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

Regeneron Pharmaceuticals789 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

789

Conditions

Non-small Cell Lung Cancer

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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

Locations (133)

Regeneron Research Site

Rancho Mirage, California, United States

Regeneron Research Site

Riverside, California, United States

Regeneron Research Site

Whittier, California, United States

Regeneron Research Site

Orange City, Florida, United States

Regeneron Research Site

St. Petersburg, Florida, United States

Outcomes

Primary Outcomes

Part 1: Overall Survival (OS)

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

Time frame: Up to a maximum of 82.2 months

Part 2: OS

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

Time frame: Up to a maximum of 68.4 months

Secondary Outcomes

Part 1: Progression-free Survival (PFS) Per Independent Review Committee (IRC)

PFS as assessed by IRC per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST 1.1) was defined as the time from randomization to the date of the first documented tumor progression, or death due to any cause, whichever occurred earlier.

Time frame: Up to a maximum of 82.2 months

Part 2: PFS Per IRC

PFS as assessed by IRC per RECIST 1.1 was defined as the time from randomization to the date of the first documented tumor progression, or death due to any cause, whichever occurred earlier.

Time frame: Up to a maximum of 68.4 months

Part 1: Objective Response Rate (ORR) Per IRC

ORR as assessed by IRC per RECIST 1.1 was defined as the percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR).

Time frame: Up to 32 months

Part 2: ORR Per IRC

ORR as assessed by IRC per RECIST 1.1 was defined as the percentage of participants with a BOR of confirmed CR or PR.

Time frame: Up to 32 months

Part 1: Duration of Response (DoR)

DoR was defined as the time from date of first documented response of CR or PR to the date of first documented progressive disease (PD) or death due to any cause, whichever occurred earlier.

Time frame: Up to 32 months

Part 2: DoR

DoR was defined as the time from date of first documented response of CR or PR to the date of first documented PD or death due to any cause, whichever occurred earlier.

Time frame: Up to 32 months

Part 1: Best Overall Response (BOR) Per IRC

BOR was defined as the best overall response as determined by the IRC per RECIST 1.1, between the date of randomization and the date of first documented tumor progression or the date of subsequent anti-cancer therapy, whichever occurred earlier.

Time frame: Up to 32 months

Part 2: BOR Per IRC

Time frame: Up to 32 months

Part 1: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)

TEAEs were AEs that developed or worsened during the on-treatment period and any treatment-related AEs that occurred during the post-treatment period but prior to start of another anti-cancer systemic therapy.

Time frame: From first dose of study drug in Part 1, up to approximately 83 months

Part 2: Number of Participants With TEAEs

Time frame: From first dose of study drug in Part 2, up to approximately 69 months

Part 1: Number of Participants With Dose-limiting Toxicities (DLTs)

Part 1 only

Time frame: 28 days

Part 1: Number of Participants With Serious TEAEs

Serious TEAEs were defined as medically significant but not immediately life-threatening AEs that developed or worsened during the on-treatment period and any treatment-related AEs that occurred during the post-treatment period but prior to start of another anti-cancer systemic therapy.

Time frame: From first dose of study drug in Part 1, up to approximately 83 months

Part 2: Number of Participants With Serious TEAEs

Time frame: From first dose of study drug in Part 2, up to approximately 69 months

Part 1: Number of Deaths During the On-Treatment Period

The on-treatment period was defined as the day from the first dose of study drug to the day of the last dose of study drug plus 90 days or 1 day before participants receive their first dose of new anti-cancer systemic therapy, whichever is earlier.

Time frame: Up to 28 months

Part 2: Number of Deaths During the On-Treatment Period

Time frame: Up to 28 months

Part 1: Estimated Survival Probability

OS rate at a landmark (12, 18, and 24 months) was defined as the Kaplan-Meier (K-M) estimated probability of participants who survived due to any cause at the landmark after randomization.

Time frame: 12 months, 18 months, 24 months

Part 2: Estimated Survival Probability

OS rate at a landmark (12, 18, and 24 months) was defined as the K-M estimated probability of participants who survived due to any cause at the landmark after randomization.

Time frame: 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)

The EORTC QLQ-C30 is a 30-item questionnaire used to assess the overall quality of life (QoL) in cancer participants. It consists of 15 domains: 1 Global Health Status (GHS)/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Reported here are the EORTC QLQ-C30 GHS/QoL scores only. GHS/QoL is derived from two items-"How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?"-each scored from 1 (very poor) to 7 (excellent). The average of these two items is linearly transformed to a 0-100 scale; higher scores indicate better overall quality of life, and a positive change from baseline reflects improvement.

Time frame: 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

The EORTC QLQ-C30 is a 30-item questionnaire used to assess the overall QoL in cancer participants. It consists of 15 domains: 1 Global Health Status (GHS)/QoL scale, 5 functional scales (Physical, role, cognitive, emotional, social), 9 symptom scales/items (Fatigue, nausea and vomiting, pain, dyspnea, sleep disturbance, appetite loss, constipation, diarrhea, financial impact). Reported here are the EORTC QLQ-C30 GHS/QoL scores only. GHS/QoL is derived from two items-"How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?"-each scored from 1 (very poor) to 7 (excellent). The average of these two items is linearly transformed to a 0-100 scale; higher scores indicate better overall quality of life, and a positive change from baseline reflects improvement.

Time frame: 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)