumab with concurrent chemoradiotherapy, Disease-free Survival, Median overall survival

Brief summary

To investigate the safety and activity of preoperative pembrolizumab combined with chemoradiotherapy for resectable esophageal squamous cell carcinoma (ESCC) ,20 patients enrolled in Phase Ib PALACE-1(NCT03792347).The results showed that preoperative pembrolizumab with concurrent chemoradiotherapy was safe, did not delay surgery and induced a pCR in 55.6% of resected tumors. In this multicentre prospective study(PALACE-2),the investigators will evaluate the efficacy of preoperative pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma.

Detailed description

For locally advanced esophageal squamous cell carcinoma (ESCC), neoadjuvant chemoradiotherapy followed by surgery has been recommended as the optimal therapeutic strategy.Patients who achieved pathologic complete response(pCR) after receiving neoadjuvant therapy were more likely to have better survival. And the pCR rates was 43.2% reported in NEOCRTEC5010 trial, 49% with ESCC in the CROSS trial and 33.3% in FFCD 990130. In Phase Ib PALACE-1(NCT03792347), the investigators firstly present that preoperative pembrolizumab combined with chemoradiotherapy followed by surgery is safe.All 20 patients have received PPCT successfully, except 1 patient who missed the last dose of chemotherapy due to leukopenia. Grade 3 and higher adverse events (AEs) were observed in 13 patients (13/20, 65%), and 1 patient had a grade 5 AE. The most frequent grade 3 AE was lymphopenia (12/13, 92%). Eighteen patients underwent surgery within 4-9 weeks after PPCT and the pCR rate was 55.6% (10/18). This study (PALACE-2) will evaluate the efficacy of preoperative pembrolizumab with concurrent chemoradiotherapy in patients with locally advanced esophageal squamous cell carcinoma in multicentres.

Li C, Han Y, Zhao S, Kang X, Zheng Y, Cao Y, Yan Y, Shi L, Wang X, Lu T, Zou G, Li H, Che J, Xiang J, Zhu L, Hang J, Zhang Y, Jin R, Han D, Chen X, Jing H, Guo W, Cheng Z, Zhao L, Chen X, Yu B, Li J, Li B, Li Y, Li H.

2025-11-28

10.1038/s41392-025-02477-4

A phase II clinical trial of toripalimab combined with neoadjuvant chemoradiotherapy in locally advanced esophageal squamous cell carcinoma (NEOCRTEC1901).

Chen R, Liu Q, Li Q, Zhu Y, Zhao L, Liu S, Chen B, Liu M, Hu Y, Lin T, Li J, Chen J, Lv Y, Fu J, Xi M, Yang H.

2023-07-2628 citations

10.1016/j.eclinm.2023.102118

Role of pretreatment absolute lymphocyte count in survival outcomes for esophageal cancer treated with neoadjuvant chemoradiotherapy and pembrolizumab: An analysis from a prospective cohort.

Wei‐Xiang Qi, Xiaoyan Wang, Jiayi Chen, Shengguang Zhao, Hecheng Li

Journal of Clinical Oncology2023-01-241 citations

10.1200/jco.2023.41.4_suppl.338

Preoperative pembrolizumab combined with chemoradiotherapy for esophageal squamous cell carcinoma: Trial design.

Zheng Y, Li C, Yu B, Zhao S, Li J, Chen X, Li H.

2021-11-1023 citations

10.1016/j.xjon.2021.11.003

Preoperative pembrolizumab combined with chemoradiotherapy for oesophageal squamous cell carcinoma (PALACE-1).

Li C, Zhao S, Zheng Y, Han Y, Chen X, Cheng Z, Wu Y, Feng X, Qi W, Chen K, Xiang J, Li J, Lerut T, Li H.

2020-12-26246 citations

10.1016/j.ejca.2020.11.039

Interventions

DRUGPembrolizumab Injection

Pre-operative Pembrolizumab+chemoradiotherapy

Study design

Allocation

NA

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Masking

NONE

Intervention model description

Participants will receive carboplatin (AUC=2) IV and paclitaxel (50mg/m²) IV on day 1,8,15,22,29. And radiotherapy will start on day 1 of chemotherapy. A total of 41.4 Gy, 23 fractions of 1.8 Gy, 5 fractions a week. Participants will also receive pembrolizumab (2mg/kg) IV on days 1 and 22. Surgery will be performed within 4-6 weeks after completion of preoperative therapy.

Eligibility

Sex/Gender

ALL

Age

18 Years to 75 Years

Healthy volunteers

No

Inclusion criteria

A patient will be eligible for inclusion in this study only if ALL of the following criteria apply: 1. Histologically confirmed cT2-T4a,N0-N+,M0 resectable esophageal squamous cell carcinoma. 2. Eastern Cooperative Oncology Group (ECOG) performance status 0-1 3. Patients approve and sign the informed consent

Exclusion criteria

1. Patients with active autoimmune disease or history of autoimmune disease. 2. Patients who have a condition requiring systemic treatment with either corticosteroids or other immunosuppressive medications. 3. Subjects with a history of symptomatic interstitial lung disease. 4. History of allergy to study drug components. 5. Women must not be pregnant or breast-feeding. 6. Men with female partners (WOCBP) that are not willing to use contraception. 7. Patient has received prior chemotherapy, radiotherapy, target therapy and immune therapy for this malignancy or for any other past malignancy. 8. Underlying medical conditions that, in the Investigator's opinion, will make the administration of study drug hazardous or obscure the interpretation of toxicity or adverse events

Design outcomes

Primary

Measure	Time frame	Description
Pathologic complete response	1 month after resection	Pathologic complete response was defined as pT0N0M0

Secondary

Measure	Time frame	Description
3-year disease free survival	3 years after resection	Percentage of Participants With 3-Year disease-Free Survival (DFS), as Assessed by Response Evaluation Criteria in Solid Tumors (RECIST)1.1. Disease free survival defined as the time from enrollment to the first documented disease progression of local recurrence or distant metastasis or death due to any cause.
Overall Survival (OS)	5 years	OS is defined as the time from enrollment to death due to any cause

Countries

China

Outcome results

None listed