A Randomized, Phase 3, Open-Label Study of Combinations of REGN2810 (Anti-PD-1 Antibody), Platinum based Doublet Chemotherapy, and Ipilimumab (Anti-CTLA-4 Antibody) Versus Pembrolizumab Monotherapy in First-Line Treatment of Patients With Advanced or Metastatic Non-Small Cell Lung Cancer With Tumors Expressing PD-L1 >=50%
- Conditions
- 10029107lung cancerlung tumours10027656
- Registration Number
- NL-OMON46388
- Lead Sponsor
- Regeneron Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Suspended
- Sex
- Not specified
- Target Recruitment
- 20
1. Men and women >=18 years of age.
2. Patients with histologically or cytologically documented squamous or non-squamous NSCLC with stage IIIB disease who are not candidates for treatment with definitive concurrent chemoradiation or patients with stage IV disease if they have not received prior systemic treatment for recurrent or metastatic NSCLC.
3. Availability of an archival or on-study obtained formalin-fixed, paraffin embedded tumor tissue sample
4. Expression of PD L1 in >=50% of tumor cells determined by a commercially available assay.
5. At least 1 radiographically measureable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria. Target lesions may be located in a previously irradiated field if there is documented (radiographic) disease progression in that site.
6. ECOG performance status of <=1.
7. Anticipated life expectancy of at least 3 months.
1. Patients who have never smoked, defined as smoking <=100 cigarettes in a lifetime.
2. Active or untreated brain metastases or spinal cord compression. Patients are eligible if central nervous system (CNS) metastases are adequately treated and patients have neurologically returned to baseline (except for residual signs or symptoms related to the CNS treatment) for at least 2 weeks prior to enrollment. Patients must be off (immunosuppressive doses of) corticosteroid therapy (see exclusion criterion 7 for details on timing of discontinuation of corticosteroid therapy).
3. Patients with tumors tested positive for EGFR gene mutations, ALK gene translocations, or ROS1 fusions. All patients will have tumor evaluated for EGFR mutations, ALK rearrangement, and ROS1 fusions.
4. Encephalitis, meningitis, or uncontrolled seizures in the year prior to informed consent.
5. History of interstitial lung disease (eg, idiopathic pulmonary fibrosis or organizing
pneumonia), of active, noninfectious pneumonitis that required immune-suppressive
doses of glucocorticoids to assist with management, or of pneumonitis within the last
5 years. A history of radiation pneumonitis in the radiation field is permitted as long as
pneumonitis resolved >=6months prior to enrollment.
6. Ongoing or recent evidence of significant autoimmune disease that required treatment
with systemic immunosuppressive treatments, which may suggest risk of immune-related
treatment-emergent adverse events (irTEAEs). The following are not exclusionary:
vitiligo, childhood asthma that has resolved, residual hypothyroidism that required only
hormone replacement, or psoriasis that does not require systemic treatment.
7. Patients with a condition requiring corticosteroid therapy (>10 mg prednisone/day or
equivalent) within 14 days of randomization. Physiologic replacement doses are allowed
even if they are >10 mg of prednisone/day or equivalent, as long as they are not being
administered for immunosuppressive intent. Inhaled or topical steroids are permitted,
provided that they are not for treatment of an autoimmune disorder.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>The primary endpoint is PFS as assessed by a blinded Independent Review<br /><br>Committee (IRC) based on RECIST 1.1 assessments.</p><br>
- Secondary Outcome Measures
Name Time Method <p>The key secondary endpoints will be OS and ORR.<br /><br>Other secondary endpoints will include the following:<br /><br>• The safety and tolerability of REGN2810/ipi and REGN2810/chemo/ipi measured<br /><br>by the incidence of treatment-emergent adverse events (TEAEs), dose-limiting<br /><br>toxicities (DLTs), serious adverse events (SAEs), deaths, and laboratory<br /><br>abnormalities<br /><br>• Overall survival at 12 months and 18 months<br /><br>• Quality of life as measured by the European Organization for Research and<br /><br>Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and<br /><br>European Organization for Research and Treatment of Cancer Quality of Life<br /><br>Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)<br /><br>• Tumor mutation burden as assessed by the Foundation Medicine *FoundationOne®*<br /><br>panel, sample permitting</p><br>