Clinical trial NCT03409614: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non-small Cell Lung Cancer
Keywords: Stage IIIB
Stage IIIC
Stage IV
Non-squamous NSCLC
Squamous NSCLC
Lead sponsor: Regeneron Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2018-01-24
Enrollment: 790
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Overall survival
timeFrame: Up to 32 months
Secondary outcomes:
measure: Progression-free survival
timeFrame: Up to 32 months
measure: Objective response rate
timeFrame: Up to 32 months
measure: Duration of Response (DOR)
timeFrame: Up to 32 months
measure: Best overall response (BOR)
timeFrame: Up to 32 months
measure: Incidence of Treatment-emergent adverse events (TEAEs)
timeFrame: Up to 32 months
measure: Incidence of Dose-limiting toxicities (DLTs)
timeFrame: Up to 32 months
measure: Incidence of serious adverse events (SAEs)
timeFrame: Up to 32 months
measure: Incidence of deaths
timeFrame: Up to 32 months
measure: Incidence of laboratory abnormalities
timeFrame: Up to 32 months
measure: Overall survival rate
timeFrame: 12 months
measure: Overall survival rate
timeFrame: 18 months
measure: Overall survival rate
timeFrame: 24 months
measure: Quality of life as measured by EORTC QLQ-C30
timeFrame: Up to 32 months
measure: Quality of life as measured by EORTC QLQ-LC13
timeFrame: Up to 32 months
Other outcomes:
Locations:
city: Rancho Mirage
country: United States
facility: Regeneron Research Site
state: California
city: Riverside
country: United States
facility: Regeneron Research Site
state: California
city: Whittier
country: United States
facility: Regeneron Research Site
state: California
city: Orange City
country: United States
facility: Regeneron Research Site
state: Florida
city: Saint Petersburg
country: United States
facility: Regeneron Research Site
state: Florida
city: Wichita
country: United States
facility: Regeneron Research Site
state: Kansas
city: Bethesda
country: United States
facility: Regeneron Research Site
state: Maryland
city: Farmington
country: United States
facility: Regeneron Research Site
state: New Mexico
city: Gettysburg
country: United States
facility: Regeneron Research Site
state: Pennsylvania
city: Wien
country: Austria
facility: Regeneron Research Site
city: Baoding
country: China
facility: Regeneron Research Site
city: Beijing
country: China
facility: Regeneron research Site
city: Changsha
country: China
facility: Regeneron Research Site
city: Guangzhou
country: China
facility: Regeneron Research Site
city: Hangzhou Shi
country: China
facility: Regeneron Research Site
city: Hangzhou
country: China
facility: Regeneron Research Site
city: Hangzhou
country: China
facility: Regeneron Research Site
city: Hangzhou
country: China
facility: Regeneron Research Site
city: Jinan
country: China
facility: Regeneron Research Site
city: Linyi City
country: China
facility: Regeneron Research Site
city: Nanjing Shi
country: China
facility: Regeneron Research Site
city: Shanghai
country: China
facility: Regeneron Research Site
city: Shanghai
country: China
facility: Regeneron Research Site
city: Shenyang
country: China
facility: Regeneron Research Site
city: Xiangyang Shi
country: China
facility: Regeneron Research Site
city: Zhengzhou City
country: China
facility: Regeneron Research Site
city: Zhengzhou
country: China
facility: Regeneron Research Site
city: Bayonne
country: France
facility: Regeneron Research Site
city: Creteil
country: France
facility: Regeneron Research Site
city: Le Mans
country: France
facility: Regeneron Research Site
city: Lille
country: France
facility: Regeneron Research Site
city: Lyon
country: France
facility: Regeneron Research Site
city: Mont-de-Marsan
country: France
facility: Regeneron Research Site
city: Saint Herblain Cedex
country: France
facility: Regeneron Research Site
city: Saint-Mandé
country: France
facility: Regeneron Research Site
city: Strasbourg
country: France
facility: Regeneron Research Site
city: Batumi
country: Georgia
facility: Regeneron Research Site
city: Tbilisi
country: Georgia
facility: Regeneron Research Site
city: Tbilisi
country: Georgia
facility: Regeneron Research Site
city: Tbilisi
country: Georgia
facility: Regeneron Research Site #1
city: Tbilisi
country: Georgia
facility: Regeneron Research Site #2
city: Tbilisi
country: Georgia
facility: Regeneron Research Site
city: Thessaloniki
country: Greece
facility: Regeneron Research Site
state: Macedonia
city: Athens
country: Greece
facility: Regeneron Research Site
city: Kifisia
country: Greece
facility: Regeneron Research Site
city: Larissa
country: Greece
facility: Regeneron Research Site
city: Pylaia
country: Greece
facility: Regeneron Research Site
city: Thessaloniki
country: Greece
facility: Regeneron Research Site
city: Dublin
country: Ireland
facility: Regeneron Research Site
city: Limerick
country: Ireland
facility: Regeneron Research Site
city: Cremona
country: Italy
facility: Regeneron Research Site
city: Meldola
country: Italy
facility: Regeneron Research Site
city: Milano
country: Italy
facility: Regeneron Research Site
city: Monserrato
country: Italy
facility: Regeneron Research Site
city: Piacenza
country: Italy
facility: Regeneron Research Site
city: Saronno
country: Italy
facility: Regeneron Research Site
city: Terni
country: Italy
facility: Regeneron Research Site
city: Treviglio
country: Italy
facility: Regeneron Research Site
city: Cheongju-si
country: Korea, Republic of
facility: Regeneron Research Site
