A Global, Randomised, Phase 3, Open-label Study of REGN2810 (ANTI-PD 1 Antibody) Versus Platinum Based Chemotherapy in First Line Treatment of Patients With Advanced or Metastatic PD L1+Non-small Cell Lung Cancer
Overview
- Phase
- Phase 3
- Intervention
- Pemetrexed
- Conditions
- Carcinoma，Non-Small-Cell Lung
- Sponsor
- Regeneron Pharmaceuticals
- Enrollment
- 712
- Locations
- 192
- Primary Endpoint
- Overall survival (OS)
- Status
- Completed
- Last Updated
- 2 months ago
Overview
Brief Summary
The primary objectives of the study are:
- To compare the overall survival (OS) of cemiplimab versus standard-of-care platinum-based chemotherapies in the first-line treatment of patients with advanced or metastatic non-small cell lung cancer (NSCLC) whose tumors express PD-L1 in ≥50% of tumor cells
- To compare the progression-free survival (PFS) of cemiplimab versus standard-of-care platinum-based chemotherapies in the first-line treatment of patients with advanced or metastatic NSCLC whose tumors express PD-L1 in ≥50% of tumor cells
The key secondary objective of the study is to compare the objective response rate (ORR) of cemiplimab versus platinum-based chemotherapies
Detailed Description
There is option to join genomics sub-study.
Investigators
Eligibility Criteria
Inclusion Criteria
- •A patient must meet the following criteria to be eligible for inclusion in the study:
- •Patients with histologically or cytologically documented squamous or non squamous NSCLC with stage IIIB or stage IIIC disease who are not candidates for treatment with definitive concurrent chemoradiation or patients with stage IV disease who received no prior systemic treatment for recurrent or metastatic NSCLC
- •Archival or newly obtained formalin-fixed tumor tissue from a metastatic/recurrent site, which has not previously been irradiated
- •Tumor cells expressing PD L1 above a specific percentage of tumor cells by IHC performed by the central laboratory
- •At least 1 radiographically measureable lesion per RECIST 1.1
- •ECOG performance status of ≤1
- •Anticipated life expectancy of at least 3 months
- •Adequate organ and bone marrow function
Exclusion Criteria
- •A patient who meets any of the following criteria will be excluded from the study:
- •Patients that have never smoked, defined as smoking \<100 cigarettes in a lifetime
- •Active or untreated brain metastases or spinal cord compression
- •Patients with tumors tested positive for EGFR gene mutations, ALK gene translocations, or ROS1 fusions
- •Encephalitis, meningitis, or uncontrolled seizures in the year prior to randomization
- •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 as long as pneumonitis resolved ≥6 months prior to randomization
- •Patients with active, known, or suspected autoimmune disease that has required systemic therapy in the past 2 years
- •Patients with a condition requiring corticosteroid therapy (\>10 mg prednisone/day or equivalent) within 14 days of randomization
- •Another malignancy that is progressing or requires treatment
- •Uncontrolled infection with hepatitis B or hepatitis C or human immunodeficiency virus (HIV) or diagnosis of immunodeficiency
Arms & Interventions
Standard-of-care chemotherapy
Standard-of-care chemotherapy will administered from these options: Doses of Paclitaxel + cisplatin OR Doses Paclitaxel + carboplatin OR Doses Gemcitabine + cisplatin or Doses Gemcitabine + carboplatin OR Doses Pemetrexed + cisplatin followed by optional pemetrexed maintenance OR Doses Pemetrexed + carboplatin followed by optional pemetrexed maintenance
Intervention: Pemetrexed
Standard-of-care chemotherapy
Standard-of-care chemotherapy will administered from these options: Doses of Paclitaxel + cisplatin OR Doses Paclitaxel + carboplatin OR Doses Gemcitabine + cisplatin or Doses Gemcitabine + carboplatin OR Doses Pemetrexed + cisplatin followed by optional pemetrexed maintenance OR Doses Pemetrexed + carboplatin followed by optional pemetrexed maintenance
Intervention: Paclitaxel
Standard-of-care chemotherapy
Standard-of-care chemotherapy will administered from these options: Doses of Paclitaxel + cisplatin OR Doses Paclitaxel + carboplatin OR Doses Gemcitabine + cisplatin or Doses Gemcitabine + carboplatin OR Doses Pemetrexed + cisplatin followed by optional pemetrexed maintenance OR Doses Pemetrexed + carboplatin followed by optional pemetrexed maintenance
Intervention: Gemcitabine
Standard-of-care chemotherapy
Standard-of-care chemotherapy will administered from these options: Doses of Paclitaxel + cisplatin OR Doses Paclitaxel + carboplatin OR Doses Gemcitabine + cisplatin or Doses Gemcitabine + carboplatin OR Doses Pemetrexed + cisplatin followed by optional pemetrexed maintenance OR Doses Pemetrexed + carboplatin followed by optional pemetrexed maintenance
Intervention: Cisplatin
Standard-of-care chemotherapy
Standard-of-care chemotherapy will administered from these options: Doses of Paclitaxel + cisplatin OR Doses Paclitaxel + carboplatin OR Doses Gemcitabine + cisplatin or Doses Gemcitabine + carboplatin OR Doses Pemetrexed + cisplatin followed by optional pemetrexed maintenance OR Doses Pemetrexed + carboplatin followed by optional pemetrexed maintenance
Intervention: Carboplatin
cemiplimab
cemiplimab regimen as monotherapy as per study protocol
Intervention: cemiplimab
Outcomes
Primary Outcomes
Overall survival (OS)
Time Frame: From date of randomization until the date of death, assessed up to 68 months
Progression-free survival (PFS) as assessed by a blinded Independent review committee (IRC) using RECIST 1.1
Time Frame: From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 68 months
PFS as assessed by a blinded IRC using RECIST 1.1.
Secondary Outcomes
- Incidence of Adverse Events (AEs)(Baseline up to 68 months after treatment)
- Incidence of serious adverse events (SAEs)(Baseline up to 68 months after treatment)
- Incidence of deaths(Baseline up to 68 months after treatment)
- Characterize the pharmacokinetics (PK) of cemiplimab(Baseline up to 68 months after treatment)
- Objective response rates (ORR)(From date of randomization to the date of the first objectively documented progression or the date of subsequent anti-cancer therapy, whichever comes first, up to 68 months)
- Best overall response (BOR)(From date of randomization until the date of first documented progression or the date of subsequent anti-cancer therapy, whichever came first, assessed up to 68 months)
- Change from baseline in quality of life (QoL) scores as assessed by the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)(Baseline up to 26 months after treatment)
- Compare the duration of response (DOR) of cemiplimab versus platinum based chemotherapies(From date of randomization until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 68 months)
- Measure concentrations of cemiplimab in serum(Baseline up to 68 months after treatment)
- Change from baseline in in lung cancer symptom scores as measured by the EORTC Lung Cancer 13 (EORTC QLQ-LC13)(Baseline up to 26 months after treatment)
- Incidence of laboratory abnormalities(Baseline up to 68 months after treatment)