Trial Title:
BTLA Inhibitor (JS004) Combined with Toripalimab and Chemotherapy in the Perioperative Treatment of Resectable Locally Advanced Thoracic Esophageal Squamous Cell Carcinoma
NCT ID:
NCT06588335
Condition:
Esophageal Squamous Cell Carcinoma
Conditions: Official terms:
Carcinoma
Carcinoma, Squamous Cell
Esophageal Squamous Cell Carcinoma
Paclitaxel
Cisplatin
Study type:
Interventional
Study phase:
Phase 2
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
BTLA inhibitor (JS004)
Description:
BTLA inhibitor (JS004):200mg, intravenous infusion , d1, Q3W;
Arm group label:
S004+ Toripalimb+Chemotherapy (paclitaxel + cisplatin)
Intervention type:
Drug
Intervention name:
Toripalimab
Description:
Toripalimab:240mg,intravenous infusion, d1, Q3W;
Arm group label:
S004+ Toripalimb+Chemotherapy (paclitaxel + cisplatin)
Intervention type:
Drug
Intervention name:
Paclitaxel, Cisplatin
Description:
Paclitaxel, 175mg/m2, intravenous infusion, d1, Q3W; Cisplatin, 75mg/m2, intravenous
infusion, d1, Q3W;
Arm group label:
S004+ Toripalimb+Chemotherapy (paclitaxel + cisplatin)
Summary:
This is a single-center, single-arm, phase II study, aiming to preliminarily explore the
efficacy and safety of JS004 combined with toripalimab and chemotherapy for perioperative
treatment of locally advanced thoracic esophageal squamous cell carcinoma that is
resectable. The plan is to enroll 20 patients with locally advanced resectable thoracic
esophageal cancer. In the neoadjuvant treatment phase, patients will receive JS004 +
toripalimab + chemotherapy (paclitaxel + cisplatin) for 2 cycles. This will be followed
by the surgical phase: surgery will be performed 3-8 weeks after the last dose of
neoadjuvant treatment. In the postoperative maintenance treatment phase, maintenance
treatment will start 4 weeks ± 7 days after surgery, but no later than 10 weeks after
surgery. For patients with R0 resection confirmed by postoperative pathology, they will
receive maintenance treatment with JS004 + toripalimab for up to 15 cycles. For patients
with non-R0 resection, they will receive maintenance treatment with JS004 + toripalimab
combined with standard radiation or chemotherapy (selected by the investigator based on
esophageal cancer guidelines). During the study, the maximum number of cycles of JS004
combined with toripalimab is 17 cycles (approximately 1 year).
Criteria for eligibility:
Criteria:
Inclusion Criteria:
1. The patient voluntarily participates in this study, signs the informed consent form,
has good compliance, and cooperates with the follow-up;
2. Age 18-75 years old, including 18 and 75 years old, both male and female;
3. Histologically or cytologically confirmed clinical stage of locally advanced
(T1N1-3M0 or T2-3N0-3M0) thoracic esophageal squamous cell carcinoma (8th UICC-TNM
staging);
4. Enhanced CT of the neck shows no suspicious metastatic lymph nodes (excluding lymph
nodes in the esophageal cancer area), and imaging examination shows no distant
metastasis;
5. ECOG: 0~1 score;
6. Expected to achieve R0 resection;
7. No previous anti-tumor treatment for esophageal cancer, including chemotherapy,
radiotherapy (including planned radiotherapy during the study period), hormone
therapy and immunotherapy;
8. Have measurable lesions or assessable non-measurable lesions (according to RECIST
1.1 criteria);
9. The function of important organs meets the following requirements (no use of any
blood components and cell growth factors is allowed within 2 weeks before the
screening examination): a. Absolute neutrophil count (ANC) ≥1.5×10^9/L; b. Platelets
≥100×10^9/L; c. Hemoglobin ≥90g/dL; d. Serum albumin ≥2.8g/dL; e. Total bilirubin
≤1.5×ULN, ALT, AST and/or AKP ≤2.5×ULN; f. Serum creatinine ≤1.5×ULN or creatinine
clearance ≥60mL/min (calculated by Cockcroft-Gault formula); g. International
Normalized Ratio (INR) and Activated Partial Thromboplastin Time (APTT) ≤1.5×ULN
(for those using a stable dose of anticoagulant therapy such as low molecular weight
heparin or warfarin, and the INR is within the expected therapeutic range of the
anticoagulant, they can be screened);
10. For female subjects of childbearing potential, a urine or serum pregnancy test must
be performed within 72 hours prior to receiving the first study drug, and the result
must be negative, and they are willing to use effective contraception during the
study period and for 6 months after the last dose.
