Non-Small-Cell Lung
Conditions
Brief summary
This is a randomized, double-blinded study designed to evaluate the efficacy, safety, pharmacokinetics, and immunogenicity of neoadjuvant treatment with atezolizumab (MPDL3280A) or placebo in combination with platinum-based chemotherapy in participants with resectable Stage II, IIIA, or select IIIB non-small cell lung cancer (NSCLC) followed by open-label adjuvant/postoperative atezolizumab or best supportive care and monitoring.
Interventions
Atezolizumab will be administered as intravenous (IV) infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle (every 3 weeks) for 4 cycles during the neoadjuvant treatment phase Atezolizumab will be administered as IV infusion at a dose of 1200 milligrams (mg) every 3 weeks for 16 cycles during the post-operative adjuvant phase
DRUGPlacebo Comparator
Placebo will be administered as IV infusion at a dose of 1200 milligrams (mg) on Day 1 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
DRUGNab-paclitaxel
Nab-paclitaxel 100 mg/m\^2 will be administered intravenously on Days 1, 8, and 15 of each 21 day cycle for 4 cycles during the neoadjuvant treatment phase
DRUGPemetrexed
Pemetrexed 500 mg/m\^2 will be administered intravenously on Day 1 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
DRUGCarboplatin
Carboplatin initial target AUC of 6 mg/mL/min will be administered intravenously on Day 1 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
DRUGCisplatin
Cisplatin 75 mg/m\^2 will be administered intravenously on Day 1 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
DRUGGemcitabine
Gemcitabine 1250 mg/m\^2 will be administered intravenously on Day 1 and 8 of each 21-day cycle for 4 cycles during the neoadjuvant treatment phase
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Eastern Cooperative Oncology Group (ECOG) performance status 0 or 1 * Histologically or cytologically confirmed, resectable Stage II, IIIA, or Select IIIB (T3N2 only) NSCLC of squamous or non-squamous histology. Staging should be based on the 8th edition of the AJCC/UICC staging system * Evaluation by an attending thoracic surgeon to confirm eligibility for an R0 resection with curative intent * Adequate pulmonary and cardiac function to undergo surgical resection * Measurable disease as defined by RECIST v1.1 * Adequate hematologic and end organ function * Negative HIV test at screening * Negative for active HBV and HCV at screening * Adequate tissue for PD-L1 IHC assessment
Exclusion criteria
* NSCLC with histology of large cell neuroendocrine carcinoma or sarcomatoid carcinoma * Mixed NSCLC and small cell lung cancer histology * Any prior therapy for lung cancer * Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated expected curative outcome * Non-squamous NSCLC histology with activating ALK and EGFR mutation * Pregnant or lactating women * History of autoimmune disease * History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, or evidence of active of active pneumonitis on screening chest Computed Tomography (CT) scan * Prior treatment with cluster of differentiation 137 (CD137) agonist or immune checkpoint blockade therapies, anti-programmed-death-1 (anti-PD-1), and anti-PD-L1 therapeutic antibody * Severe infection within 4 weeks prior to randomization * Significant history of cardiovascular disease
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Independent Review Facility (IRF)-Assessed Event Free Survival (EFS) | Up to approximately 96 months | IRF-assessed EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, or death from any cause, whichever occurs first. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pathological Complete Response (pCR) | At time of surgery | pCR is defined as the absence of any viable primary tumor cells at the time of surgical resection in the primary tumor and all sampled lymph nodes as assessed by central and local pathology laboratory. |
| Major Pathological Response (MPR) | At time of surgery | MPR is defined as ≤ 10% residual viable tumor cells at the time of surgical resection in the primary tumor, as assessed by central and local pathology laboratory. |
| Objective Response (OR) | Prior to surgery, up to approximately 84 days | Objective response is defined as a complete response or partial response, as determined by the investigator according to RECIST v1.1 |
| Overall Survival (OS) | Up to approximately 96 months | OS is defined as the time from randomization to death from any cause during the course of the study. |
| Investigator-Assessed EFS | Up to approximately 96 months | EFS is defined as the time from randomization to the first documented disease progression per RECIST v1.1 that precludes surgery, local or distant disease recurrence, as assessed by the investigator; or death from any cause, whichever occurs first. |
| Disease-Free Survival (DFS) | Up to approximately 96 months | DFS is defined as the time from the first date of no disease to local or distant recurrence (including occurrence of new primary NSCLC) or death due to any cause, whichever occurs first, as determined by the investigator during the adjuvant treatment and observation follow-up |
| 2-Year and 3-Year OS | Up to approximately 96 months | The 2-year and 3-year OS rate is defined as the probability that a participant will be alive 2 years and 3 years after randomization, respectively. |
| 2-Year and 3-Year Independent Review Facility-Assessed EFS | Up to approximately 96 months | EFS is defined as the probability that a participant will be event-free 2 years and 3 years after randomization, respectively, as assessed by the Independent Review Facility. |
| 2-Year and 3-Year Investigator-Assessed EFS | Up to approximately 96 months | EFS is defined as the probability that a participant will be event-free 2 years and 3 years after randomization, respectively, as assessed by the Investigator. |
| Change from baseline in HRQoL scores | Up to approximately 96 months | Change from baseline in HRQoL scores as assessed through use of the two-item GHS/HRQoL subscale (Questions 29 and 30) of the EORTC QLQ-C30 at each assessment time point during the study through the completion of adjuvant treatment and observation follow-up assessments |
| Percentage of Participants With Adverse Events (AEs) | Up to approximately 96 months | — |
| Number and Severity of Surgical Related Adverse Events | Up to approximately 96 months | — |
| Number of Surgical Delays | Up to approximately 96 months | Number of surgical delays. |
| Length of Surgical Delays | Up to approximately 96 months | Length of surgical delays. |
| Number of Operative and Post-Operative Complications | Up to approximately 96 months | Number of operative and post-operative complications. |
| Reasons for Surgical Cancellations | Up to approximately 96 months | Reasons for surgical cancellations. |
| Minimum Observed Serum Atezolizumab Concentration (Cmin) | Pre-dose on Day 1 of Cycles 1 and 3 (each cylce is 21 days) for Neoadjuvant Treatment; pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 (each cycle is 21 days) for Arm A; at treatment or observation follow-up discontinuation (up to approximately 96 months) | Cmin is the minimum (or trough) concentration that a study drug achieves in the body. |
| Maximum Observed Serum Atezolizumab Concentration (Cmax) | Pre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 96 months) | Cmax is the maximum (or peak) concentration that a study drug achieves in the body. |
| Percentage of Participants With Anti-Drug Antibody (ADA) to Atezolizumab | Pre-dose on Day 1 of Cycles 1 and 3 for Neoadjuvant Treatment; Pre-dose on Day 1 of Cycles 5, 7, 9, 11 and 19 for Arm A. Each cycle is 21 days; at treatment or observation follow-up discontinuation (up to approximately 96 months) | — |
Countries
Australia, Austria, Brazil, China, France, Germany, Hungary, Israel, Italy, Japan, Poland, Russia, Serbia, Slovenia, South Africa, South Korea, Spain, Sweden, Switzerland, Taiwan, Thailand, Ukraine, United Kingdom, United States
Contacts
STUDY_DIRECTORClinical Trials
Hoffmann-La Roche
Outcome results
None listed