Clinical trial NCT03717155: Study of Avelumab and Cetuximab Plus Gemcitabine and Cisplatin in Participants With NSCLC
Official title: A Phase IIa, Single-arm, Multicenter Study to Investigate the Clinical Activity and Safety of Avelumab in Combination With Cetuximab Plus Gemcitabine and Cisplatin in Participants With Advanced Squamous NSCLC
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Squamous Non-Small Cell Lung Cancer
Keywords: Avelumab
Cetuximab
Cisplatin
Gemcitabine
Non-Small Cell Lung Cancer
Lead sponsor: Merck KGaA, Darmstadt, Germany
Sponsor class: INDUSTRY
First posted: 2018-10-24
Enrollment: 43
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: The main purpose of the study was to investigate the clinical activity and safety of avelumab in combination with cetuximab plus gemcitabine and cisplatin in participants with treatment-naïve advanced squamous non-small-cell lung cancer (NSCLC).


Eligibility criteria: Inclusion Criteria:

* Histologically-confirmed Stage IV metastatic or recurrent (Stage IV) NSCLC of squamous histology
* Availability of formalin-fixed paraffin-embedded (FFPE) block containing tumor tissue or a minimum of 15 (preferably 25) unstained tumor slides (cut within 1 week) suitable for Programmed death ligand 1 (PD-L1) expression and epidermal growth factor receptor (EGFR) expression/amplification assessments
* At least 1 measurable lesion per response evaluation criteria in solid tumors (RECIST) v1.1 criteria
* Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 to 1 at study entry
* Adequate hematological, hepatic and renal function
* Estimated life expectancy of at least 3 months
* Can give signed informed consent
* Other protocol defined inclusion criteria could apply

Exclusion Criteria:

* Participants whose tumor disease harbors an activating EGFR mutation or ALK rearrangement. Participants with tumors of unknown EGFR or ALK status will require testing only in never smokers
* All participants with brain metastases with protocol defined exceptions
* Previous malignant disease (other than NSCLC) within the last 5 years (except adequately treated non-melanoma skin cancers, carcinoma in situ of skin, bladder, cervix, colon/rectum, breast, or prostate) unless a complete remission without further recurrence was achieved at least 2 years prior to study entry and the participant was deemed to have been cured with no additional therapy required or anticipated to be required
* Active infection requiring systemic therapy
* Known history of human immunodeficiency virus or known acquired immunodeficiency syndrome
* Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection at screening (positive HBV surface antigen or HCV ribonucleic acid (RNA) if anti-HCV antibody screening test positive)
* Active autoimmune disease that might deteriorate when receiving an immunostimulatory agent
* Interstitial parenchymal lung disease
* Pregnancy or lactation
* Known alcohol or drug abuse as determined by the Investigator
* History of uncontrolled intercurrent illness
* Clinically significant (that is active) cardiovascular disease
* Known history of inflammatory colitis, inflammatory bowel disease, pneumonitis, pulmonary fibrosis
* Any psychiatric condition that would prohibit the understanding or rendering of informed consent or that would limit compliance with study requirements
* Prior/Concomitant Therapy as described in protocol
* Use of any investigational drug within 28 days before the start of study treatment
* Other protocol defined exclusion criteria could apply

Primary outcomes:
measure: Percentage of Participants With Confirmed Best Objective Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Assessed by Investigator
timeFrame: Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 612 days)
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (TEAEs), Treatment-Related Adverse Events (AEs), Treatment-Related Grade >=3 TEAEs and Immune-related Treatment Emergent AEs (irTEAEs)
timeFrame: Time from the first dose of study drug assessed up to (941 days)
measure: Progression-Free Survival (PFS) Time Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1
timeFrame: Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 737 days)
measure: Duration of Response (DOR)
timeFrame: Time from the first dose of study drug until occurrence of PD, death due to any cause or last tumor assessment (assessed up to 612 days)
measure: Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab
timeFrame: Pre-dose, 2 hours after end of infusion on Day 1, 8, 22 and 29; Pre-dose, 30 minutes after the end of infusion on Day 43, 50, 64, 71; Pre-dose, 3 hours after end of infusion on Day 85, 99, 113, 127, 169, 253, and 337
measure: Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab
timeFrame: Pre-dose, 2 hours after end of infusion on Day 1, 8, 22 and 29; Pre-dose, 30 minutes after the end of infusion on Day 43, 50, 64, 71; Pre-dose, 3 hours after end of infusion on Day 85, 99, 113, 127, 169, 253, and 337
measure: Serum Trough Concentration Levels (Ctrough) of Avelumab
timeFrame: Pre-dose: Day 8, Day 22, Day 29, Day 43, Day 50, Day 64, Day 71, Day 85, Day 99, Day 113, Day 127, Day 169, Day 253 and Day 337
measure: Serum Trough Concentration Levels (Ctrough) of Cetuximab
timeFrame: Pre-dose: Day 8, Day 22, Day 29, Day 43, Day 50, Day 64, Day 71, Day 85, Day 99, Day 113, Day 127, Day 169, Day 253 and Day 337
measure: Overall Survival (OS)
timeFrame: Time from the first dose of study drug until occurrence of death due to any cause (assessed up to 941 days)
measure: Number of Participants With Positive Anti-Drug Antibody (ADA) of Avelumab
timeFrame: Pre-dose up to 149 days
measure: Number of Participants With Positive Anti-Drug Antibody (ADA) of Cetuximab
timeFrame: Pre-dose up to 149 days
Other outcomes:
Locations:
city: Budapest
country: Hungary
facility: Semmelweis Egyetem - Pulmonologiai Klinika
city: Debrecen
country: Hungary
facility: Debreceni Egyetem - Tudogyogyaszati Klinika
city: Gyor
country: Hungary
facility: Petz Aladar Megyei Oktato Korhaz - Pulmonologiai Osztaly
city: Szombathely
country: Hungary
facility: Markusovszky Egyetemi Oktatokorhaz
city: Torokbalint
country: Hungary
facility: Tudogyogyintezet Torokbalint - Onkopulmonologiai es Jarobeteg centrum
city: Zalaegerszeg
country: Hungary
facility: Zala Megyei Szent Rafael Korhaz
city: Belgrade
country: Serbia
facility: Clinical Center "Bezanijska kosa" - Department of Oncology
city: Belgrade
country: Serbia
facility: Clinical Center Kragujevac (no dept.)
city: Sremska Kamenica
country: Serbia
facility: Institute for Pulmonary Diseases of Vojvodina
city: A Coruña
country: Spain
facility: Complejo Hospitalario Universitario A Coruña - Servicio de Oncologia
city: Barcelona
country: Spain
facility: Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica
city: Barcelona
country: Spain
facility: Hospital Universitari Vall d'Hebron - Dept of Oncology
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre - Servicio de Oncologia
city: Madrid
country: Spain
facility: Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia
city: Málaga
country: Spain
facility: Hospital Regional Universitario de Malaga
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena - Servicio de Oncologia
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen del Rocio
city: Valencia
country: Spain
facility: Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica
city: Zaragoza
country: Spain
facility: Hospital Clinico Universitario Lozano Blesa - Dept of Oncology
Study officials:
affiliation: Merck KGaA, Darmstadt, Germany
name: Medical Responsible
role: STUDY_DIRECTOR
References: