PACIFIC-9: D9078C00001

Lung cancer

Inclusion

• 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).
• Tumours harbouring mutations in any of the following genes, if known, as determined by existing local test results: ROS1, RET, MET, BRAF, NTRK1, NTRK2 and ERBB2 are excluded.
• 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.
• The platinum-based chemotherapy regimen must be cisplatin or carboplatin-based and contain one of the following agents: etoposide, vinblastine, vinorelbine, a taxane (paclitaxel or  docetaxel), or pemetrexed, according to the local standard of care regimens. Gemcitabine is not permitted.
• The last dose of chemotherapy must be administered prior to, or concurrently with, the final dose of radiation. Consolidation chemotherapy after radiation is not permitted. Up to 2 cycles of induction chemotherapy prior to cCRT is permitted.
• WHO performance (ECOG) status of 0 or 1 at randomization
• Adequate organ and marrow function

Key Exclusion Criteria:

• 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, basal cell carcinoma of the skin, squamous cell carcinoma of the skin or lentigo maligna that has undergone potentially curative therapy, adequately treated carcinoma in situ or Ta tumours treated with curative intent and without evidence of disease.
• Mixed small cell and non-small cell lung cancer histology.
• Participants who receive sequential (not inclusive of induction) chemoradiation therapy for locally advanced (Stage III) unresectable NSCLC.
• Participants with locally advanced (Stage III) unresectable NSCLC who have progressed during platinum-based cCRT.
• 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, organizing pneumonia, drug induced pneumonitis, or idiopathic pneumonitis, or evidence of active pneumonitis, ILD, pleural effusion, or 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

This is a Phase III, randomised, double-blind, multicentre, international study assessing the efficacy and safety of durvalumab (MEDI4736) in combination with oleclumab (MEDI9447) or durvalumab (MEDI4736) with monalizumab (IPH2201) in adults with locally advanced (Stage III), unresectable NSCLC, who have not progressed following platinum-based cCRT.

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