A Phase II, Open-label, Multicentre, Randomised Study of Neoadjuvant and Adjuvant Treatment in Patients With Resectable, Early-stage (II to IIIB) Non-small Cell Lung Cancer (NeoCOAST-2)

This is a open-label, multi-arms, multicentre, randomised study, eligible participants will be enrolled and randomised to one of the following treatment regimens.

Arm 1: Participants will receive Oleclumab + durvalumab + platinum doublet chemotherapy as neoadjuvant treatment and Oleclumab + durvalumab as adjuvant treatment.

Arm 2: Participants will receive Monalizumab + durvalumab + platinum doublet chemotherapy as neoadjuvant treatment and Monalizumab + durvalumab as adjuvant treatment.

Arm 3: Participants will receive MEDI5752 + platinum doublet chemotherapy as neoadjuvant treatment and MEDI5752 as adjuvant treatment.

Arm 4: Participants will receive Dato-DXd + durvalumab + single agent platinum chemotherapy as neoadjuvant treatment and durvalumab as adjuvant treatment.

Arm 5: Participants will receive AZD0171 + durvalumab + platinum doublet chemotherapy as neoadjuvant treatment and AZD0171 + durvalumab as adjuvant treatment.

Inclusion Criteria:

• Newly diagnosed NSCLC patients with resectable disease (Stage IIA to Stage IIIB).
• WHO or Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• Adequate organ and bone marrow function.
• Provision of tumour samples (newly acquired or archival tumour tissue [≤ 6 months old]) to confirm Programmed death-ligand 1 (PD-L1) status, epidermal growth factor receptor (EGFR), or anaplastic lymphoma kinase (ALK) status.
• Adequate pulmonary function.

Exclusion Criteria:

• Participants with sensitising EGFR mutations or ALK translocations.
• History of allogeneic organ transplantation.
• Active or prior documented autoimmune or inflammatory disorders.
• Uncontrolled intercurrent illness, uncontrolled hypertension, unstable angina pectoris, uncontrolled cardiac arrhythmia, active bleeding diseases, serious chronic gastrointestinal conditions associated with diarrhoea, or psychiatric illness/social situations that would limit compliance with study requirement.
• History of another primary malignancy.
• Participants with small-cell lung cancer or mixed small-cell lung cancer.
• History of active primary immunodeficiency.
• History of non-infectious ILD/pneumonitis that required steroids, has current ILD/pneumonitis, or has suspected ILD/pneumonitis that cannot be ruled out by imaging at screening.
• Participants who have preoperative radiotherapy treatment as part of their care plan.
• Participants who require or may require pneumonectomy, segmentectomies, or wedge resections, as assessed by their surgeon at baseline, to obtain potentially curative resection of primary tumour.
• QTcF (QT interval corrected by Fridericia's formula) interval ≥ 470 ms.
• Any medical contraindication to treatment with chemotherapy as listed in the local labelling.
• Participants with moderate or severe cardiovascular disease.
• Any concurrent chemotherapy, investigational product, biologic, or hormonal therapy for cancer treatment.
• Receipt of live attenuated vaccine within 30 days prior to the first dose of study interventions.
• Prior exposure to approved or investigational immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies. Participants who received agents targeting the adenosine pathway, anti-NKG2A, anti-HLA-E agents, and anti-LIF agents are also excluded. Participants who have received previous treatment with a TROP2 targeting ADC or with another ADC containing a chemotherapy agent that inhibits TOP1 activity are also excluded.
• Current or prior use of immunosuppressive medication within 14 days before the first dose of study interventions.
• Active or uncontrolled infections including HBA, HBV, HCV, and HIV.