Clinical trial NCT03623776: Neoadjuvant JS001, or JS001 in Combination With Pemetrexed and Carboplatin in Resectable NSCLC.
Official title: A Multicenter Phase II Trial of Neoadjuvant JS001, or JS001 in Combination With Chemotherapy in Resectable NSCLC.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE2
Conditions: Efficacy and Safety
Keywords: Non-Small Cell Lung Cancer
Neoadjuvant
Programmed Death-1
Lead sponsor: Sun Yat-sen University
Sponsor class: OTHER
First posted: 2018-08-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: JS001 (Toripalimab) is a recombinant humanized anti-PD-1 monoclonal antibody, which selectively interferes with the combination of PD-1 with its ligands, PD-L1 and PD-L2. The purpose of this study is to studying neoadjuvant JS001, or JS001 in combination with pemetrexed and carboplatin to see how well it works in treating patients with resectable NSCLC.

Detailed description: Surgery in combination with preoperative or postoperative chemotherapy is the recommended therapeutic approach for patients with resectable non-small cell lung cancer (NSCLC). However, the prognosis of early-stage NSCLC remains to be improved, with 5-year survival rates ranging from 50% for stage IA to 20% for stage IIIA. Antibodies that block the PD-1 protein have provided a major treatment advance in patients with cancer. JS001 (Toripalimab) is a recombinant humanized anti-PD-1 monoclonal antibody, which has shown its efficacy in the treatment of a variety of malignancies. This study is to studying neoadjuvant JS001, or JS001 in combination with chemotherapy to see how well it works in treating patients with resectable NSCLC.

Eligibility criteria: Inclusion Criteria:

* Target population is high risk NSCLC with resection option for potential cure, as assessed by a faculty surgeon at SYSUCC. This may include clinical stage IB (≥4cm), II and IIIA. Subjects with N3 nodal involvement are not included.
* Subjects should not have a previously detected sensitizing EGFR mutation or ALK fusion oncogene.
* Written informed consent provided.
* Male and female patients aged ≥18 years, \< 75 years.
* Able to comply with the required protocol and follow-up procedures, and able to receive oral medications.
* Blood and specimens before and after treatment must be provided
* Eastern Cooperative Oncology Group (ECOG) performance status of 0-1.
* Life expectancy ≥12 weeks.
* Adequate hematological function: Absolute neutrophil count (ANC) ≥2.0 x 109/L, and Platelet count ≥100 x 109/L, and Hemoglobin ≥9 g/dL (may be transfused to maintain or exceed this level).
* Adequate liver function: Total bilirubin ≤ 1.5 x upper limit of normal (ULN), Aspartate aminotransferase (AST), alanine aminotransferase (ALT) ≤ 2.5 x ULN in subjects without liver metastases; ≤ 5 x ULN in subjects with liver metastases.
* Adequate renal function: Serum creatinine ≤ 1.25 x ULN, or ≥ 60 ml/min.
* Female subjects should not be pregnant or breast-feeding.

Exclusion Criteria:

* Known severe hypersensitivity to JS001 or any of the excipients of this product.
* Prior therapy with anti-PD-1, anti-PD-L1, anti-PD-L2, or anti-CTLA-4 antibody (including any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways).
* Prior chemotherapy or radiotherapy.
* Subjects with active, known or suspected autoimmune disease. Subjects in conditions not expected to recur in the absence of an external trigger, or not requiring systemic treatment are permitted to enroll.
* Subjects with a condition requiring systemic treatment with either corticosteroids (\>10 mg daily prednisone equivalent) or other immunosuppressive medications within 14 days of first administration of study treatment. Inhaled or topical steroids, and adrenal replacement steroid doses \> 10 mg daily prednisone equivalent, are permitted in the absence of active autoimmune disease.
* Inability to comply with protocol or study procedures.
* A serious concomitant systemic disorder that, in the opinion of the investigator, would compromise the patient's ability to complete the study.
* A serious cardiac condition, such as myocardial infarction within 6 months, angina, or heart disease.
* History of another malignancy in the last 5 years with the exception of the following: other malignancies cured by surgery alone and having a continuous disease-free interval of 5 years are permitted. Cured basal cell carcinoma of the skin and cured in situ carcinoma of the uterine cervix are permitted.
* Any unstable systemic disease (including active infection, uncontrolled hypertension, unstable angina, congestive heart failure, myocardial infarction within the previous year, serious cardiac arrhythmia requiring medication, hepatic, renal, or metabolic disease).
* Patient who has active serious infection (e.g. pyrexia of or 38.0℃ over)
* Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS).
* Known history of active Hepatitis B or C.
* Women who are pregnant or nursing.
* Evidence of any other disease, neurological or metabolic dysfunction, physical examination or laboratory finding giving reasonable suspicion of a disease or condition that contraindicated the use of an investigational drug or puts the subject at high risk for treatment-related complications.

Primary outcomes:
measure: 3-year Disease Free Survival
timeFrame: 3 years after the last patient is registered
Secondary outcomes:
measure: Number of participants with treatment-related adverse events (AEs)
timeFrame: 2 years after the last patient is registered
measure: Number of participants with perioperative complications
timeFrame: 2 years
measure: 3-year Overall survival
timeFrame: 3 years after the last patient is registered
measure: Pathologic Response
timeFrame: 3 months
Other outcomes:
Locations:
city: Guangzhou
country: China
facility: Sun Yat-sen University Cancer Center
state: Guangdong
Study officials:
affiliation: Sun Yat-sen University
name: Si-Yu Wang
role: PRINCIPAL_INVESTIGATOR
References: