Study to Assess Neoadjuvant Durvalumab (D) and Platinum-Based Chemotherapy (CT), Followed by Either Surgery and Adjuvant D or CRT and Consolidation D, in Resectable or Borderline Resectable Stage IIB-IIIB NSCLC (MDT-BRIDGE)

This will be a multicentre, Phase II, single-arm, global study assessing the efficacy and safety of neoadjuvant durvalumab and platinum-based CT, given intravenously, followed by either surgery and adjuvant durvalumab or definitive CRT and consolidation durvalumab in participants with resectable and borderline resectable stage IIB-IIIB NSCLC.

Neoadjuvant Period A:

All participants will initially receive 2 cycles of neoadjuvant durvalumab + CT (investigator's choice platinum-based) every three weeks. Participants will be assessed for resectability by a multidisciplinary team.

Neoadjuvant Period B:

Cohort 1: Participants who are deemed eligible for surgery will receive study intervention every three weeks for an additional one and up to two cycles, followed by surgery.

CRT:

Cohort 2: Participants with unresectable tumours (according to MDT re-assessment) will receive definitive CRT (6 one-week cycles) for approximately six weeks.

Both cohorts will then go on to receive durvalumab every four weeks until disease progression or recurrence or up to one year.

Inclusion criteria

• Deemed resectable or borderline resectable at baseline, confirmed by MDT evaluation at diagnosis.
• Previously untreated and pathologically confirmed Stage IIB to select [i.e.N2] Stage IIIB by AJCC v8.
• Nodal status confirmed with whole body FDG-PET and biopsy via endobronchial ultrasound, mediastinoscopy, or thoracoscopy.
• Mandatory brain MRI.
• EGFR and ALK wild-type.
• Medically operable: adequate cardiac and lung function to undergo resection.
• Participant must be ≥ 18 years, at the time of screening.
• Histologically or cytologically documented NSCLC.
• Minimum life expectancy of 12 weeks.
• Minimum body weight of 30 kg.
• Male and female participants must be willing to use acceptable methods of contraception.
• Female participants of childbearing potential must have negative pregnancy test.

Exclusion criteria

• Unresectable NSCLC confirmed by MDT evaluation at baseline
• Stage IIIC patients
• Participants whose planned surgery at enrollment is a wedge resection
• Known EGFR mutation or ALK translocation
• Participants contraindicated for surgical intervention due to comorbid conditions
• Participants who are allergic to study intervention.
• Participants with more than one primary tumour.
• Known active hepatitis infection, positive HCV antibody, HBsAg or HBV core antibody (anti-HBc), at screening.
• Female participants who are pregnant or breastfeeding.
• Judgement by the investigator that the participant should not participate in the study.
• Previously infected or tested positive for human immunodeficiency virus.