Lung Cancer
Conditions
Brief summary
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.
Interventions
DRUGSacituzumab Govitecan
* 4 cycles, each cycle lasting for 3 weeks * 10mg/kg given every day 1 and day 8 each cycle * IV infusion
DRUGPembrolizumab
* 4 cycles, each cycle lasting for 3 weeks in Neoadjuvant phase; after surgery, 13 cycles, each cycle lasting for 3 weeks in Maintenance phase. * 200mg fixed dose every day 1 each cycle * IV infusion
Sponsors
Chinese University of Hong Kong
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Female or male patients, 18 years of age or older, able to understand and give written informed consent 2. Pathologically proven NSCLC 3. Tumour tested negative for EGFR and ALK 4. Measurable disease by CT as per RECIST Version 1.1 criteria by investigator 5. Tumour tissue is available for translational research (preferably histology, cytology allowed) 6. 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 7. Eastern Cooperative Oncology Group (ECOG) Performance Status 0-1 8. 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 9. Adequate hepatic function: bilirubin ≤ 1.5 x ULN, AST/ALT ≤ 2.5 x ULN 10. Adequate renal function: calculated creatinine clearance ≥ 30 ml/min, according to the formula of Cockcroft-Gault equation 11. 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. 12. 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. 13. 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. 14. Willing and able to comply with the requirements and restrictions in this protocol.
Exclusion criteria
1. Presence of any distant metastasis 2. Previous or concomitant malignancy within 5 years prior registration with the exception of adequately treated localized non-melanoma skin cancer or cervical carcinoma in situ. Prior anti-cancer treatment can be accepted except for drugs listed in
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Pathological complete response (pCR) rate in the intention-to-treat population | 2 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Resection rate after neoadjuvant SG and pembrolizumab combination: proportion of patients who undergo surgery with curative intent | 2 years | — |
| pCR rates in patients who undergo surgery | 2 years | — |
| Major pathological response (MPR) rate in the ITT population and in patients who undergo surgery: MPR is defined as less than 10% viable tumor cells in resected primary tumour specimen | 2 years | — |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 while on neoadjuvant SG and pembrolizumab combination | 2 years | — |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 while on adjuvant pembrolizumab | 2 years | — |
| Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 first 30 days after surgery | 2 years | — |
| Objective response rate (ORR): rate of partial and complete response on CT scans according to RECIST criteria ver 1.1 | 2 years | — |
| Overall Survival | 2 years | — |
| 12 month and 24 month event-free survival (EFS) rate | 2 years | — |
| Patient reported quality of life (QOL), as measured by EQ-5D-3L during study treatment. | 2 years | For the descriptive system of EQ-5D-3L, three levels of problems are described in each dimension. For the Visual Analogue Scale (VAS), the overall health assessment of the respondent is captured, ranging from 0 (worst health imaginable) to 100 (best health imaginable) |
Countries
Hong Kong
Outcome results
None listed