Neoadjuvant Sacituzumab Govitecan Plus Pembrolizumab in Resectable Non-Small Cell Lung Cancer: an Open-label, Multicenter, Single Arm Phase 2 Study
The combination of neoadjuvant immunotherapy plus chemotherapy has recently been shown to improve survival outcome compared to chemotherapy alone and was recently approved for resectable non-small cell lung cancer (NSCLC). Despite so, recurrence risk of NSCLC after surgical resection remains high. Sacituzumab govitecan, a novel antibody drug conjugate, was demonstrated to be clinically active in metastatic NSCLC. This study aims to study the clinical efficacy of sacituzumab govitecan plus immunotherapy in resectable NSCLC. This is a open-label, single arm, multicentre, phase II study. Patients with EGFR/ALK negative, stage II-III (AJCC 8th edition), resectable NSCLC are eligible and will receive 4 cycles of neoadjuvant pembrolizumab plus sacituzumab govitecan, followed by surgical resection of tumour, and then 13 cycles of maintenance pembrolizumab.
• Female or male patients, 18 years of age or older, able to understand and give written informed consent
• Pathologically proven NSCLC
• Tumour tested negative for EGFR and ALK
• Measurable disease by CT as per RECIST Version 1.1 criteria by investigator
• Tumour tissue is available for translational research (preferably histology, cytology allowed)
• AJCC 8th edition Stage II-III based on the following diagnostic workup and tumour is considered potentially resectable
‣ Distant metastasis staging by PET/CT whole body or CT thorax and upper abdomen with contrast
⁃ Patients with stage IIIB (N2) that is considered potentially resectable by cardiothoracic surgeon may be enrolled
• Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1
• Adequate haematological values without transfusional or growth factor support within 2 weeks of study drug initiation: haemoglobin ≥ 9.0g/dL, absolute neutrophil count ≥ 1.5 x 10\^9/L, platelet count ≥ 100 x 10\^9/L
• Adequate hepatic function: bilirubin ≤ 1.5 x ULN, AST/ALT ≤ 2.5 x ULN
⁃ Adequate renal function: calculated creatinine clearance ≥ 30 ml/min, according to the formula of Cockcroft-Gault equation
⁃ Male patients and female patients of childbearing potential who engage in heterosexual intercourse must agree to use protocol-specified method(s) of contraception as described in Appendix V.
⁃ Patients with HBV (HBsAg +ve) must be on antiviral therapy and have a well-controlled HBV infection as determined by investigator. Patients who test positive for hepatitis B core antibody (anti-HBc) will require HBV DNA by quantitative polymerase chain reaction (PCR) for confirmation of active disease. Participants should remain on anti-viral therapy throughout study intervention and follow local guidelines for HBV anti-viral therapy post completion of study intervention.
⁃ Patients with known HCV infection (positive hepatitis C antibody) (testing is not mandatory for trial enrolment) must have been treated with antiviral therapy and have undetectable HCV viral load.
⁃ Willing and able to comply with the requirements and restrictions in this protocol.