Camrelizumab, Chemotherapy and Ivarmacitinib in Patients With Resectable Esophageal Squamous Cell Carcinoma

A Prospective, Single-arm, Single-center, Exploratory Study of the Safety and Efficacy of the Combination of Camrelizumab, Chemotherapy and Ivarmacitinib in Patients With Resectable Esophageal Squamous Cell Carcinoma

In the management of locally advanced esophageal squamous cell carcinoma, the outcomes associated with surgical resection, whether conducted alone or supplemented with postoperative adjuvant radiotherapy and chemotherapy, have been suboptimal. Immune checkpoint inhibitors (ICIs) have shown potential in enhancing the immune system's capacity to target and eliminate cancer cells. Evidence suggests that the concurrent administration of JAK inhibitors with ICIs may improve anti-cancer efficacy, increase patient response rates, and prolong progression-free survival compared to ICIs alone. This prospective, exploratory study aims to assess the efficacy of combining camrelizumab, chemotherapy, and Ivarmacitinib in neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma, with the objective of broadening therapeutic options for this malignancy.

Study Overview

• Status: Not yet recruiting
• Conditions: Neoadjuvant Therapy; Esophageal Squamous Cell Carcinoma
• Intervention / Treatment: Combination product: Camrelizumab, Chemotherapy and Ivarmacitinib; Procedure: Esophagectomy; Other: Sample

Detailed Description

In the management of locally advanced esophageal squamous cell carcinoma, the outcomes associated with surgical resection, whether conducted alone or supplemented with postoperative adjuvant radiotherapy and chemotherapy, have been suboptimal. The high risk of local recurrence and distant metastasis, which affect patient prognosis and survival rates. Preoperative immunotherapy holds the potential to activate the patient's immune system to recognize tumor antigens and establish immune memory, thereby enabling the immune system to maintain its surveillance role following surgical tumor resection. Consequently, there is a growing emphasis on the administration of immunotherapy prior to surgery across various solid tumor types.

Immune checkpoint inhibitors (ICIs) have shown potential in enhancing the immune system's capacity to target and eliminate cancer cells. However, a substantial subset of patients either responds inadequately or develops resistance to these therapies. To address this challenge, numerous combination treatment strategies have been explored in clinical research. Evidence suggests that the concurrent administration of JAK inhibitors with ICIs may improve anti-cancer efficacy, increase patient response rates, and prolong progression-free survival compared to ICIs alone. Notably, there is a paucity of research regarding the combination of camrelizumab with chemotherapy and Ivarmacitinib as a neoadjuvant therapy. This prospective, exploratory study aims to assess the efficacy of combining camrelizumab, chemotherapy, and Ivarmacitinib in neoadjuvant treatment for locally advanced esophageal squamous cell carcinoma, with the objective of broadening therapeutic options for this malignancy.

• Study Type: Interventional
• Enrollment (Estimated): 45
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Zixiang Wu, M.D; Phone Number: +8615268156132; Email: zixiang0717@zju.edu.cn

Study Locations

• China
  • China
    • Hangzhou, China, China, 310009
      • 2nd Affiliated Hospital, School of Medicine, Zhejiang University
      • Contact: Ming Wu, M.D; Phone Number: +8613757118715; Email: iwuming22@zju.edu.cn
      • Contact: Hong Shen, M.D; Phone Number: +8613362891320; Email: shenhong0023@zju.edu.cn

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. signed informed consent;
2. patients age 18 to 75 years old
3. primary resectable, histologically confirmed esophageal squamous cell cancer;
4. Esophageal squamous cell carcinoma the clinical stage was II-IVA (according to AJCC TNM stage, 8th edition).
5. ECOG PS 0-1.
6. No distant metastasis, the diseases could be resectable assessed by thoracic oncologist．

Exclusion Criteria:

1. with significant cardiovascular disease;
2. current treatment with anti-viral therapy or HBV;
3. Female patients who are pregnant or lactating;
4. history of malignancy within 5 years prior to screening;
5. active or history of autoimmune disease or immune deficiency;
6. signs of distant metastases.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Camrelizumab, Chemotherapy and Ivarmacitinib; The preoperative neoadjuvant therapy consists of 3 cycles, each with a duration of 21 days. Ivarmacitinib tablets are administered orally at a dosage of 4 mg daily during the first and second cycles, but are omitted during the third cycle. Radical surgery is scheduled to occur between 4 to 8 weeks after the final dose of the neoadjuvant therapy. The requirement for postoperative radiotherapy is evaluated based on the patient's clinical condition and pathological stage. Camrelizumab maintenance therapy may be extended for up to 1 year. Throughout the study, patients are monitored until the occurrence of disease progression, withdrawal of informed consent, loss to follow-up, or death.

Combination product: Camrelizumab, Chemotherapy and Ivarmacitinib; The treatment regimen includes the administration of Camrelizumab at a dose of 200 mg, Paclitaxel (albumin-bound) at 260 mg/m², and Carboplatin with an area under the curve (AUC) of 5. These medications are administered every 3 weeks for a total of 3 cycles. Additionally, Ivarmacitinib tablets are administered orally at a dosage of 4 mg daily during the first and second cycles, but are omitted during the third cycle, totaling 42 days of administration.; Procedure: Esophagectomy; Prior to each surgical procedure, the department engaged in comprehensive discussions to determine and establish the most appropriate course of action. Depending on the tumor location, a minimally invasive Ivor-Lewis (intrathoracic anastomosis) or McKeown (neck anastomosis) esophagectomy, including two-field extensive lymphadenectomies, was performed. The resection length was required to be at least 5 cm from the tumor origin, as determined by pre-chemotherapy endoscopy. These surgeries were conducted by surgeons with extensive experience. Minimally invasive esophagectomy could be performed using the da Vinci surgical robot, thoracoscope, or laparoscope, or through an open approach, as deemed appropriate by the surgeon.; Other: Sample; Blood, Tumour will be Collected from participant. Fate of sample is Destruction after use. 5 ml of peripheral blood was collected the day before each of the immunotherapy sessions and after surgery. Tumour sample will be collected before neoadjuvant therapy and during surgery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of pathological complete response (PCR)	The proportion of the surgical population with PCR, which was defined no residual invasive tumor cells were found in the pathological examination of resected specimens, including the primary tumor and lymph nodes.	1 month after surgery

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of Treatment-related Adverse Events	Incidence of Treatment-related Adverse Events as Assessed by CTCAE v5.0	1 month after surgery
Rate of major pathological response (MPR)	The proportion of the surgical population with MPR, which was defined in the pathological examination of resected specimens, the proportion of residual tumor cells was less than 10%.	1 month after surgery
Rate of objective response rate (ORR)	The proportion of subjects with imaging PR or CR assessed according to RECIST 1.1 criteria	before surgery]
2-year and 5-year event free survival (EFS)	The proportion of study cases from the time of enrollment to either the occurrence of disease recurrence or death from any cause, whichever occurred first, was analyzed within both 2-year and 5-year intervals.	2-year and 5-year after enrolled
The changes in the peripheral blood immunoprofile and tumor tissue sample among non-PCR (NPCR) and PCR patients	By using mass spectrometry (CyTOF), single-cell analysis, and other detecting techniques , we comprehensively characterized the immune landscape in the peripheral blood and tumor sample of ESCC patients before and after anti- PD-1 immunotherapy, aiming to explore the immune subsets correlated with neoadjuvant immunotherapy response.	3 month after surgery

Collaborators and Investigators

• Sponsor: Second Affiliated Hospital, School of Medicine, Zhejiang University
• Investigators: Study Chair: Jianan Wang, 2nd Affiliated Hospital, School of Medicine, Zhejiang University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2026
• Primary Completion (Estimated): December 31, 2028
• Study Completion (Estimated): December 31, 2033

Study Registration Dates

• First Submitted: March 26, 2026
• First Submitted That Met QC Criteria: March 26, 2026
• First Posted (Actual): April 1, 2026

Study Record Updates

• Last Update Posted (Actual): April 1, 2026
• Last Update Submitted That Met QC Criteria: March 26, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: Camrelizumab; Ivarmacitinib
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Head and Neck Neoplasms; Neoplasms, Glandular and Epithelial; Esophageal Diseases; Carcinoma; Neoplasms, Squamous Cell; Carcinoma, Squamous Cell; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Therapeutics; Surgical Procedures, Operative; Digestive System Surgical Procedures; Drug Therapy; camrelizumab; Esophagectomy; ivarmacitinib
• Other Study ID Numbers: 2026-0379

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No