Non-small Cell Lung Cancer
Conditions
Keywords
Lung Cancer, early-stage, Durvalumab, Oleclumab, Monalizumab, AZD0171, Datopotamab Deruxtecan, Neoadjuvant, Adjuvant, Chemotherapy, Volrustomig, Rilvegostomig
Brief 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.
Detailed description
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.
Interventions
DRUGDurvalumab
Participants will receive Durvalumab via intravenous route.
DRUGOleclumab
Participants will receive Oleclumab via intravenous route.
DRUGMonalizumab
Participants will receive Monalizumab via intravenous route.
DRUGDato-DXd
Participants will receive datopotamab deruxtecan (Dato-DXd) via intravenous route.
DRUGAZD0171
Participants will receive AZD0171 via intravenous route.
DRUGCarboplatin
Carboplatin as chemotherapy
DRUGCisplatin
Cisplatin as chemotherapy
Pemetrexed/Cisplatin as chemotherapy
Pemetrexed/Carboplatin as chemotherapy
Carboplatin/Paclitaxel, as chemotherapy
DRUGVolrustomig
Participants will receive Volrustomig via intravenous route.
DRUGRilvegostomig
Participants will receive Rilvegostomig via intravenous route.
Sponsors
AstraZeneca
Parexel
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 95 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of participants with pathological complete response (pCR) | From randomization to approximately 15 weeks after the first dose of study interventions |
| Number of participants with adverse events (AEs) and serious adverse events (SAEs) | Until Day 90 after the last dose of study interventions (Up to approximately 3 years) |
Secondary
| Measure | Time frame |
|---|---|
| Number of participants experiencing an event-free survival (EFS) event | Up to approximately 3 years |
| Number of participants experiencing a disease-free survival (DFS) event | Up to approximately 3 years |
| Number of participants having surgical resection | From randomization to approximately 15 weeks after the first dose of study interventions |
| Number of participants with major pathological response (mPR) | From randomization to approximately 15 weeks after the first dose of study interventions |
| Number of participants with Objective response rate (ORR) | From randomization to approximately 15 weeks after the first dose of study interventions |
| Overall survival (OS) | Up to approximately 3 years |
| Serum concentration of study interventions (Durvalumab/Oleclumab/Monalizumab/Volrustomig/Rilvegostomig) | From randomization to last dose of study interventions (Up to approximately 3 Years) |
| Number of participants with anti-study drug antibodies (ADA) | From randomization to 3 months after last dose of study interventions (Up to approximately 3 Years) |
| Baseline PD-L1 expression | At Screening/ baseline |
| Changes in circulating tumour DNA (ctDNA) | From randomization to up to 24 months after last dose of study interventions (Up to approximately 3 Years) |
Countries
Belgium, Canada, France, Hungary, Ireland, Italy, Portugal, South Korea, Spain, Taiwan, Turkey (Türkiye), United States
Contacts
CONTACTAstraZeneca Clinical Study Information Center
CONTACTAstraZeneca Lung Cancer Study Locator Service
PRINCIPAL_INVESTIGATORTina Cascone, MD
MD Anderson Cancer Center Houston, TX 77030
Outcome results
None listed