Neoadjuvant of Sintilimab Combined With Chemotherapy for Resectable NSCLC（neoSCORE）：A Prospective, Randomized, Open-Label, Single-Center Phase 2 Trial
Overview
- Phase
- Phase 2
- Sponsor
- Second Affiliated Hospital, School of Medicine, Zhejiang University
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Major pathological response rate (MPR)
Overview
Brief Summary
This is a Phase 2, prospective, randomized, open-Label, single-center international study that assesses the efficacy and safety of neoadjuvant therapy with different cycles of sintilimab combined with chemotherapy for resectable NSCLC. This trial will also explore the biomarkers of neoadjuvant immunochemotherapy.
Detailed Description
This is a Phase 2, prospective, randomized, open-Label, single-center international study that assesses the efficacy and safety of neoadjuvant therapy with different cycles of sintilimab combined with chemotherapy for resectable NSCLC. In this trial, eligible subjects will be randomly assigned to arm A and arm B (1:1). Subjects in arm A will receive 2 cycles of neoadjuvant chemotherapy with sintilimab + chemotherapy and arm B will receive 3 cycles of neoadjuvant chemotherapy with sintilimab + chemotherapy, followed by surgery within the 4th week after the last dose of sintilimab. After operation, subjects in arm A will receive 2 cycles of adjuvant chemotherapy and arm B will receive 1 cycle of adjuvant chemotherapy, followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients. The primary purpose is MPR rate of neoadjuvant chemotherapy of resectable NSCLC with different cycles of sintilimab combined with platinum-based chemotherapy, which is defined as the percentage of participants having ≤10% viable tumor cells in the pathological examination of resected specimens.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- None
Eligibility Criteria
- Ages
- 18 Years to 75 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Sign the informed consent form before starting any trial related procedure.
- •18-75 years old, male or female.
- •Non-small cell lung cancer confirmed by cytology or histology.
- •There must be at least one evaluable focus judged according to recist1.1 standard.
- •Evaluation by the researchers to confirm resectable stage cⅠb-Ⅲa NSCLC patients without any treatment before.
- •ECOG PS 0-
- •Life expectancy \> 6 months.
- •Adequate organ function and it should meet the following criteria:
- •No use of Granulocyte colony stimulating factor within 14 days, absolute neutrophils count(ANC)≥1.5x109/L, platelets count(PLT)\>9g/dL, hemoglobin(HB)≥100×109/L;
- •Total bilirubin(TBIL)≤1.5ULN, ALT、AST≤ 2.5 ULN, serum creatinine(sCr)≤1.5ULN;
Exclusion Criteria
- •Malignancies within 5 years prior to the first dose(excluding radical skin basal cell carcinoma, skin squamous cell carcinoma and / or radical resection of carcinoma in situ).
- •Currently participating in the intervention clinical treatment, or receiving other drugs or research instruments within 4 weeks before the first dose.
- •Patients who have had prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, or drugs for another stimulation or synergistic inhibition of T cell receptor (e.g. CTLA-4, OX-40, CD137).
- •Active autoimmune diseases requiring systemic treatment (e.g. using disease improving drugs, corticosteroids or immunosuppressants) occurred within 2 years before the first dose. Alternative therapies (e.g. thyroxine, insulin or corticosteroids in physiological doses for adrenal or pituitary insufficiency) are not considered systemic treatment.
- •Systemic glucocorticoid therapy (excluding local glucocorticoids by nasal spray, inhalation or other routes) or any other form of immunosuppressive therapy is in progress within 7 days before the first dose.
- •Note: it is allowed to use physiological dose of glucocorticoid (Prednisone≤10 mg/d or equivalent drug).
- •Received allogeneic organ transplantation (except corneal transplantation) or allogeneic hematopoietic stem cell transplantation.
- •Allergic to study drug(sintilimab, pemetrexed, carboplatin, albumin-bound paclitaxel) components excipients.
- •Not fully recovered from toxicity and/or complications caused by any intervention before treatment (≤level 1 or reach baseline, excluding fatigue or hair loss).
- •Has a known history of human immunodeficiency virus (HIV) infection (HIV 1/2 antibody positive).
Arms & Interventions
sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)
Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the second dose of sintilimab; Followed by 2 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.
Intervention: sintilimab (Biological)
sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)
Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the second dose of sintilimab; Followed by 2 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.
Intervention: pemetrexed (Drug)
sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)
Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the second dose of sintilimab; Followed by 2 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.
Intervention: Carboplatin (Drug)
sintilimab+chemotherapy(2 cycles of neoadjuvant chemotherapy)
Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the second dose of sintilimab; Followed by 2 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.
Intervention: albumin-bound paclitaxel (Drug)
sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)
Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the third dose of sintilimab; Followed by 1 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.
Intervention: sintilimab (Biological)
sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)
Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the third dose of sintilimab; Followed by 1 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.
Intervention: pemetrexed (Drug)
sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)
Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the third dose of sintilimab; Followed by 1 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.
Intervention: Carboplatin (Drug)
sintilimab+chemotherapy(3 cycles of neoadjuvant chemotherapy)
Patients with nonsquamous NSCLC (including adenocarcinoma, large cell carcinoma and unspecified type) : sintilimab + pemetrexed + carboplatin; Patients with squamous NSCLC : sintilimab + albumin-bound paclitaxel + carboplatin; Followed by surgery within the 4th week after the third dose of sintilimab; Followed by 1 cycles of adjuvant chemotherapy, the researcher will decide whether to radiotherapy or not according to the clinical situation and pathological stage of the patient; Followed by the maintenance treatment of sintilimab for up to 1 year according to the requirements of patients.
Intervention: albumin-bound paclitaxel (Drug)
Outcomes
Primary Outcomes
Major pathological response rate (MPR)
Time Frame: At time of surgery
MPR rate is defined as the percentage of participants having ≤10% viable tumor cells in the pathological examination of resected specimens.
Secondary Outcomes
- Objective response rate (ORR)(prior to surgery)
- 2 years disease-free survival rate (DFS)(2 years postoperatively)
- Pathology complete response rate(pCR)(At time of surgery)
- 2 years overall survival rate (OS)(2 years postoperatively)