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

• ClinicalTrials.gov Identifier: NCT03088540
• Recruitment Status: Active, not recruiting
• First Posted: March 23, 2017
• Last Update Posted: October 23, 2023
• Sponsor: Regeneron Pharmaceuticals
• Collaborator: Sanofi
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: March 3, 2017
• First Posted Date: March 23, 2017
• Last Update Posted Date: October 23, 2023
• Actual Study Start Date: May 29, 2017
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: October 31, 2019)

• 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.

Original Primary Outcome Measures (submitted: March 16, 2017)

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 30 months ]

PFS as assessed by a blinded IRC using RECIST 1.1.

Current Secondary Outcome Measures (submitted: October 31, 2019)

• Objective response rates (ORR) [ Time Frame: 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) [ Time Frame: 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
• Compare the duration of response (DOR) of cemiplimab versus platinum based chemotherapies [ 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 ]
  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
• 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) [ Time Frame: Baseline up to 26 months after treatment ]
• Change from baseline in in lung cancer symptom scores as measured by the EORTC Lung Cancer 13 (EORTC QLQ-LC13) [ Time Frame: Baseline up to 26 months after treatment ]
• Incidence of Adverse Events (AEs) [ Time Frame: Baseline up to 68 months after treatment ]
• Incidence of serious adverse events (SAEs) [ Time Frame: Baseline up to 68 months after treatment ]
• Incidence of deaths [ Time Frame: Baseline up to 68 months after treatment ]
• Incidence of laboratory abnormalities [ Time Frame: Baseline up to 68 months after treatment ]
  Number of patients with laboratory abnormalities
• Measure concentrations of cemiplimab in serum [ Time Frame: Baseline up to 68 months after treatment ]
  Maximum Plasma Concentration [Cmax]
• Characterize the pharmacokinetics (PK) of cemiplimab [ Time Frame: Baseline up to 68 months after treatment ]
  Area Under the Curve [AUC]

Original Secondary Outcome Measures (submitted: March 16, 2017)

• Overall survival (OS) [ Time Frame: From date of randomization until date of death, assessed up to 39 months ]
  Overall survival will be defined as the time from randomization to the date of death.
• Objective response rates (ORR) [ Time Frame: 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 30 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) [ 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 30 months ]
  The BOR, as determined by the IRC per RECIST 1.1
• Compare the duration of response (DOR) of REGN2810 versus platinum based chemotherapies [ 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 30 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
• Assess quality of life (QOL) of patients treated with REGN2810 versus patients receiving platinum-based chemotherapies as measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) [ Time Frame: Baseline up to 30 days after treatment ]
• Change From Baseline in Quality of Life as measured by the Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13) [ Time Frame: Baseline up to 30 days after treatment ]
• Incidence of Adverse Events (AEs) [ Time Frame: Baseline up to 12 months after treatment ]
• Incidence of serious adverse events (SAEs) [ Time Frame: Baseline up to 12 months after treatment ]
• Incidence of deaths [ Time Frame: Baseline up to 12 months after treatment ]
• Incidence of laboratory abnormalities [ Time Frame: Baseline up to 12 months after treatment ]
  Number of patients with laboratory abnormalities
• Measure concentrations of REGN2810 in serum [ Time Frame: Baseline up to 12 months after treatment ]
  Maximum Plasma Concentration [Cmax]
• Characterize the pharmacokinetics (PK) of REGN2810 [ Time Frame: Baseline up to 12 months after treatment ]
  Area Under the Curve [AUC]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

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

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 Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Crossover Assignment; Masking: None (Open Label); Primary Purpose: Treatment

Condition

• Carcinoma，Non-Small-Cell Lung
• Lung Carcinomas, Non-Small-Cell
• Non-small-cell Lung Carcinoma
• Nonsmall Cell Lung Cancer

Intervention

• Drug: Pemetrexed
  Patients will be administered pemetrexed chemotherapy as per protocol with either cisplatin or carboplatin
• Drug: Paclitaxel
  Patients will be administered paclitaxel chemotherapy as per protocol with either cisplatin or carboplatin
• Drug: Gemcitabine
  Patients will be administered gemcitabine chemotherapy as per protocol with either cisplatin or carboplatin
• Drug: Cisplatin
  Administered with either Pemetrexed, Paclitaxel or gemcitabine.
• Drug: Carboplatin
  Administered with either Pemetrexed, Paclitaxel or gemcitabine.
• Drug: cemiplimab
  Patients will be administered cemiplimab as per protocol.
  Other Names:

  • REGN2810
  • Libtayo

Study Arms

• Active Comparator: 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

  Interventions:

  • Drug: Pemetrexed
  • Drug: Paclitaxel
  • Drug: Gemcitabine
  • Drug: Cisplatin
  • Drug: Carboplatin
• Experimental: cemiplimab
  cemiplimab regimen as monotherapy as per study protocol
  Intervention: Drug: cemiplimab

Publications *

• Gumus M, Chen CI, Ivanescu C, Kilickap S, Bondarenko I, Ozguroglu M, Gogishvili M, Turk HM, Cicin I, Harnett J, Mastey V, Naumann U, Reaney M, Konidaris G, Sasane M, Brady KJS, Li S, Gullo G, Rietschel P, Sezer A. Patient-reported outcomes with cemiplimab monotherapy for first-line treatment of advanced non-small cell lung cancer with PD-L1 of >/=50%: The EMPOWER-Lung 1 study. Cancer. 2023 Jan 1;129(1):118-129. doi: 10.1002/cncr.34477. Epub 2022 Oct 29. Erratum In: Cancer. 2024 May 1;130(9):1715.
• Sezer A, Kilickap S, Gumus M, Bondarenko I, Ozguroglu M, Gogishvili M, Turk HM, Cicin I, Bentsion D, Gladkov O, Clingan P, Sriuranpong V, Rizvi N, Gao B, Li S, Lee S, McGuire K, Chen CI, Makharadze T, Paydas S, Nechaeva M, Seebach F, Weinreich DM, Yancopoulos GD, Gullo G, Lowy I, Rietschel P. Cemiplimab monotherapy for first-line treatment of advanced non-small-cell lung cancer with PD-L1 of at least 50%: a multicentre, open-label, global, phase 3, randomised, controlled trial. Lancet. 2021 Feb 13;397(10274):592-604. doi: 10.1016/S0140-6736(21)00228-2.

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: April 13, 2020): 712
• Original Estimated Enrollment (submitted: March 16, 2017): 300
• Estimated Study Completion Date: April 30, 2024
• Estimated Primary Completion Date: April 30, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Australia, Belarus, Brazil, Bulgaria, Chile, China, Colombia, Czechia, Georgia, Greece, Hungary, Jordan, Lebanon, Malaysia, Mexico, Philippines, Poland, Romania, Russian Federation, Spain, Taiwan, Thailand, Turkey, Ukraine

Administrative Information

• NCT Number: NCT03088540
• Other Study ID Numbers: R2810-ONC-1624; 2016-004407-31 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Regeneron Pharmaceuticals
• Original Responsible Party: Same as current
• Current Study Sponsor: Regeneron Pharmaceuticals
• Original Study Sponsor: Same as current
• Collaborators: Sanofi

Investigators

• Study Director: Clinical Trial Management; Regeneron Pharmaceuticals

• PRS Account: Regeneron Pharmaceuticals
• Verification Date: October 2023