A Study of Neoadjuvant/Adjuvant Durvalumab for the Treatment of Patients With Resectable Non-small Cell Lung Cancer
Phase 3
Active, not recruiting
- Conditions
- Non-Small Cell Lung Cancer
- Interventions
- Other: PlaceboProcedure: Surgery
- Registration Number
- NCT03800134
- Lead Sponsor
- AstraZeneca
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ACTIVE_NOT_RECRUITING
- Sex
- All
- Target Recruitment
- 825
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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Durvalumab with platinum-based chemotherapy Surgery Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 2: Placebo with platinum-based chemotherapy Placebo Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 2: Placebo with platinum-based chemotherapy Surgery Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 1: Durvalumab with platinum-based chemotherapy Durvalumab Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 1: Durvalumab with platinum-based chemotherapy Carboplatin Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 1: Durvalumab with platinum-based chemotherapy Cisplatin Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 1: Durvalumab with platinum-based chemotherapy Pemetrexed Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 1: Durvalumab with platinum-based chemotherapy Gemcitabine Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 1: Durvalumab with platinum-based chemotherapy Paclitaxel Patients will receive durvalumab 1500 mg in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by durvalumab 1500 mg monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 2: Placebo with platinum-based chemotherapy Cisplatin Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 2: Placebo with platinum-based chemotherapy Carboplatin Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 2: Placebo with platinum-based chemotherapy Pemetrexed Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 2: Placebo with platinum-based chemotherapy Gemcitabine Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment) Arm 2: Placebo with platinum-based chemotherapy Paclitaxel Patients will receive placebo in combination with platinum-based chemotherapy every 3 weeks for up to 4 cycles prior to surgery, followed by placebo monotherapy every 4 weeks for up to 12 cycles after surgery unless disease is deemed unresectable, disease recurrence, or unacceptable toxicity The platinum-based chemotherapy will be based on tumour histology and Investigator discretion: * cisplatin with pemetrexed * carboplatin with pemetrexed * carboplatin with paclitaxel * cisplatin with gemcitabine (or carboplatin with gemcitabine for patients who have comorbidities or who are unable to tolerate cisplatin per the investigator's judgment)
- Primary Outcome Measures
Name Time Method 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.
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.
- Secondary Outcome Measures
Name Time Method 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.
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 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.
Disease-free survival (DFS) in modified resected population From date of randomization to approximately 5.5 years after date of resection 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 the PK of durvalumab in blood From date of randomization to 2 months after resection To assess concentration of durvalumab in bloodstream.
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 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. 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.
Trial Locations
- Locations (1)
Research Site
🇻🇳Ho Chi Minh, Vietnam