Phase II, single-arm, open-label single center study that assess clinical feasibility and safety of 3 cycles neoadjuvant Toripalimab plus chemotherapy in rare mutations stage IIB-IIIB NSCLC followed by optional adjuvant treatment upon investigators' decisions.
30 eligible patients will be enrolled and 3 cycles of Toripalimab 240mg + chemotherapy (Nab-paclitaxel + carboplatin, or pemetrexed + carboplatin) will be administered. Rare mutations include RET fusions, BRAF (V600E or non-V600E but confirmed driver mutations), ERBB2 exon20 insertion, MET amplification (FISH confirmed) or exon 14 skipping. Dynamic blood samples before, during or after neoadjuvant treatment will be obtained for exploratory analysis. Patients who showed inferior response to neoadjuvant treatment leading to unresectable disease will be scheduled for local radiation or other potential subsequent treatment regarding multidisciplinary discussion. After completion of local treatment (surgery or radiation), patients will be provided with optional adjuvant treatment including chemotherapy or/and rare mutations TKI upon investigators' consideration. The primary objective of the study is pathological complete response (pCR) defined as no residue tumor found in both primary lung cancer and metastatic lymph nodes.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
30
240mg Q3W
135 mg/m2, d1, 8 Q3W
500mg/m2, d1 Q3W
AUC 5, d1 Q3W
Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences
Guanzhou, Guangdong, China
RECRUITINGPathological Complete Response (pCR)
Evaluation of the pathological complete response: The pathological complete response is defined as the absence of residual tumor in both lung and lymph nodes after neoadjuvant treatment.
Time frame: pCR will be assessed within 2 weeks after surgery
Major Pathological Response (MPR)
Percentage of Participants with Major Pathologic Response. MPR was defined as percentage of tumor cells within tumor bed less than 10% for both primary lung lesions and metastatic lymph nodes.
Time frame: MPR will be assessed within 2 weeks after surgery
Event-Free Survival (EFS)
Event-free survival (EFS) is defined as the length of time from initiation of neoadjuvant treatment to any of the following events: any progression of disease precluding surgery, progression or recurrence disease based on response evaluation criteria in solid tumors (RECIST) 1.1 after surgery, or death due to any cause.
Time frame: From date of initiation of neoadjuvant treatment to disease progression, reoccurrence, or death due to any cause, up to 36 months.
Overall Survival (OS)
Overall survival (OS) is defined as the time between the date of initiation of neoadjuvant treatment and the date of death.
Time frame: From date of initiation of neoadjuvant treatment to the date of all-cause death, assessed up to 60 months.
Adverse Events (AEs)
Incidence of all grade AE which has been confirmed to be correlated with neoadjuvant treatment or surgery.
Time frame: From date of initiation of neoadjuvant treatment till treatment discontinuation, assessed up to 14 weeks.
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