Non-Small Cell Lung Cancer
Conditions
Keywords
Resectable Non-small Cell Lung Cancer, NSCLC, Carcinoma, Non-small Cell Lung Cancer
Brief summary
This is a Phase III, randomized, double-blind, placebo-controlled, multi-center international study assessing the activity of durvalumab and chemotherapy administered prior to surgery compared with placebo and chemotherapy administered prior to surgery in terms of pathological complete response.
Interventions
DRUGDurvalumab
1500mg on Day 1 of each 3-week cycle for 4 cycles during the neoadjuvant period and 1500mg on Day 1 of each 4-week cycle for 12 cycles during the adjuvant period
OTHERPlacebo
Day 1 of each 3-week cycle for 4 cycles during the neoadjuvant period and Day 1 of each 4-week cycle for 12 cycles during the adjuvant period
DRUGCarboplatin
Area under the curve of 5/6 on Day 1 of each 3-week cycle for 4 cycles
DRUGCisplatin
75 mg/m2 on Day 1 of each 3-week cycle, for 4 cycles
DRUGPemetrexed
500 mg/m2 on Day 1 of each 3-week cycle for 4 cycles.
DRUGPaclitaxel
200mg/m2 on Day 1 of each 3-week cycle for 4 cycles.
DRUGGemcitabine
1250 mg/m2 on Day 1 and Day 8 of each 3-week cycle, for 4 cycles.
PROCEDURESurgery
Expected within 40 days from the last dose of Investigational Product following the completion of neoadjuvant treatment.
Sponsors
AstraZeneca
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 120 Years
Healthy volunteers
No
Inclusion criteria
* Age ≥18 years * Newly diagnosed and previously untreated patients with histologically or cytologically documented NSCLC with resectable (Stage IIA to select \[ie, N2\] Stage IIIB) disease * World Health Organization (WHO)/ECOG PS of 0 or 1 at enrollment * At least 1 lesion, not previously irradiated, that qualifies as a RECIST 1.1 Target Lesion (TL) at baseline * No prior exposure to immune-mediated therapy including, but not limited to, other anti-CTLA-4, anti-PD-1, anti-PD-L1, and anti-PD-L2 antibodies, excluding therapeutic anticancer vaccines * Adequate organ and marrow function * Confirmation of a patient's tumour PD-L1 status * Provision of sufficient tumour biopsy sample for evaluation and confirmation of EGFR and ALK status * Planned surgery must comprise lobectomy, sleeve resection, or bilobectomy
Exclusion criteria
* History of allogeneic organ transplantation * Active or prior documented autoimmune or inflammatory disorders (including inflammatory bowel disease, diverticulitis, systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome) * History of another primary malignancy * History of active primary immunodeficiency * Active infection including tuberculosis hepatitis B and C, or human immunodeficiency virus * Deemed unresectable NSCLC by multidisciplinary evaluation * Patients who have pre-operative radiotherapy treatment as part of their care plan * Patients who have brain metastases or spinal cord compression * Stage IIIB N3 and Stages IIIC, IVA, and IVB NSCLC * Known allergy or hypersensitivity to any of the study drugs or excipients * Existence of more than one primary tumour such as mixed small cell and NSCLC histology * Patients whose planned surgery at enrollment includes any of the following procedures: pneumonectomy, segmentectomies, or wedge resections * Patients with a documented test result confirming the presence of EGFRm or ALK translocation
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Event-Free Survival (EFS) in modified intent to treat (mITT) population | Up to 5.5 years after first patient randomized. | An event is defined as documented RECIST 1.1 local or distant recurrence of lung cancer; death due to any cause; disease progression that precludes surgery or discovered upon attempting surgery that prevents completion of surgery. |
| Pathological Complete Response (pCR) in modified intent-to-treat (mITT) population | Up to approximately 15 weeks after randomization | Defined as the lack of any viable tumour cells after complete evaluation in the resected lung cancer specimen and all sampled regional lymph nodes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Disease-free survival (DFS) in modified resected population | From date of randomization to approximately 5.5 years after date of resection | — |
| Major Pathological Response (mPR) in modified intent to treat (mITT) population | Up to approximately 15 weeks after randomization | — |
| Overall Survival (OS) in modified intent to treat (mITT) population | From date of randomization to 5.5 years after randomization | — |
| Event-free survival (EFS) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population | From date of randomization to 5.5 years after randomization | — |
| pCR in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population | Up to approximately 15 weeks after randomization | — |
| Major Pathological Response (mPR) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population | Up to approximately 15 weeks after randomization | — |
| Overall Survival (OS) in PD-L1-TC ≥1% patients in modified intent to treat (mITT) population | From date of randomization to 5.5 years after randomization. | — |
| To assess disease-related symptoms and HRQoL (EORTC QLQ-LC13) in patients treated with durvalumab + chemotherapy prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy prior to surgery followed by placebo post-surgery | From date of screening to 6 months after last dose of IP | To assess disease-related symptoms, functioning, and global health status/quality of life in patients. |
| To assess the PK of durvalumab in blood | From date of randomization to 2 months after resection | To assess concentration of durvalumab in bloodstream. |
| Presence of ADA for durvalumab | From date of randomization to 3 months after last dose of IP | To evaluate the presence of antibodies following treatment with study medications. |
| Disease-Free Survival (DFS) in PD-L1-TC ≥1% patients in modified resected population | From date of randomization to 5.5 years after date of resection | — |
| To assess disease-related symptoms and HRQoL (EORTC QLQ-C30) in patients treated with durvalumab + chemotherapy prior to surgery followed by durvalumab post-surgery compared with placebo + chemotherapy prior to surgery followed by placebo post-surgery | From date of screening to 6 months after last dose of IP | To assess disease-related symptoms, functioning, and global health status/quality of life in patients. |
Other
| Measure | Time frame |
|---|---|
| Number of participants with adverse events as assessed by CTCAE v5.0 | From date of randomization to 3 months after last dose of IP |
Countries
Argentina, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, China, Costa Rica, France, Germany, Hungary, India, Italy, Japan, Mexico, Netherlands, Peru, Philippines, Poland, Romania, Russia, South Korea, Spain, Taiwan, Thailand, United States, Vietnam
Outcome results
None listed