Neoadjuvant and Adjuvant Treatment in Resectable Non-small Cell Lung Cancer
Purpose
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 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.
Condition
- Non-small Cell Lung Cancer
Eligibility
- Eligible Ages
- Between 18 Years and 95 Years
- Eligible Genders
- All
- Accepts 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. - 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.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Primary Purpose
- Treatment
- Masking
- None (Open Label)
Arm Groups
| Arm | Description | Assigned Intervention |
|---|---|---|
|
Experimental Arm 1: Oleclumab + Durvalumab + Platinum doublet chemotherapy (CTX) |
Participants will receive Durvalumab + Oleclumab + CTX as neoadjuvant treatment and Durvalumab + Oleclumab as adjuvant treatment. Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery: Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin |
|
|
Experimental Arm 2: Monalizumab + Durvalumab + CTX |
Participants will receive Durvalumab + Monalizumab + CTX as neoadjuvant treatment and Durvalumab + Monalizumab as adjuvant treatment. Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery: Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin |
|
|
Experimental Arm 3: Volrustomig (Dose Exploration) + CTX |
Participants will receive Volrustomig + CTX as neoadjuvant treatment and Volrustomig as adjuvant treatment. Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery: Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin |
|
|
Experimental Arm 4: Dato-DXd + durvalumab + single agent platinum |
Participants will receive Dato-DXd + durvalumab + single agent platinum as neoadjuvant treatment and durvalumab as adjuvant treatment. Participants will receive one of the following chemotherapy regimens, based on physician choice of as part of their treatment regimen prior to surgery: Carboplatin or Cisplatin |
|
|
Experimental Arm 5: AZD0171 + durvalumab + CTX |
Participants will receive AZD0171 + durvalumab + CTX as neoadjuvant treatment and AZD0171 + durvalumab as adjuvant treatment. Participants will receive one of the following chemotherapy regimens, based on the tumour histology and Investigator's discretion, as part of their treatment regimen prior to surgery: Carboplatin/Paclitaxel Pemetrexed/Cisplatin Pemetrexed/Carboplatin |
|
Recruiting Locations
Research Site
Little Rock, Arkansas 72205
Little Rock, Arkansas 72205
Research Site
Los Angeles, California 90095
Los Angeles, California 90095
Research Site
New Haven, Connecticut 06510
New Haven, Connecticut 06510
Research Site
Stuart, Florida 34994
Stuart, Florida 34994
Research Site
Chicago, Illinois 60637
Chicago, Illinois 60637
Research Site
Baltimore, Maryland 21231
Baltimore, Maryland 21231
Research Site
Boston, Massachusetts 02215
Boston, Massachusetts 02215
Research Site
Saint Louis Park, Minnesota 55426
Saint Louis Park, Minnesota 55426
Research Site
Buffalo, New York 14263
Buffalo, New York 14263
Research Site
Cleveland, Ohio 44195
Cleveland, Ohio 44195
Research Site
Pittsburgh, Pennsylvania 15212
Pittsburgh, Pennsylvania 15212
Research Site
Chattanooga, Tennessee 37404
Chattanooga, Tennessee 37404
Research Site
Memphis, Tennessee 38120
Memphis, Tennessee 38120
Research Site
Nashville, Tennessee 37203
Nashville, Tennessee 37203
Research Site
Nashville, Tennessee 37232
Nashville, Tennessee 37232
Research Site
Houston, Texas 77030
Houston, Texas 77030
Research Site
Houston, Texas 77090
Houston, Texas 77090
Research Site
Fairfax, Virginia 22031
Fairfax, Virginia 22031
Research Site
Seattle, Washington 98104
Seattle, Washington 98104
More Details
- NCT ID
- NCT05061550
- Status
- Recruiting
- Sponsor
- AstraZeneca
Study Contact
AstraZeneca Clinical Study Information Center1-877-240-9479
information.center@astrazeneca.com
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.