Neoadjuvant Immunotherapy for Stage III Non-small Cell Lung Cancer

Official title

Neoadjuvant Sintilimab or Combined With Chemotherapy for Stage III Driven Gene Mutation Negative Non-small Cell Lung Cancer

Overview

This is a phase II, non-randomized, open-label, multi-center study to evaluate the efficacy of neoadjuvant Sintilimab (PD-1 antibody) or combined with chemotherapy as first-line treatment in patients with stage III non-small cell lung cancer (NSCLC).

Interventions

• Drug Sintilimab
  Neoadjuvant treatment stage: Sintilimab 200mg, q3w, i.v., 2-4 cycles, then receive chest CT evaluation. Surgery stage: the patients will receive radical surgery after the neoadjuvant treatment. Adjuvant treatment stage: according to the NCCN guidelines.
• Drug Chemotherapy
  Neoadjuvant treatment stage: Sintilimab 200mg, q3w, i.v., 2-4 cycles; platinum-based chemotherapy (Non-squamus: Carboplatin AUC 5 + Pemetrexed 500mg/m2; Squamous: Carboplatin AUC 5 + Gemcitabine 1000mg/m2 or Paclitaxel 200mg/m2) q3w, i.v., 2-4 cycles, then receive chest CT evaluation. Surgery stage: the patients will receive radical surgery after the neoadjuvant treatment. Adjuvant treatment stage: according to the NCCN guidelines.

Primary outcome measures

• Major pathologic response (MPR) [Time frame: up to 5 months]

Secondary outcome measures (5)

• Objective response rate (ORR) [Time frame: up to 4 months]
• Disease-free survival (DFS) [Time frame: up to 60 months]
• Progression-free survival (PFS) [Time frame: up to 60 months]
• Overall survival (OS) [Time frame: up to 60 months]
• Safety: frequency of severe adverse events [Time frame: up to 6 months]

Eligibility criteria

Inclusion criteria

• The patient shall sign the Informed Consent Form.
• Aged 18 ≥ years.
• Histological or cytological diagnosis of NSCLC by needle biopsy, and stage III confirmed by imageological examinations (CT, PET-CT or EBUS).
• Eastern Cooperative Oncology Group (ECOG) performance-status score of 0 or 1.
• Life expectancy is at least 12 weeks.
• At least 1 measurable lesion according to RECIST 1.1.
• With the feasiblility or anticipated feasiblility after neoadjuvant therapy to receive radical surgery;
• Patients with good function of other main organs (liver, kidney, blood system, etc.):

• ANC count ≥1.5×10\^9/L, platelet count ≥100×10\^9/L，hemoglobin ≥90 g/L;
• the international standard ratio of prothrombin time (INR) and prothrombin time (PT) < 1.5 times of upper limit of normal (ULN);
• Partial thromboplastin time (APTT) ≤1.5×ULN;
• Total bilirubin ≤1.5×ULN;
• Alanine aminotransferase (ALT) aspartate aminotransferase (AST) ≤2.5×ULN, or ALT and AST ≤5×ULN in the patients with liver metastatic tumor.
• Patients with normal lung function can tolerate surgery;
• Without systematic metastasis (including M1a, M1b and M1c);
• Fertile female patients must voluntarily use effective contraceptives not less than 120 days after chemotherapy or the last dose of Sintilimab (whichever is later) during the study period, and urine or serum pregnancy test results within 7 days prior to enrollment are negative.
• Unsterilized male patients must voluntarily use effective contraception during the study period not less than 120 days after chemotherapy or the last dose of Sintilimab (whichever is later).

Exclusion criteria

• Non-squamous cell carcinoma with EGFR active mutation positive or ALK rearrangement;
• Participants who have received any systemic anti-cancer treatment for thymic epithelial tumor, including surgical treatment, local radiotherapy, cytotoxic drug treatment, targeted drug treatment and experimental treatment;
• Administration of any Chinese medicine against cancer before administration of the drug;
• Participants with other cancer (excluding cervical carcinoma in situ, cured basal cell carcinoma, bladder epithelial tumor \[including TA and tis\]) within five years before the start of this study;
• Participants with any unstable systemic disease (including active infection, uncontrolled hypertension), unstable angina pectoris, angina pectoris starting in the last three months, congestive heart failure (>= NYHA) Grade II), myocardial infarction (6 months before admission), severe arrhythmia requiring drug treatment, liver, kidney or metabolic diseases;
• With activate or suspectable autoimmune disease, or autoimmune paracancer syndrome requiring systemic treatment;
• Antibiotics were used to treat the infection for 4 weeks prior to the start of the trial;
• Participants who were systemically treated with corticosteroids (prednisone or other corticosteroids >10 mg/ day) or other immunosuppressive agents within 2 weeks prior to first administration. In the absence of active autoimmune disease, inhaled or topical corticosteroids and adrenal hormone replacement therapy with a dose of less than 10 mg/ day of prednisone are permitted;
• Participants who are allergic to the test drug or any auxiliary materials;
• Participants with active hepatitis B, hepatitis C or HIV;
• The vaccine was administered within 4 weeks of the start of the trial;
• Participants who have undergone major surgery or severe trauma in other systems within 2 months before the start of this trial;
• Pleural effusion, pericardial effusion or ascites that are not clinically controlled and require pleural puncture or abdominal puncture drainage within 2 weeks before inclusion;
• The patients have active pia meningioma, uncontrolled or untreated brain metastases;
• Pregnant or lactating women;
• Participants suffering from nervous system diseases or mental diseases that cannot cooperate;
• Participated in another therapeutic clinical study;
• Other factors that researchers think it is not suitable for enrollment.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Non-randomized

Model

Single group

Masking

Open label

Primary purpose

Treatment

Study locations

China · 1 center

• Shanghai Pulmonary Hospital — Shanghai

Identifiers

NCT: NCT04728724 · LungMate-009

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