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A Study to Evaluate the Benefit of Adding Durvalumab After Chemotherapy, Durvalumab and Surgery in Patients With Early-stage, Operable, Non-small Cell Lung Cancer.

ACTRN 12624001373561

Brief Summary

The aim of this study is to determine whether additional adjuvant immunotherapy with durvalumab after neoadjuvant chemo-immunotherapy has an effect on disease-free survival (DFS) in patients who do not achieve complete pathological response (pCR) as per local assessment according to the IASLC recommendations.

Intervention/Treatment

  • Drug: Adjuvant durvalumab

Inclusion Criteria

  1. Histologically confirmed NSCLC.
  2. Stage IIB-IIIB (T1-4 N0-2) according to 8th edition of the TNM staging system of lung cancer.
    • Stage III assessment should include samples of lymph nodes at levels 4, bilaterally, and level 7 to rule out stage IIIB N3 disease.
    • T4 tumours will only be eligible if they are defined as T4 based only on their size (>7cm); any other reason will be considered ineligible.
  3. Known PD-L1 status, as tested locally using a validated assay. To ensure comparability of results, it is strongly encouraged that PD-L1 testing is done with the Ventana PD-L1 (SP263) assay.
  4. Absence of EGFR mutation or ALK translocation, as tested locally.
  5. Primary tumour resectable and functionally operable as assessed per local multidisciplinary tumour board (cardiac evaluation, pulmonary function and diffusion capacity, comorbidity).
  6. Adequate haematological function:
    • Haemoglobin greater than/equal to 90 g/L
    • Absolute neutrophil count (ANC) greater than/equal to 1.5 x10^9/L
    • Platelet count greater than/equal to 100 x10^9/L.
  7. Adequate renal function: Measured creatinine clearance (CL) >40 mL/min or calculated
    CL >40 mL/min calculated by the Cockcroft-Gault formula (greater than/equal to 45mL/min for pemetrexed-based chemotherapy, greater than/equal to 60mL/min for cis-platinum-based chemotherapy).
  8. Adequate liver function:
    • ALT and AST less than/equal to 2.5x institutional ULN
    • Total serum bilirubin less than/equal to 1.5x institutional ULN (patients with Gilbert’s syndrome may be allowed to be enrolled after consultation with the study team.
  9. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
  10. Patient has to be fit to receive at least one of the platinum-based chemotherapy regimens as indicated in the protocol, according to local standards.
  11. Age greater than/equal to 18 at the time of enrolment.
  12. Body weight >30 kg.
  13. Life expectancy of at least 12 weeks.
  14. Women of childbearing potential, including women who had their last menstruation in the last 2 years, must have a negative urinary or serum pregnancy test at screening before enrolment. Pregnancy test must be repeated within 3 days before the first dose of protocol treatment.
  15. Written IC for study participation must be signed and dated by the patient and the investigator prior to any study-related intervention.

Eligibility Criteria for randomisation:

  1. Surgical resection must have been completed. Note: Participants who have had only had segmentectomy or wedge resections are not eligible for randomisation.
  2. Patients must have complete resection: R0 or R1 resection.
  3. Patients must be fit to receive adjuvant treatment with durvalumab.
  4. Patients must have no evidence of metastatic disease as assessed by CT scan.
  5. Documentation of pathological response as per local review must be available.

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