A Study of Atezolizumab (MPDL3280A, Anti-Pd-L1 Antibody) in Combination with Carboplatin or Cisplatin + Pemetrexed Compared with Carboplatin or Cisplatin + Pemetrexed in Patients who are Chemotherapy-Naive and have Stage IV Non-Squamous Non-Small Cell Lung Cancer

Phase 1

• Conditions: Metastatic non-squamous non-small cell lung cancer; MedDRA version: 19.0Level: LLTClassification code 10029514Term: Non-small cell lung cancer NOSSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-003605-42-FR
• Lead Sponsor: F. Hoffmann-La Roche Ltd

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-06-09
• Last Update Posted: 7 September 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 578

Inclusion Criteria

- Male or female, 18 years of age or older
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
- Histologically or cytologically confirmed, Stage IV non-squamous NSCLC
- No prior treatment for Stage IV non-squamous NSCLC
- Patients who have received prior neo-adjuvant, adjuvant chemotherapy, 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 or completion of chemoradiotherapy
- Known PD-L1 tumor status as determined by an immunohistochemistry (IHC) assay performed by a central laboratory on previously obtained archival tumor tissue or tissue obtained from a biopsy at screening
- Measurable disease, as defined by RECIST v1.1
- Adequate hematologic and end organ function
- For women of childbearing potential: agreement to remain abstinent or use contraceptive methods that result in a failure rate of < 1% per year during the treatment period and for at least 90 days after the last dose of study treatment
- For men: agreement to remain abstinent or use contraceptive measures and agreement to refrain from donating sperm

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 374
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 306

Exclusion Criteria

Cancer-Specific Exclusions
- Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
- Spinal cord compression not definitively treated with surgery and/or radiation or previously diagnosed and treated spinal cord compression without evidence that disease has been clinically stable for >= 2 weeks prior to randomization
- Leptomeningeal disease
- Uncontrolled tumor-related pain
- Uncontrolled or symptomatic hypercalcemia (> 1.5 millimole/Liter ionized calcium or calcium > 12 milligram/deciliter or corrected serum calcium > upper limit of normal)
- Malignancies other than non-small cell lung cancer (NSCLC) within 5 years prior to randomization
- Known tumor PD-L1 expression status from other clinical studies (e.g., patients whose PD-L1 expression status was determined during screening for entry into a study with anti-PD-1 or anti-PD L1 antibodies but were not eligible are excluded)
General Medical Exclusions:
- History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins
- History of certain autoimmune disease
- History of idiopathic pulmonary fibrosis, organizing pneumonia, drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis
- Severe infections within 4 weeks prior to randomization
- Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 3 months prior to randomization, unstable arrhythmias, or unstable angina

Exclusion Criteria Related to Medications and Chemotherapy:
- Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment
- Prior treatment with CD137 agonists or immune checkpoint blockade therapies, anti-PD-1, and anti-PD-L1 therapeutic antibodies
- Treatment with systemic immunostimulatory agents within 4 weeks prior to randomization
- Treatment with systemic immunosuppressive medications

Exclusion Criteria Related to Chemotherapy:
- History of allergic reactions to cisplatin, carboplatin, or other platinum-containing compounds
- Patients with hearing impairment (cisplatin)
- Grade >= 2 peripheral neuropathy as defined by National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v4.0 criteria (cisplatin)
- Creatinine clearance (CRCL) =< 60 milliliter (mL)/minute (min) for cisplatin or < 45 mL/min for carboplatin

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified