An Adjuvant Study to Evaluate SMS001 (Paclitaxel) in Non-Small Cell Lung Cancer

PRIMARY OBJECTIVES:

• To evaluate the safety and tolerability of SMS001 in Non-Small Cell Lung Cancer (NSCLC) patients undergoing cancer surgery.

SECONDARY OBJECTIVES:

• To evaluate tumor recurrence at 12-month follow-up in NSCLC lung cancer patients treated at a predefined dose.
• To evaluate disease free survival (DFS) for patients treated with SMS001 at the end of study.

Inclusion criteria

• Histopathological confirmed NSCLC
• Stage Ib, IIa, IIb or IIIa (N2) for both dose escalation and dose confirmation (NOTE: Staging will be according to the AJCC 8th edition)
• Age ≥18 years and suitable for lung cancer surgery
• No prior chemotherapy and/or thoracic radiation therapy
• Normal liver, and renal function at study entry
• Laboratory requirements:

• WBC > 2500/mm3
• Neutrophil >1500/mm3
• Hemoglobin >10 g/dL
• Platelet >100,000/ mm3
• AST and ALT < 2.5 x ULN
• Total bilirubin < 1.5 x ULN
• Creatinine < 2 mg/dL (equivalent to 176.8 μmol/L)
• Normal PT/INR and PTT
• eGFR >60mL/min/1.73m²
• QT interval corrected for heart rate using Frederica's formula (QTcF): males < 450msec and females < 470msec
• Operating surgeon deems patient is candidate for complete surgical resection of lung cancer and lymphadenectomy or lymph node sampling (Wedge resection, segmentectomy or lobectomy are acceptable)
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Ability to understand and sign informed consent
• Women of childbearing potential (WOCBP) must use highly effective methods of contraception for at least 6 months after wafer insertion. Otherwise, women must be postmenopausal (at least 1 y absence of vaginal bleeding or spotting and confirmed by follicle stimulating hormone [FSH] ≥40 mIU/mL [or ≥ 40 IU/L] if less than 2 y postmenopausal) or be surgically sterile. Men must use highly effective methods of contraception for at least 3 months after wafer insertion. Examples of highly effective contraception include: parenteral contraceptives, oral contraceptives, patch contraceptives, implantable hormonal contraceptives, intrauterine device or system, surgical sterilization (hysterectomy, bilateral oophorectomy, and/or bilateral salpingectomy), tubal ligation/occlusion, vasectomized partner, or sexual abstinence, if this is the subject's current practice. Periodic abstinence, i.e., calendar, symptothermal, or post-ovulation methods are not an acceptable form of contraception for this study.

Exclusion criteria

If a subject meets any of the following criteria, he/she must be excluded from the study.

• Evidence of locally advanced T3 or T4 NSCLC or distant metastatic disease.
• Patients requiring pneumonectomy or sleeve resection.
• Known sensitivity to any of the study agent components.
• Patients with a previous malignancy within the last 5 years except non-melanoma skin cancer.
• Patients receiving induction (neo-adjuvant) chemotherapy and/or radiation prior to surgery.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection. dysfunction of major organ (e.g., liver, kidney etc.), symptomatic congestive heart failure. unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant or nursing female subjects.
• Unwilling or unable to follow protocol requirements.
• Any other condition (e.g., psychiatric disorder) that, in the opinion of the Investigator, may interfere with the patient's ability to comply with the study requirements or visit schedule.