Exclusion Criteria:
1. Patients at high risk of gastrointestinal bleeding, esophageal fistula, or
esophageal perforation.
2. Patients with uncontrolled, recurrent pleural effusion, pericardial effusion, or
ascites requiring repeated drainage.
3. Patients with severe dysfunction of the heart, lung, liver, kidney, hematopoietic
system, endocrine system, or cachexia.
4. Patients who have received any of the following treatments: a. Major surgery (except
for diagnostic tissue biopsy) or serious trauma within 4 weeks prior to first study
drug administration. b. Anti-cancer therapy (including chemotherapy, radiotherapy,
immunotherapy, targeted therapy, biotherapy, or tumor embolization) within 4 weeks
prior to first study drug administration. c. Any investigational drug within 4 weeks
prior to first study drug administration. d. Anti-cancer vaccine or live vaccine
within 4 weeks prior to first study drug administration. e. Systemic corticosteroid
therapy (>10 mg prednisone equivalent per day) or other immunosuppressants within 2
weeks prior to first study drug administration, except for local inflammation of the
esophagus and prevention of allergy and nausea/vomiting.
5. Patients whose previous anti-cancer therapy toxicity has not recovered to ≤CTCAE
Grade 1 (except for alopecia).
6. Patients with sodium, potassium, or calcium laboratory abnormalities >Grade 1 that
cannot be corrected within 2 weeks prior to first study drug administration.
7. Patients with any active autoimmune disease or history of autoimmune disease (e.g.,
interstitial pneumonitis, uveitis, colitis, hepatitis, hypophysitis, vasculitis,
myocarditis, nephritis, hyperthyroidism, hypothyroidism), except for vitiligo or
childhood asthma/allergy that has resolved without the need for intervention in
adulthood.
8. Patients with a history of immunodeficiency, including HIV-positive, other acquired
or congenital immunodeficiency disorders, organ transplant, or allogeneic bone
marrow transplant.
9. Patients with uncontrolled cardiac conditions, such as (1) NYHA Class II or higher
heart failure, (2) unstable angina, (3) myocardial infarction within 1 year, or (4)
clinically significant arrhythmias requiring intervention.
10. Patients with a serious infection (CTCAE >Grade 2) within 4 weeks prior to first
study drug administration, active lung inflammation on baseline imaging, or
symptoms/signs of infection within 2 weeks prior to first study drug administration
requiring oral or IV antibiotics (except for prophylactic use).
11. Patients with active hepatitis B (HBV DNA ≥ 2000 IU/mL or 104 copies/mL) or active
hepatitis C (positive HCV antibody and detectable HCV-RNA).
12. Patients with known hypersensitivity, allergy, or contraindication to JS004,
toripalimab, or any of their formulation components.
13. Patients with any other malignancy, except for low-risk malignancies (5-year
survival rate >90%) such as fully treated basal cell or squamous cell skin cancer or
cervical carcinoma in situ.
14. Pregnant or breastfeeding women, or patients of reproductive potential unwilling or
unable to use effective contraception.
The investigator may also exclude patients if there are other factors that may lead to
premature discontinuation from the study, such as other serious concurrent illnesses
(including psychiatric disorders) requiring concomitant treatment, high risk of
recurrence of recent serious illness (e.g., myocardial infarction, stroke), severe
laboratory abnormalities, or family/social factors that may affect patient safety or data
collection.
Gender:
All
Minimum age:
18 Years
Maximum age:
75 Years
Healthy volunteers:
No
Start date:
September 30, 2024
Completion date:
September 30, 2026
Lead sponsor:
Agency:
Henan Provincial People's Hospital
Agency class:
Other
Source:
Henan Provincial People's Hospital
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06588335