city: Incheon
country: Korea, Republic of
facility: Regeneron Research Site
city: Jeonju
country: Korea, Republic of
facility: Regeneron Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Regeneron Research Site
city: Seongnam-si
country: Korea, Republic of
facility: Regeneron Research Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Research Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Research Site
city: Seoul
country: Korea, Republic of
facility: Regeneron Research Site
city: Suwon-si
country: Korea, Republic of
facility: Regeneron Research Site
city: Klaipeda
country: Lithuania
facility: Regeneron Research Site
city: Vilnius
country: Lithuania
facility: Regeneron Research Site
city: Kuala Lumpur
country: Malaysia
facility: Regeneron Research Site
state: Wilayah Persekutuan
city: Johor Bahru
country: Malaysia
facility: Regeneron Research Site
city: Kota Kinabalu
country: Malaysia
facility: Regeneron Research Site
city: Kuala Lumpur
country: Malaysia
facility: Regeneron Research Site
city: Kuala Lumpur
country: Malaysia
facility: Regeneron Research Site
city: Kuantan
country: Malaysia
facility: Regeneron Research Site
city: Penang
country: Malaysia
facility: Regeneron Research Site
city: Pulau Pinang
country: Malaysia
facility: Regeneron Research Site
city: Tanjung Bungah
country: Malaysia
facility: Regeneron Research Site
city: Gdynia
country: Poland
facility: Regeneron Research Site
state: Pomorskie
city: Lublin
country: Poland
facility: Regeneron Research Site
city: Olsztyn
country: Poland
facility: Regeneron Research Site
city: Otwock
country: Poland
facility: Regeneron Research Site
city: Poznan
country: Poland
facility: Regeneron Research Site
city: Rzeszow
country: Poland
facility: Regeneron Research Site
city: Torun
country: Poland
facility: Regeneron Research Site
city: Wodzisław Śląski
country: Poland
facility: Regeneron Research Site
city: Łódź
country: Poland
facility: Regeneron Research Site
city: Cluj Napoca
country: Romania
facility: Regeneron Research Site
city: Cluj Napoca
country: Romania
facility: Regeneron Research Site
city: Craiova
country: Romania
facility: Regeneron Research Site
city: Craiova
country: Romania
facility: Regeneron Research Site
city: Craiova
country: Romania
facility: Regeneron Research Site
city: Ufa
country: Russian Federation
facility: Regeneron Research Site
state: Republic Bashkortost
city: Arkhangel'sk
country: Russian Federation
facility: Regeneron Research Site
city: Belgorod
country: Russian Federation
facility: Regeneron Research Site
city: Chelyabinsk
country: Russian Federation
facility: Regeneron Research Site
city: Ekaterinburg
country: Russian Federation
facility: Regeneron Research Site
city: Kaluga
country: Russian Federation
facility: Regeneron Research Site
city: Kazan
country: Russian Federation
facility: Regeneron Research Site
city: Kursk
country: Russian Federation
facility: Regeneron Research Site
city: Moscow region
country: Russian Federation
facility: Regeneron Research Site
city: Moscow
country: Russian Federation
facility: Regeneron Research Site
city: Moscow
country: Russian Federation
facility: Regeneron Research Site
city: Omsk
country: Russian Federation
facility: Regeneron Research Site
city: Pushkin
country: Russian Federation
facility: Regeneron Research Site
city: Pyatigorsk
country: Russian Federation
facility: Regeneron Research Site
city: Saint Petersburg
country: Russian Federation
facility: Regeneron Research Site
city: Saint Petersburg
country: Russian Federation
facility: Regeneron Research Site
city: Saint Petersburg
country: Russian Federation
facility: Regeneron Research Site
city: Samara
country: Russian Federation
facility: Regeneron Research Site
city: Saransk
country: Russian Federation
facility: Regeneron Research Site
city: Sochi
country: Russian Federation
facility: Regeneron Research Site
city: Tomsk
country: Russian Federation
facility: Regeneron Research Site
city: Tomsk
country: Russian Federation
facility: Regeneron Research Site
city: Banka
country: Slovakia
facility: Regeneron Research Site
city: Ratchathewi
country: Thailand
facility: Regeneron Research Site #2
state: Bangkok
city: Muang
country: Thailand
facility: Regeneron Research Site
state: Chiang Rai
city: A. Mueang
country: Thailand
facility: Regeneron Research Site
state: Lampang
city: Muang
country: Thailand
facility: Regeneron Research Site
state: Phitsanulok
city: Hat Yai
country: Thailand
facility: Regeneron Research Site
state: Songkhla
city: Muang
country: Thailand
facility: Regeneron Research Site
city: Ratchathewi
country: Thailand
facility: Regeneron Research Site #1
city: Udonthani
country: Thailand
facility: Regeneron Research Site
city: Adana
country: Turkey
facility: Regeneron Research Site
city: Ankara
country: Turkey
facility: Regeneron Research Site
city: Istanbul
country: Turkey
facility: Regeneron Research Site
city: Istanbul
country: Turkey
facility: Regeneron Research Site
city: Dnipro
country: Ukraine
facility: Regeneron Research Site
city: Kharkiv
country: Ukraine
facility: Regeneron Research Site
city: Kiev
country: Ukraine
facility: Regeneron Research Site
city: Kirovohrad
country: Ukraine
facility: Regeneron Research Site
city: Uzhgorod
country: Ukraine
facility: Regeneron Research Site
city: Vinnytsia
country: Ukraine
facility: Regeneron Research Site
Study officials:
affiliation: Regeneron Pharmaceuticals
name: Clinical Trial Management
role: STUDY_DIRECTOR
References: