Study of REGN 2810 Compared to Platinum-Based Chemotherapies in Participants With Metastatic Non-Small Cell Lung Cancer (NSCLC)

Phase 3

Completed

• Conditions: Lung Carcinomas, Non-Small-Cell; Non-small-cell Lung Carcinoma; Nonsmall Cell Lung Cancer; Carcinoma，Non-Small-Cell Lung
• Interventions: Drug: Pemetrexed; Drug: cemiplimab; Drug: Paclitaxel; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin

• Registration Number: NCT03088540
• Lead Sponsor: Regeneron Pharmaceuticals

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.

Study Timeline

• Study First Submitted: 2017-03-03
• Study First Submitted QC: 2017-03-16
• Study First Posted: 2017-03-23
• Study Start: 2017-05-29
• Status Verified: 2025-04
• Primary Completion: 2025-04-18
• Study Completion: 2025-04-18
• Last Update Submitted: 2025-04-30
• Last Update Posted: 2025-05-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 712

Inclusion Criteria

A patient must meet the following criteria to be eligible for inclusion in the study:

1. 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
2. Archival or newly obtained formalin-fixed tumor tissue from a metastatic/recurrent site, which has not previously been irradiated
3. Tumor cells expressing PD L1 above a specific percentage of tumor cells by IHC performed by the central laboratory
4. At least 1 radiographically measureable lesion per RECIST 1.1
5. ECOG performance status of ≤1
6. Anticipated life expectancy of at least 3 months
7. Adequate organ and bone marrow function

Key

Exclusion Criteria

A patient who meets any of the following criteria will be excluded from the study:

1. Patients that have never smoked, defined as smoking <100 cigarettes in a lifetime
2. Active or untreated brain metastases or spinal cord compression
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 randomization
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 as long as pneumonitis resolved ≥6 months prior to randomization
6. Patients with active, known, or suspected autoimmune disease that has required systemic therapy in the past 2 years
7. Patients with a condition requiring corticosteroid therapy (>10 mg prednisone/day or equivalent) within 14 days of randomization
8. Another malignancy that is progressing or requires treatment
9. Uncontrolled infection with hepatitis B or hepatitis C or human immunodeficiency virus (HIV) or diagnosis of immunodeficiency
10. Active infection requiring systemic therapy within 14 days prior to randomization
11. Prior therapy with anti-PD 1 or anti-PD L1
12. Treatment-related immune-mediated AEs from immune-modulatory agents
13. Receipt of an investigational drug or device within 30 days
14. Receipt of a live vaccine within 30 days of planned start of study medication
15. Major surgery or significant traumatic injury within 4 weeks prior to first dose
16. Documented allergic or acute hypersensitivity reaction attributed to antibody treatments
17. Known psychiatric or substance abuse disorder that would interfere with participation with the requirements of the study, including current use of any illicit drugs
18. Pregnant or breastfeeding women
19. Women of childbearing potential or men who are unwilling to practice highly effective contraception prior to the initial dose/start of the first treatment, during the study, and for at least 6 months after the last dose

Note: Other protocol defined Inclusion/Exclusion criteria apply.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Standard-of-care chemotherapy	Gemcitabine	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
Standard-of-care chemotherapy	Cisplatin	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
Standard-of-care chemotherapy	Pemetrexed	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
Standard-of-care chemotherapy	Paclitaxel	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
Standard-of-care chemotherapy	Carboplatin	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
cemiplimab	cemiplimab	cemiplimab regimen as monotherapy as per study protocol

Primary Outcome Measures

Name	Time	Method
Overall survival (OS)	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	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 Outcome Measures

Name	Time	Method
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	Area Under the Curve \[AUC\]
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	The number of patients with a best overall response (BOR) of confirmed Complete Response (CR) or Partial Response (PR) divided by the number of patients in the efficacy analysis set
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	The BOR, as determined by the IRC per RECIST 1.1
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	Duration of response will be defined as the time between the date of first response (CR or PR) to the date of the first documented tumor progression (per RECIST 1.1) or the date of subsequent anti-cancer therapy or death due to any cause, whichever comes first
Measure concentrations of cemiplimab in serum	Baseline up to 68 months after treatment	Maximum Plasma Concentration \[Cmax\]
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	Number of patients with laboratory abnormalities

Trial Locations

Locations (12)

Clinical Study Site 2; 🇺🇦 Kyiv, Ukraine

Clinical Study Site 3; 🇹🇷 İzmir, Turkey

Clinical Study Site #3; 🇧🇷 São Paulo, Brazil

Clinical Study Site; 🇺🇦 Úzhgorod, Ukraine

Clinical Study Site 1; 🇺🇦 Kyiv, Ukraine

Clincial Study Site; 🇨🇱 Viña Del Mar, Chile

Clinical Study Site #4; 🇧🇷 Sao Paulo, Brazil

Clinical Study Site #6; 🇬🇪 Tbilisi, Georgia

Clinical Study Site #2; 🇹🇭 Bangkok, Thailand

Clinical Study Site 4; 🇹🇷 Istanbul, Turkey

Clinical Study Site 5; 🇹🇷 Ankara, Turkey

Clinical Study Site #1; 🇹🇭 Bangkok, Thailand