Safety and efficacy of MPDL3280A (anti-PDL1 antibody) compared to gemcitabine + platinum-based chemotherapy in previously untreated patients with metastatic, squamous, PD-L1-selected, non-small cell lung cancer

Phase 1

• Conditions: Previously untreated Stage IV, Squamous, Non-Small Cell Lung Cancer; MedDRA version: 20.0Level: PTClassification code 10025125Term: Lung squamous cell carcinoma stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-003106-33-IT
• Lead Sponsor: F. HOFFMANN - LA ROCHE LTD.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2018-12-10
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 400

Inclusion Criteria

•ECOG performance status of 0 or 1
•Histologically or cytologically confirmed, Stage IV squamous NSCLC
•Tumor PD-L1 expression as determined by an 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
•Patient with a history of treated asymptomatic CNS metastases are eligible, provided they meet all of the following criteria:
Measurable disease outside CNS
Only supratentorial metastases allowed (i.e., no metastases to midbrain, pons, medulla or spinal cord)
No ongoing requirement for corticosteroids as therapy for CNS disease;
anticonvulsants at a stable dose allowed
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
•Patients with new asymptomatic CNS metastases detected at the screening scan must receive radiation therapy and/or surgery for CNS metastases. Following treatment, these patients may then be eligible without the need for an additional brain scan prior to enrollment, if all other criteria are met.
•For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use a highly effective form(s) of contraception and to continue its use for 90 days after the last dose of MPDL3280A
•Women who are not postmenopausal (12 months of non-therapy- induced amenorrhea) or surgically sterile must have a negative serum pregnancy test result within 14 days prior to initiation of study drug.

Are the trial subjects under 18? no
Number of subjects for this age range: 1
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 280
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 120

Exclusion Criteria

•Active or untreated CNS metastases as determined by CT or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
•Leptomeningeal disease
•Uncontrolled tumor-related pain
•Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures
•Uncontrolled or symptomatic hypercalcemia
•Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death
•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 MPDL3280A formulation
•History of autoimmune disease, including but not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, multiple sclerosis, vasculitis, or glomerulonephritis
•History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening chest CT scan
•Positive test for HIV
•Patients with active hepatitis B or hepatitis C
•Active tuberculosis
•Severe infections within 4 weeks prior to randomization, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
•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
•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
Influenza vaccination should be given during influenza season. Patients must not receive live, attenuated influenza vaccine (e.g., FluMist?) within 4 weeks prior to randomization or at any time during the study.
•Any approved anti-cancer therapy, including chemotherapy, or hormonal therapy within 3 weeks prior to initiation of study treatment
•Treatment with any other investigational agent or participation in another clinical trial with therapeutic intent within 28 days prior to randomization

Study & Design

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