ADOPT-lung is an international, multicentre, randomized, stratified, open-label, two-arm, phase III trial, using pathological response, histology, stage and PD-L1 as stratification factors, to evaluate the activity of additional adjuvant immunotherapy (durvalumab) after neoadjuvant chemo-immunotherapy in terms of disease free survival (DFS), in patients with treatment-naïve resectable stage IIB-IIIB (N2) NSCLC who do not achieve a complete pathological response, as well as in the overall randomized population

Cohorts:
290 randomised patients with non-pCR
ITT cohort of 364 patients (with and without pCR)

The trial consists of two treatment arms:

• Adjuvant durvalumab in the experimental arm
• Observation in the control arm

Neoadjuvant treatment phase (before randomization):
Neoadjuvant durvalumab consists of 3-4 cycles of durvalumab given at a fixed dose of 1500 mg i.v. every 3 weeks (±1 week).

If durvalumab is given in combination with chemotherapy, durvalumab should be administered prior to chemotherapy but on the same day as chemotherapy.

• All histologies:
  • Carboplatin (AUC 5 or 6) plus paclitaxel (175 or 200 mg/m2 i.v.).
• Squamous NSCLC:
  • Cisplatin (75 mg/m2 i.v.) plus gemcitabine (1000 or 1250 mg/m2 i.v.) or
  • Carboplatin (AUC 5 or 6) plus gemcitabine (1000 or 1250 mg/m2 i.v.).
• Non-squamous NSCLC:
  • Cisplatin (75 mg/m2 i.v.) plus pemetrexed (500 mg/m2 i.v.) or
  • Carboplatin (AUC 5 or 6) plus pemetrexed (500 mg/m2 i.v.).

Patients who have completed the neoadjuvant treatment and who meet the eligibility criteria for randomization can be randomized.
Patients are randomly assigned (1:1) to one of the two treatment arms: adjuvant durvalumab (experimental arm) or observation (control arm). Adjuvant treatment for patients randomized in the experimental arm should then start within 12 weeks after surgery.

Adjuvant treatment phase after randomization
Durvalumab is given at a fixed dose of 1500 mg i.v. every 4 weeks (±1 week) until relapse or unacceptable toxicity, for a maximum of 12 cycles after surgery.

The primary endpoint of this study is disease free survival in patients without pCR, measured from randomization.

Key secondary outcome is disease free survival in the Intention to treat (ITT) cohort (with and without pCR), measured from randomization

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.
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, liver- and renal function
7. Eastern Cooperative Oncology Group (ECOG) performance status 0-1.
8. Life expectancy of at least 12 weeks

1. T4 with invasion of heart, great vessels, carina, trachea, oesophagus, or spine
2. Any previous or concurrent treatments for NSCLC
3. Any previous immunotherapy
4. Major surgical procedure (as per investigators assessment) within 28 days before enrolment.
5. History of allogenic organ transplantation
6. Active or prior documented autoimmune disease or inflammatory disorders
7. Uncontrolled intercurrent illness
8. Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab. The following are exceptions to this criterion.
9. History of another primary malignancy except for
   • Malignancy treated with curative-intent and with no known active disease 5 years before the first dose of durvalumab and of low potential risk for recurrence
   • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease
   • Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease