A Study of Atezolizumab Compared With a Single-Agent Chemotherapy in Treatment Naïve Participants With Locally Advanced or Recurrent or Metastatic Non-Small Cell Lung Cancer Who Are Deemed Unsuitable For Platinum-Doublet Chemotherapy

• Register: ClinicalTrials.gov
• Last refreshed on: 13 November 2023
• Main ID: NCT03191786
• Date of registration: 15/06/2017
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study of Atezolizumab Compared With a Single-Agent Chemotherapy in Treatment Naïve Participants With Locally Advanced or Recurrent or Metastatic Non-Small Cell Lung Cancer Who Are Deemed Unsuitable For Platinum-Doublet Chemotherapy IPSOS
• Scientific title: A Phase III, Open-Label, Multicenter, Randomized Study to Investigate the Efficacy and Safety of Atezolizumab Compared With Chemotherapy in Patients With Treatment Naïve Advanced or Recurrent (Stage IIIb Not Amenable for Multimodality Treatment) or Metastatic (Stage IV) Non-Small Cell Lung Cancer Who Are Deemed Unsuitable for Platinum-Containing Therapy
• Date of first enrolment: September 11, 2017
• Target sample size: 453
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/ct2/show/NCT03191786
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 3

Countries of recruitment

Argentina, Belgium, Brazil, Bulgaria, Canada, China, Colombia, Czechia, Denmark, Germany, India, Ireland, Italy, Kazakhstan, Luxembourg, Mexico, Poland, Portugal, Romania, Slovakia, Spain, Swaziland, Switzerland, United Kingdom, Vietnam

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

- Histologically or cytologically confirmed diagnosis of advanced or recurrent (Stage
IIIB not amenable for multimodality treatment) or metastatic (Stage IV) NSCLC as per
the American Joint Committee on Cancer (AJCC) 7th edition

- No sensitizing epidermal growth factor receptor (EGFR) mutation (L858R or exon 19
deletions) or anaplastic lymphoma kinase (ALK) fusion oncogene detected

- No prior systemic treatment for advanced or recurrent (Stage IIIB not amenable for
multimodality treatment) or metastatic (Stage IV) NSCLC as per the AJCC 7th edition

- Life expectancy greater than or equal to (>/=) 8 weeks

- Deemed unsuitable by the investigator for any platinum-doublet chemotherapy due to
poor performance status (ECOG performance status of 2-3). However, participants >= 70
years of age who have an ECOG PS of 0 or 1 may be included due to: a) substantial
comorbidities; b) contraindication(s) for any platinum-doublet chemotherapy

- Representative formalin-fixed paraffin-embedded (FPPE) tumor tissue block obtained
during course of disease (archival tissue) or at screening

- Participants with treated, asymptomatic central nervous system (CNS) metastases are
eligible, provided they meet all of the following criteria: Measurable disease outside
CNS; Only supratentorial and cerebellar metastases allowed; No ongoing requirement for
corticosteroids as therapy for CNS disease; No stereotactic radiation within 7 days or
whole-brain radiation within 14 days prior to randomization; No evidence of interim
progression between the completion of CNS-directed therapy and the screening
radiographic study

- Adequate hematologic and end organ function

- Female participants of childbearing potential randomized to the atezolizumab treatment
arm agree to use protocol defined methods of contraception

Exclusion Criteria:

Cancer-Specific Exclusion Criteria:

- Participants younger than 70 years who have an ECOG performance status of 0 or 1

- Active or untreated CNS metastases as determined by computed tomography (CT) or
magnetic resonance imaging (MRI) evaluation of the brain during screening and prior
radiographic assessments

- Uncontrolled tumor-related pain

- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently)

- Uncontrolled or symptomatic hyerpcalcemia (ionized calcium > 1.5 mmol/L or calcium >12
mg/dL or corrected serum calcium >ULN)

- History of other malignancy within 5 years prior to screening, with the exception of
those with a negligible risk of metastasis or death treated with expected curative
outcome

- National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)
version 4.0 (v4.0) Grade 3 or higher toxicities due to any prior therapy (example
[e.g.], radiotherapy) (excluding alopecia), which have not shown improvement and are
strictly considered to interfere with current study medication

- Participants who have received prior neo-adjuvant, adjuvant chemotherapy,
radiotherapy, or chemoradiotherapy with curative intent for non-metastatic disease
must have experienced a treatment-free interval of at least 6 months from
randomization since the last chemotherapy, radiotherapy, or chemoradiotherapy

