Carcinoma, Non-Small Cell Lung
Conditions
Brief summary
This is a Phase II, multicenter, double-blind, randomized study designed to evaluate the efficacy and safety of adjuvant treatment with atezolizumab in combination with platinum-doublet chemotherapy followed by atezolizumab compared with adjuvant placebo in combination with platinum-doublet chemotherapy followed by placebo in patients with Stage IB to IIIB (T3N2) NSCLC following surgical resection who are positive for ctDNA.
Interventions
DRUGAtezolizumab
Atezolizumab will be administered intravenously during the induction phase and the maintenance phase.
DRUGPlacebo
Placebo will be administered intravenously during the induction phase and the maintenance phase.
DRUGCarboplatin
Carboplatin will be administered intravenously during the induction phase.
DRUGCisplatin
Cisplatin will be administered intravenously during the induction phase.
DRUGPemetrexed
Pemetrexed will be administered intravenously during the induction phase.
DRUGGemcitabine
Gemcitabine will be administered intravenously during the induction phase.
DRUGPaclitaxel
Paclitaxel will be administered intravenously during the induction phase.
Sponsors
Hoffmann-La Roche
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Complete resection (R0) and pathologically confirmed Stage IB to select IIIB NSCLC (8th edition) * Submission of pre-surgery blood sample and surgically resected tumor tissue slides or block * Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 * Normal life expectancy excluding lung cancer mortality risk * Positive ctDNA status in plasma confirmed by central laboratory testing after surgical resection and prior to start of adjuvant therapy.
Exclusion criteria
* Resected NSCLC with positive margins (R1 or R2) * NSCLC with histology of large cell neuroendocrine carcinoma or sarcomatoid carcinoma * Mixed NSCLC and SCLC histology * Any prior therapy for lung cancer, including neoadjuvant therapy, or radiotherapy * NSCLC with an activating EGFR mutation or ALK fusion oncogene * Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| ctDNA Clearance Rate at 6 Months | Randomization up to 6 months | ctDNA clearance rate at 6 months after randomization, defined as the proportion of participants with undetectable ctDNA at 6 months in the post-operative ctDNA+ participants. |
| Disease-Free Survival (DFS) | Randomization up to approximatly 159 months | Disease-free survival (DFS), as assessed by the investigator, and defined as the time from randomization to the date of occurrence of any of the following, whichever occurs first: First documented local or distant recurrence of non-small cell lung cancer (NSCLC) after an integrated assessment of radiographic data, biopsy sample results (if available), and clinical status; Occurrence of new primary NSCLC (non-small cell lung cancer); Death from any cause in the post-operative ctDNA+ participants |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Duration of ctDNA Clearance | Up to approximatly 159 months | Duration of ctDNA clearance, defined as the time from the first documented ctDNA clearance to ctDNA detection, investigator-assessed radiographic or biopsy confirmed disease recurrence, or death from any cause, whichever occurs first in post-operative ctDNA+ participants. |
| Overall survival (OS) | Randomization to death from any cause (up to approximately 159 months) | Overall survival (OS) after randomization, defined as the time from randomization to death from any cause in the post-operative ctDNA+ participants. |
| DFS Rate | Randomization to 2 years and 3 years | DFS rate at 2 years and 3 years, defined as the probability that a participant has not experienced disease recurrence, a new primary NSCLC, or death from any cause, as determined by the investigator at 2 years and 3 years, respectively in the post-operative ctDNA+ participants. |
| ctDNA Clearance Rate at 12 Months | Randomization up to 12 months | ctDNA clearance rate in post-operative ctDNA+ participants. |
| OS Rate | Randomization to 2 years and 3 years | OS rate at 2 years and 3 years, defined as the probability that a patient has not experienced death from any cause at 2 years and 3 years, respectively in the post-operative ctDNA+ participants. |
| Time to Confirmed Deterioration (TTCD) in Patient-Reported Functioning and Global Health (GHS)/Quality of Life (QoL) | Up to approximately 159 months | Time to confirmed deterioration (TTCD) in patient-reported functioning and global health (GHS)/quality of life (QoL), as measured by the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30), and in patient-reported lung cancer symptoms for cough, dyspnea (a multi-item subscale), and chest pain, as measured through the use of the EORTC Quality-of-Life Questionnaire Lung Cancer Module (QLQ-LC13) in the post-operative ctDNA+ participants. |
| Percentage of Pariticipants with Adverse Events | Randomization up to approximatly 159 months | Percentage of participants with adverse events in the post-operative ctDNA+ participants. |
| Overall ctDNA Clearance Rate in the PD-L1 TC>=1% Population | Randomization up to approximately 159 months | Overall ctDNA clearance rate in the PD-L1 TC\>=1% (Ventana SP263) population in the post-operative ctDNA+ participants. |
| Overall ctDNA Clearance Rate | Randomization up to approximately 159 months | Overall ctDNA clearance rate in post-operative ctDNA+ participants. |
Outcome results
None listed