A Global Study to Assess the Effects of Durvalumab With Oleclumab or Durvalumab With Monalizumab Following Concurrent Chemoradiation in Patients With Stage III Unresectable Non-Small Cell Lung Cancer

Prior treatment

• History of another primary malignancy except for malignancy treated with curative intent with no known active disease ≥5 years before the first dose of study intervention and of low potential risk for recurrence, adequately resected non-melanoma skin cancer and curatively treated in situ disease, or adequately treated carcinoma in situ or Ta tumours without evidence of disease.
• Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
• Any unresolved toxicity CTCAE \>Grade 2 from the prior chemoradiation therapy (excluding alopecia).
• Participants with ≥grade 2 pneumonitis from prior chemoradiation therapy.
• History of idiopathic pulmonary fibrosis, drug-induced pneumonitis, or idiopathic pneumonitis - regardless of time of onset prior to randomisation. Evidence of active non-CRT induced pneumonitis (≥ Grade 2), active pneumonia, active ILD, active or recently treated pleural effusion, or current pulmonary fibrosis - diagnosed in the past 6 months prior to randomization.
• Active or prior documented autoimmune or inflammatory disorders (with exceptions)
• Current or prior use of immunosuppressive medication within 14 days before the first dose of durvalumab.

Other illness

• Mixed small cell and non-small cell lung cancer histology.

Other

• Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.

• Participant must be ≥ 18 years at the time of screening.
• Histologically- or cytologically-documented NSCLC and have been treated with concurrent CRT for locally advanced, unresectable (Stage III) disease
• Provision of a tumour tissue sample obtained prior to CRT
• Documented tumour PD-L1 status by central lab
• Documented EGFR and ALK wild-type status (local or central).
• Patients must not have progressed following definitive, platinum based, concurrent chemoradiotherapy
• Participants must have received at least 2 cycles of platinum-based chemotherapy concurrent with radiation therapy
• Participants must have received a total dose of radiation of 60 Gy ±10% (54 Gy to 66 Gy) as part of the chemoradiation therapy, to be randomised. Radiation therapy should be administered by intensity modulated RT (preferred) or 3D-conforming technique.
• WHO performance status of 0 or 1 at randomization
• Adequate organ and marrow function