General Medical Exclusion Criteria:

- History of autoimmune disease except autoimmune-related hypothyroidism and controlled
Type I diabetes mellitus

- History of idiopathic pulmonary fibrosis (IPF), organizing pneumonia (e.g.,
bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or
evidence of active pneumonitis

- Known positivity for human immunodeficiency virus (HIV)

- Known active hepatitis B or hepatitis C

- Active tuberculosis

- Severe infections within 4 weeks prior to randomization

- Significant cardiovascular disease, such as New York Heart Association (NYHA) cardiac
disease (Class II or greater), myocardial infarction within 3 months prior to
randomization, unstable arrhythmias, or unstable angina

- Major surgical procedure other than for diagnosis within 4 weeks prior to
randomization or anticipation of need for a major surgical procedure during the course
of the study

- Prior allogeneic bone marrow transplantation or solid organ transplant

- Participants with an illness or condition that may interfere with capacity or
compliance with the study protocol, as per investigator's judgment

- Treatment with any other investigational agent or participation in another clinical
study with therapeutic intent within 28 days prior to randomization

Exclusion Criteria Related to Atezolizumab:

- History of severe allergic, anaphylactic, or other hypersensitivity reactions to
chimeric or humanized antibodies or fusion proteins

- Known hypersensitivity to biopharmaceuticals produced in Chinese hamster ovary cells
or any component of the atezolizumab formulation

- Oral or IV antibiotic treatment

- Administration of a live, attenuated vaccine within 4 weeks before randomization or
anticipation that such a live attenuated vaccine will be required during the study

- Prior treatment with cluster of differentiation 137 (CD137) agonists or immune
checkpoint blockade therapies, anti-programmed death-1 (anti-PD-1), and anti-PD-L1
therapeutic antibodies

- Treatment with systemic immunostimulatory agents within 4 weeks or 5 half-lives of the
drug, whichever is shorter, prior to randomization

- Treatment with systemic corticosteroids or other immunosuppressive medications

- Participants not willing to stop treatment with traditional herbal medicines

Exclusion Criteria Related to Chemotherapy:

- Known sensitivity and contraindications to the 2 comparative chemotherapy agents (that
is [i.e.] vinorelbine, oral or intravenous, and gemcitabine, intravenous)



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Non-Small Cell Lung Cancer

Intervention(s)

Drug: Gemcitabine

Drug: Atezolizumab (MPDL3280A), an engineered anti-PD-L1 antibody

Drug: Vinorelbine

Primary Outcome(s)

Overall Survival (OS) [Time Frame: From randomization up to death from any cause (up to approximately 55 months)]

Secondary Outcome(s)

OS Rates at the 6, 12, 18, 24-Months Timepoints [Time Frame: 6, 12, 18 and 24 months]

Percentage of Participants With Objective Response Rate, as Determined by the Investigator Using Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 (v1.1) [Time Frame: From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)]

Time to Deterioration (TTD) in Patient-Reported Lung Cancer Symptoms as Assessed by EORTC QLQ-C30 Score [Time Frame: From baseline up to approximately 55 months]

Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1 [Time Frame: From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)]

Change From Baseline in EORTC QLQ Supplementary Lung Cancer Module 13 (EORTC QLQ-LC13) Score [Time Frame: Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days)]

Percentage of Participants With At Lease One Adverse Event [Time Frame: From randomization up to approximately 55 months]

Time to Deterioration in Patient-Reported Lung Cancer Symptoms As Assessed by EORTC QLQ-LC13 Score [Time Frame: From baseline up to approximately 55 months]

Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - Core 30 (EORTC-QLQ-C30) Score [Time Frame: Baseline, Day 1 of each treatment cycle up to 30 days after last dose (up to approximately 55 months) (Cycle length = 21 days)]

Duration of Response (DOR), as Determined by the Investigator Using RECIST v1.1 [Time Frame: Time from the first occurrence of a documented objective response to the time of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)]

Overall Survival in Participants With PD-L1 Positive Status [Time Frame: From randomization up to death from any cause (up to approximately 55 months)]

Progression-Free Survival (PFS), as Determined by the Investigator Using RECIST v1.1 in Participants With PD-L1 Positive Status [Time Frame: From randomization to the first occurence of disease progression or death from any cause, whichever occurs first (up to approximately 55 months)]

Secondary ID(s)

MO29872

2015-004105-16

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 17/05/2023
• URL: https://clinicaltrials.gov/ct2/show/results/NCT03191786