Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer
Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer
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; or MEDI5752 in combination with platinum doublet chemotherapy or datopotamab
deruxtecan (Dato-DXd) in combination with durvalumab and single agent platinum chemotherapy
in participants with resectable, early-stage non-small cell lung cancer.
Durvalumab in combination with Oleclumab, Monalizumab or AZD0171 and platinum doublet
chemotherapy; or MEDI5752 in combination with platinum doublet chemotherapy or datopotamab
deruxtecan (Dato-DXd) in combination with durvalumab and single agent platinum chemotherapy
in participants with resectable, early-stage non-small cell lung cancer.
Lung
Phase II
Adults
Chemotherapy - cytotoxic,
Mol. targeted/Immunotherapy/Biologics
AZD0171,
Carboplatin,
Cisplatin,
Dato-DXd,
Durvalumab,
Monalizumab,
Oleclumab,
Paclitaxel,
Pemetrexed,
Rilvegostomig,
Volrustomig (MEDI5752)
Lovly, Christine
International
Vanderbilt University
10-23-2023
Eligibility
18 Years
BOTH
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.
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.
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.
