neoadjuvant and adjuvant treatment in resectable non-small cell lung cancer

Conditions: Non-small Cell Lung Cancer

Summary: the study is intended to assess the safety and efficacy of perioperative treatment with durvalumab in combination with oleclumab, monalizumab, or azd0171 and platinum doublet chemotherapy (ctx); or volrustomig or rilvegostomig in combination with ctx; or datopotamab deruxtecan (dato-dxd) in combination with durvalumab or rilvegostomig and single agent platinum chemotherapy in participants with resectable, early-stage non-small cell lung cancer.

this is an 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 + ctx as neoadjuvant treatment and oleclumab + durvalumab as adjuvant treatment. arm 2: participants will receive monalizumab + durvalumab + ctx as neoadjuvant treatment and monalizumab + durvalumab as adjuvant treatment. arm 3: participants will receive volrustomig (dose exploration) + ctx as neoadjuvant treatment and volrustomig 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 + ctx as neoadjuvant treatment and azd0171 + durvalumab as adjuvant treatment. arm 6: participants will receive rilvegostomig + ctx as neoadjuvant treatment and rilvegostomig as adjuvant treatment. arm 7: participants will receive dato-dxd + rilvegostomig + single agent platinum chemotherapy as neoadjuvant treatment and rilvegostomig as adjuvant treatment.

Eligibility criteria:
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. * participants with baseline pd-l1 expression status \<1% (arms 6 and 7 only). * 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 interstitial lung disease (ild) 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-tigit (t cell immunoreceptor with ig and itim domains), 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.

Keywords: lung cancer early-stage durvalumab oleclumab monalizumab azd0171 datopotamab deruxtecan neoadjuvant adjuvant chemotherapy volrustomig rilvegostomig