A Study Evaluating the Efficacy and Safety of Adjuvant Platinum-Doublet Chemotherapy, With or Without Atezolizumab, in Patients Who Are ctDNA Positive After Complete Surgical Resection of Stage IB to Select IIIB Non-Small Cell Lung Cancer

Study Overview
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Brief Summary
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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.

Official Title
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A Phase II, Randomized, Double-Blind, Placebo-Controlled Study Evaluating the Efficacy and Safety of Adjuvant Platinum-Doublet Chemotherapy, With or Without Atezolizumab, in Patients Who Are ctDNA Positive After Complete Surgical Resection of Stage IB to Select IIIB Non-Small Cell Lung Cancer

Conditions
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Carcinoma, Non-Small Cell Lung

Intervention / Treatment
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* Drug: Atezolizumab
* Drug: Placebo
* Drug: Carboplatin
* Drug: Cisplatin
* Drug: Pemetrexed
* Drug: Gemcitabine
* Drug: Paclitaxel


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm A: Atezolizumab + platinum-doublet followed by atezolizumab maintenance<br> | Drug: Atezolizumab<br>* Atezolizumab will be administered intravenously during the induction phase and the maintenance phase.<br>* Other names: Tecentriq;Drug: Carboplatin<br>* Carboplatin will be administered intravenously during the induction phase.<br>Drug: Cisplatin<br>* Cisplatin will be administered intravenously during the induction phase.<br>Drug: Pemetrexed<br>* Pemetrexed will be administered intravenously during the induction phase.<br>Drug: Gemcitabine<br>* Gemcitabine will be administered intravenously during the induction phase.<br>Drug: Paclitaxel<br>* Paclitaxel will be administered intravenously during the induction phase.<br>|
| Placebo Comparator: Arm B: Placebo + platinum-doublet followed by placebo maintenance<br> | Drug: Placebo<br>* Placebo will be administered intravenously during the induction phase and the maintenance phase.<br>Drug: Carboplatin<br>* Carboplatin will be administered intravenously during the induction phase.<br>Drug: Cisplatin<br>* Cisplatin will be administered intravenously during the induction phase.<br>Drug: Pemetrexed<br>* Pemetrexed will be administered intravenously during the induction phase.<br>Drug: Gemcitabine<br>* Gemcitabine will be administered intravenously during the induction phase.<br>Drug: Paclitaxel<br>* Paclitaxel will be administered intravenously during the induction phase.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ctDNA Clearance Rate at 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. | Randomization up to 6 months | 
| Disease-Free Survival (DFS) | 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 | Randomization up to approximatly 159 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ctDNA Clearance Rate at 12 Months | ctDNA clearance rate in post-operative ctDNA+ participants. | Randomization up to 12 months | 
| Overall ctDNA Clearance Rate | Overall ctDNA clearance rate in post-operative ctDNA+ participants. | Randomization up to approximately 159 months | 
| Duration of ctDNA Clearance | 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. | Up to approximatly 159 months | 
| Overall survival (OS) | Overall survival (OS) after randomization, defined as the time from randomization to death from any cause in the post-operative ctDNA+ participants. | Randomization to death from any cause (up to approximately 159 months) | 
| DFS Rate | 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. | Randomization to 2 years and 3 years | 
| Overall ctDNA Clearance Rate in the PD-L1 TC>=1% Population | Overall ctDNA clearance rate in the PD-L1 TC>=1% (Ventana SP263) population in the post-operative ctDNA+ participants. | Randomization up to approximately 159 months | 
| OS Rate | 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. | Randomization to 2 years and 3 years | 
| Time to Confirmed Deterioration (TTCD) in Patient-Reported Functioning and Global Health (GHS)/Quality of Life (QoL) | 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. | Up to approximately 159 months | 
| Percentage of Pariticipants with Adverse Events | Percentage of participants with adverse events in the post-operative ctDNA+ participants. | Randomization up to approximatly 159 months |