Clinical Trials/NCT03409614

NCT03409614

Completed

Phase 3

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

Regeneron Pharmaceuticals136 sites in 8 countries789 target enrollmentMarch 6, 2018

ConditionsNon-small Cell Lung Cancer

InterventionsPlacebo Chemotherapy REGN2810 REGN2810/chemo/ipi

DrugsREGN2810 REGN2810/chemo/ipi Placebo

Overview

Phase: Phase 3
Intervention: Placebo
Conditions: Non-small Cell Lung Cancer
Sponsor: Regeneron Pharmaceuticals
Enrollment: 789
Locations: 136
Primary Endpoint: Overall survival
Status: Completed
Last Updated: 3 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Registry

clinicaltrials.gov

Start Date

March 6, 2018

End Date

February 27, 2025

Last Updated

3 days ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Regeneron Pharmaceuticals

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•Men and women ≥20 years of age for Japanese patients
•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
•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
•Part 1 only: Expression of PD-L1 in \<50% of tumor cells determined by a commercially available assay performed by the central laboratory
•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
•Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
•Anticipated life expectancy of at least 3 months

Exclusion Criteria

•Part 1 only: Patients who 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 Epidermal growth factor receptor (EGFR) gene mutations, Anaplastic lymphoma kinase (ALK) gene translocations, or C-ros oncogene receptor tyrosine kinase(ROS1) fusions
•Encephalitis, meningitis, or uncontrolled seizures in the year prior to enrollment
•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
•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)
•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

Arms & Interventions

Placebo+Chemo

Part 2: Placebo plus chemo

Intervention: Placebo

Chemo

Part 1: Chemotherapy

Intervention: Chemotherapy

REGN2810+Chemo Part 1

Part 1: REGN2810+chemo

Intervention: REGN2810

REGN2810+AbbrevChemo+ipi

Part 1: REGN2810+abbrev chemo+ipi

Intervention: REGN2810/chemo/ipi

REGN2810+Chemo Part 2

Part 2: REGN2810+chemo

Intervention: REGN2810

Chemo

Part 1: Chemotherapy

Intervention: Placebo

Outcomes

Primary Outcomes

Overall survival

Time Frame: Up to 32 months

Part 1: Overall Survival (OS)

Time Frame: Up to a maximum of 82.2 months

OS was defined as the time from randomization to the date of death due to any cause.

Part 2: OS

Time Frame: Up to a maximum of 68.4 months

OS was defined as the time from randomization to the date of death due to any cause.

Secondary Outcomes

Progression-free survival(Up to 32 months)
Duration of Response (DOR)(Up to 32 months)
Incidence of Treatment-emergent adverse events (TEAEs)(Up to 32 months)
Incidence of serious adverse events (SAEs)(Up to 32 months)
Overall survival rate(24 months)
Best overall response (BOR)(Up to 32 months)
Objective response rate(Up to 32 months)
Incidence of Dose-limiting toxicities (DLTs)(Up to 32 months)
Incidence of laboratory abnormalities(Up to 32 months)
Incidence of deaths(Up to 32 months)
Quality of life as measured by EORTC QLQ-LC13(Up to 32 months)
Quality of life as measured by EORTC QLQ-C30(Up to 32 months)
Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)(28 days)
Part 1: Progression-free Survival (PFS) Per Independent Review Committee (IRC)(Up to a maximum of 82.2 months)
Part 2: PFS Per IRC(Up to a maximum of 68.4 months)
Part 1: Objective Response Rate (ORR) Per IRC(Up to 32 months)
Part 2: ORR Per IRC(Up to 32 months)
Part 1: Duration of Response (DoR)(Up to 32 months)
Part 2: DoR(Up to 32 months)
Part 1: Best Overall Response (BOR) Per IRC(Up to 32 months)
Part 2: BOR Per IRC(Up to 32 months)
Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)(From first dose of study drug in Part 1, up to approximately 83 months)
Part 2: Number of Participants With TEAEs(From first dose of study drug in Part 2, up to approximately 69 months)
Part 1: Number of Participants With Serious TEAEs(From first dose of study drug in Part 1, up to approximately 83 months)
Part 2: Number of Participants With Serious TEAEs(From first dose of study drug in Part 2, up to approximately 69 months)
Part 1: Number of Deaths During the On-Treatment Period(Up to 28 months)
Part 2: Number of Deaths During the On-Treatment Period(Up to 28 months)
Part 1: Estimated Survival Probability(12 months, 18 months, 24 months)
Part 2: Estimated Survival Probability(12 months, 18 months, 24 months)
Part 1: Change From Baseline in Global Health Status Score as Measured by the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)(Baseline, Day 1 of 21-Day Cycles 2, 3, 4, 5, 6, 9, 12, 15, 18, 19, 20, 21, 22, 23, 24, 27, 30, 33, 36, 39, 40, 42, 45, 48, 51, 54, 57, 60, 63, 66; Follow-up visit 1 (14 to 30 days after last study treatment) then continued follow-up every 3 months)
Part 2: Change From Baseline in Global Health Status Score as Measured by the EORTC QLQ-C30(Baseline, Day 1 of 21-Day Cycles 2, 3, 4, 5, 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36; Follow-up 1 (14 to 30 days after last study treatment))