Combinations of Cemiplimab (Anti-PD-1 Antibody) and Platinum-based Doublet Chemotherapy in Patients With Lung Cancer

• ClinicalTrials.gov Identifier: NCT03409614
• Recruitment Status: Active, not recruiting
• First Posted: January 24, 2018
• Last Update Posted: April 25, 2024
• Sponsor: Regeneron Pharmaceuticals
• Collaborator: Sanofi
• Information provided by (Responsible Party): Regeneron Pharmaceuticals

Tracking Information

• First Submitted Date: January 10, 2018
• First Posted Date: January 24, 2018
• Last Update Posted Date: April 25, 2024
• Actual Study Start Date: March 6, 2018
• Estimated Primary Completion Date: February 3, 2025 (Final data collection date for primary outcome measure)
• Current Primary Outcome Measures (submitted: June 29, 2020): Overall survival [ Time Frame: Up to 32 months ]
• Original Primary Outcome Measures (submitted: January 23, 2018): PFS as assessed by a blinded Independent Review Committee (IRC) based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) assessments [ Time Frame: Up to 32 months ]

Current Secondary Outcome Measures (submitted: June 29, 2020)

• Progression-free survival [ Time Frame: Up to 32 months ]
• Objective response rate [ Time Frame: Up to 32 months ]
• Duration of Response (DOR) [ Time Frame: Up to 32 months ]
• Best overall response (BOR) [ Time Frame: Up to 32 months ]
• Incidence of Treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 32 months ]
• Incidence of Dose-limiting toxicities (DLTs) [ Time Frame: Up to 32 months ]
  Part 1 only
• Incidence of serious adverse events (SAEs) [ Time Frame: Up to 32 months ]
• Incidence of deaths [ Time Frame: Up to 32 months ]
• Incidence of laboratory abnormalities [ Time Frame: Up to 32 months ]
• Overall survival rate [ Time Frame: 12 months ]
• Overall survival rate [ Time Frame: 18 months ]
• Overall survival rate [ Time Frame: 24 months ]
• Quality of life as measured by EORTC QLQ-C30 [ Time Frame: Up to 32 months ]
  European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
• Quality of life as measured by EORTC QLQ-LC13 [ Time Frame: Up to 32 months ]
  Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)

Original Secondary Outcome Measures (submitted: January 23, 2018)

• Overall survival (OS) [ Time Frame: Up to 32 months ]
• Objective response rate (ORR) [ Time Frame: Up to 32 months ]
• Incidence of Treatment-emergent adverse events (TEAEs) [ Time Frame: Up to 32 months ]
• Incidence of Dose-limiting toxicities (DLTs) [ Time Frame: Up to 32 months ]
• Incidence of serious adverse events (SAEs) [ Time Frame: Up to 32 months ]
• Incidence of deaths [ Time Frame: Up to 32 months ]
• Incidence of laboratory abnormalities [ Time Frame: Up to 32 months ]
• Overall survival [ Time Frame: 12 months ]
• Overall survival [ Time Frame: 18 months ]
• Quality of life [ Time Frame: Up to 32 months ]
  As measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30)
• Quality of life [ Time Frame: Up to 32 months ]
  As measured by the Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13)

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

Descriptive Information

• Brief Title: Combinations of Cemiplimab (Anti-PD-1 Antibody) and Platinum-based Doublet Chemotherapy in Patients With Lung Cancer
• Official Title: A Two-Part Randomized, Phase 3 Study of Combinations of Cemiplimab (Anti-PD-1 Antibody) and Platinum-based Doublet Chemotherapy in First-line Treatment of Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

Brief Summary

The primary objectives of this study are:

Part 1: To compare the overall survival (OS) of cemiplimab/chemo-f and cemiplimab/chemo-l/ipi versus platinum-based doublet chemotherapy in the first-line treatment of patients with advanced squamous or nonsquamous non-small cell lung cancer (NSCLC) with tumors expressing PD-L1 in <50% of tumor cells.

Part 2: To compare the OS of cemiplimab/chemo-f with placebo/chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC irrespective of PD-L1 expression.

The key secondary objectives are:

Part 1: To compare the progression-free survival (PFS) and objective response rate (ORR) of cemiplimab/chemo-f and cemiplimab/chemo-l/ipi versus chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC and tumors expressing PD-L1 in <50% of tumor cells.

Part 2: To compare the PFS and ORR of cemiplimab/chemo-f versus placebo/chemo-f in the first-line treatment of patients with advanced squamous or non-squamous NSCLC irrespective of PD-L1 expression.

• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3

Study Design

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:

Part 1: Open label Part 2: Double blind

Primary Purpose: Treatment

• Condition: Non-small Cell Lung Cancer

Intervention

• Drug: REGN2810
  REGN2810 plus Platinum-based doublet chemotherapy Part 1 and Part 2
  Other Name: cemiplimab
• Drug: REGN2810/chemo/ipi
  REGN2810 plus abbreviated chemotherapy plus Ipilimumab Part 1
  Other Name: cemiplimab
• Other: Chemotherapy
  Platinum-based doublet chemotherapy Part 1
• Drug: Placebo
  Matching placebo Part 2

Study Arms

• Chemo
  Part 1: Chemotherapy
  Interventions:

  • Other: Chemotherapy
  • Drug: Placebo
• Experimental: REGN2810+Chemo Part 1
  Part 1: REGN2810+chemo
  Intervention: Drug: REGN2810
• Experimental: REGN2810+AbbrevChemo+ipi
  Part 1: REGN2810+abbrev chemo+ipi
  Intervention: Drug: REGN2810/chemo/ipi
• Experimental: Placebo+Chemo
  Part 2: Placebo plus chemo
  Intervention: Drug: Placebo
• Experimental: REGN2810+Chemo Part 2
  Part 2: REGN2810+chemo
  Intervention: Drug: REGN2810

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: October 7, 2020): 790
• Original Estimated Enrollment (submitted: January 23, 2018): 690
• Estimated Study Completion Date: February 3, 2025
• Estimated Primary Completion Date: February 3, 2025 (Final data collection date for primary outcome measure)

Eligibility Criteria

Key Inclusion Criteria:

1. Men and women ≥20 years of age for Japanese patients
2. Patients with histologically or cytologically documented squamous or non-squamous NSCLC with stage IIIB or IIIC 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 (≤5 months) or on-study obtained formalin-fixed, paraffin-embedded tumor tissue sample from a metastatic or recurrent site, which has not previously been irradiated
4. Part 1 only: Expression of PD-L1 in <50% of tumor cells determined by a commercially available assay performed by the central laboratory
5. At least 1 radiographically measurable 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. Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
7. Anticipated life expectancy of at least 3 months

Key Exclusion Criteria:

1. Part 1 only: Patients who 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 Epidermal growth factor receptor (EGFR) gene mutations, Anaplastic lymphoma kinase (ALK) gene translocations, or C-ros oncogene receptor tyrosine kinase(ROS1) fusions
4. Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment
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
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)
7. Patients with a condition requiring corticosteroid therapy (>10 mg prednisone/day or equivalent) within 14 days of randomization

Note: Other protocol defined Inclusion/Exclusion criteria may 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: Austria, China, France, Georgia, Greece, Ireland, Italy, Korea, Republic of, Lithuania, Malaysia, Poland, Romania, Russian Federation, Slovakia, Thailand, Turkey, Ukraine, United States
• Removed Location Countries: Czechia, Netherlands

Administrative Information

• NCT Number: NCT03409614
• Other Study ID Numbers: R2810-ONC-16113; 2017-001311-36 ( 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: April 2024