The primary objective of the study is to compare the progression-free survival (PFS) of REGN2810 (cemiplimab) plus ipilimumab combination therapy (hereinafter referred to as REGN2810/ipi) and REGN2810 plus 2 cycles only of platinum-based doublet…
ID
Source
Brief title
Condition
- Miscellaneous and site unspecified neoplasms benign
- Respiratory tract neoplasms
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary endpoint is PFS as assessed by a blinded Independent Review
Committee (IRC) based on RECIST 1.1 assessments.
Secondary outcome
The key secondary endpoints will be OS and ORR.
Other secondary endpoints will include the following:
• The safety and tolerability of REGN2810/ipi and REGN2810/chemo/ipi measured
by the incidence of treatment-emergent adverse events (TEAEs), dose-limiting
toxicities (DLTs), serious adverse events (SAEs), deaths, and laboratory
abnormalities
• Overall survival at 12 months and 18 months
• Quality of life as measured by the European Organization for Research and
Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) and
European Organization for Research and Treatment of Cancer Quality of Life
Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)
• Tumor mutation burden as assessed by the Foundation Medicine *FoundationOne®*
panel, sample permitting
Background summary
Lung cancer is one of the most commonly diagnosed cancers and is the leading
cause of cancer related mortality worldwide. Non-small cell lung cancer
(NSCLC) accounts for 80% to 85% of all lung cancers and is composed of several
histopathological subtypes, the most common of which are adenocarcinoma (40% to
60%) and squamous cell carcinoma (30%). The majority of patients with NSCLC
are found to have advanced cancer at the time of diagnosis. With chemotherapy,
these patients have a median overall survival (OS) of up to 12 to 18 months and
a 5-year survival rate of approximately 18%.
Systemic treatment with platinum based doublet regimens, with or without
maintenance treatment, has been, until recently, the standard first line
treatment for all patients with advanced NSCLC whose tumors do not have an
epidermal growth factor receptor (EGFR) mutation, an anaplastic lymphoma kinase
(ALK) mutation, or a c-ros oncogene 1 receptor tyrosine kinase (ROS1) fusion.
Despite initial treatment with platinum based doublet regimens, the disease
often progresses, and additional treatment options have been limited.
The hypothesis of this study is that REGN2810 and ipilimumab for up to 4 cycles
of combination therapy (REGN2810/ipi) or REGN2810 plus platinum-based doublet
chemotherapy for 2 cycles and ipilimumab for up to 4 cycles of combination
therapy (REGN2810/chemo/ipi) will prolong median progressive-free survival
(PFS) compared with standard-of-care pembrolizumab monotherapy in the first
line treatment of patients with advanced or metastatic NSCLC whose tumors
express PD L1 in >=50% of tumor cells.
Study objective
The primary objective of the study is to compare the progression-free survival
(PFS) of REGN2810 (cemiplimab) plus ipilimumab combination therapy (hereinafter
referred to as REGN2810/ipi) and REGN2810 plus 2 cycles only of platinum-based
doublet chemotherapy plus ipilimumab combination therapy (hereinafter referred
to as *REGN2810/chemo/ipi*) with standard-of-care pembrolizumab monotherapy in
the first line treatment of patients with advanced squamous or non-squamous
non-small cell lung cancer (NSCLC) whose tumors express programmed death ligand
1 (PD L1) in >=50% of tumor cells.
Study design
This is a phase 3, randomized, global, open-label, pivotal, study of the
efficacy and safety of REGN2810/ipi versus REGN2810/chemo/ipi versus
pembrolizumab monotherapy in patients with stage IIIB or stage IV squamous or
non squamous NSCLC whose tumors express PD L1 in >=50% of tumor cells and who
have received no prior systemic treatment for their advanced disease.
The study will consist of the following 3 periods: screening, treatment, and
follow-up.
Intervention
• Treatment Arm A: pembrolizumab monotherapy 200 mg Q3W for 108 weeks
• Treatment Arm B: REGN2810 350 mg Q3W for 108 weeks plus ipilimumab 50 mg Q6W
for up to 4 doses (REGN2810/ipi)
• Treatment Arm C: REGN2810 350 mg Q3W for 108 weeks plus platinum-based
doublet chemotherapy Q3W for 2 cycles and ipilimumab 50 mg Q6W for up to 4
doses (REGN2810/chemo/ipi)
Study burden and risks
This study is a randomized, open-label, phase 3 study evaluating the efficacy
of REGN2810/ipi or REGN2810/chemo/ipi compared with pembrolizumab monotherapy
in patients with advanced or metastatic, squamous or non-squamous NSCLC whose
tumors express PD L1 in >=50% of tumor cells and who have received no prior
systemic treatment for their advanced disease. This study will be open-label
because the differences in administration and known distinct toxicities of the
therapies do not lend themselves to blinding.
Because this is the first study to evaluate the combination of REGN2810 and
ipilimumab and the combination or platinum doublet chemotherapy and ipilimumab,
there will be an early review of data to ensure patient safety after the first
10 patients in the REGN2810/ipi and the first 10 patients in the
REGN2810/chemo/ipi treatment arm have completed 4 weeks of follow-up following
the first dose of REGN2810/ipi or REGN2810/chemo/ipi respectively. An
additional safety review will be performed by the Independent Data Monitoring
Committee (IDMC) after the first 10 patients in the REGN2810/ipi and
REGN2810/chemo/ipi regimen have received all 4 doses of ipilimumab and have
been followed for at least 6 weeks after the last dose. This analysis will
include all patients who have been exposed to the combination treatment.
The study population is limited to previous and current smokers as the benefit
of PD-1 blockade has not been shown to the same extent in non-smokers likely
due to the lower mutational burden in this population
Old Saw Mill River Road 777
Tarrytown, NY 10591
US
Old Saw Mill River Road 777
Tarrytown, NY 10591
US
Listed location countries
Age
Inclusion criteria
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.
Exclusion criteria
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.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2017-001041-27-NL |
| CCMO | NL64676.056.18 |