A STUDY OF REGN2810 (ANTI-PD 1 ANTIBODY) VERSUS STANDARD OF CARE IN PATIENTS WITH LUNG CANCER

Phase 1

Conditions: on-Small Cell Lung Cancer
Therapeutic area: Diseases [C] - Cancer [C04]

Registration Number: EUCTR2016-004407-31-PT

Lead Sponsor: Regeneron Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Authorised-recruitment may be ongoing or finished

Sex: All

Target Recruitment: 300

Inclusion Criteria

1.Men and women =18 years of age (=20 years of age in Japan)
2.Patients with histologically or cytologically documented squamous or non squamous NSCLC with stage IIIB or stage IV disease who received no prior systemic treatment for recurrent or metastatic NSCLC
a.Patients who received adjuvant or neoadjuvant platinum-doublet chemotherapy (after surgery and/or radiation therapy) and developed recurrent or metastatic disease more than 6 months after completing therapy are eligible
3.Archival or newly obtained formalin-fixed tumor tissue from a metastatic/recurrent site, which has not previously been irradiated
4.Tumor cells expressing PD L1 in =50% of tumor cells by IHC performed by the central laboratory
5.At least 1 radiographically measureable lesion by computed tomography (CT) or magnetic resonance imaging (MRI) per RECIST 1.1 criteria (see Appendix 4). 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
8.Adequate organ and bone marrow function as defined below:
a.Hemoglobin =9.0 g/dL
b.Absolute neutrophil count =1.5 × 109/L
c.Platelet count =100,000/mm3
d.Glomerular filtration rate (GFR) >30 mL/min/1.73m2
e.Total bilirubin =1.5 × upper limit of normal (ULN) (if liver metastases =3 × ULN), with the exception of patients diagnosed with clinically confirmed Gilbert’s syndrome
f.Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =3 × ULN or =5 × ULN, if liver metastases
g.Alkaline phosphatase =2.5 × ULN (or =5.0 × ULN, if liver or bone metastases)
h.Not meeting criteria for Hy’s law (ALT >3 × ULN and bilirubin >2 × ULN)
9.Willing and able to comply with clinic visits and study-related procedures
10.Provide signed informed consent
11.Able to understand and complete study-related questionnaires

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 210
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 90

Exclusion Criteria

1.Patients that 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.
3.Patients with tumors tested positive for EGFR gene mutations, ALK gene translocations, or 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, organizing pneumonia) or active, noninfectious pneumonitis that required immune-suppressive doses of glucocorticoids to assist with management. A history of radiation pneumonitis in the radiation field is permitted.
6.Patients with active, known, or suspected autoimmune disease that has required systemic therapy in the past 2 years. Patients with vitiligo, type I diabetes mellitus, and hypothyroidism (including hypothyroidism due to autoimmune thyroiditis) only requiring hormone replacement are permitted to enroll.
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.
8.Another malignancy that is progressing or requires treatment, with the exception of nonmelanomatous skin cancer that has undergone potentially curative therapy, or in situ cervical carcinoma or any other tumor that has been treated, and the patient is deemed to be in complete remission for at least 2 years prior to study entry, and no additional therapy is required during the study period.
9.Known active hepatitis B (positive result) or hepatitis C (known positive result) and known quantitative HCV RNA results greater than the lower limits of detection of the assay)
10.Known history of human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome indicating uncontrolled active infection. Patients on highly active antiretroviral therapy with undetectable RNA levels and CD4 counts above 350 are permitted.
11.Active infection requiring systemic therapy within 14 days prior to randomization
12.Prior therapy with anti-PD 1 or anti-PD L1. Prior exposure to other immunomodulatory or vaccine therapy such as anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) antibodies is permitted, but the last dose of such an antibody should have been at least 3 months prior to the first dose of study drug.
13.Treatment-related immune-mediated AEs from immune-modulatory agents (including but not limited to anti-PD1/PD-L1 Mabs, anti-CTLA4 monoclonal antibodies, and PI3K d inhibitors) that have not resolved to baseline at least 3 months prior to initiation of treatment with study therapy. Patients are excluded from treatment with REGN2810 if they experienced immune-mediated AEs related to prior treatment with a blocker of the PD-1/PD-L1 pathway that were grade 3 or 4 in severity and/or required discontinuation of the agent, regardless of time of occurrence.
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