Study of Avelumab and Cetuximab Plus Gemcitabine and Cisplatin in Participants With NSCLC

NCT ID: NCT03717155

Last Updated: 2022-06-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 43 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-30
• Study Completion Date: 2021-05-27

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).

Conditions

Squamous Non-Small Cell Lung Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Avelumab and Cetuximab

Participants received 800 milligrams Avelumab, 1250 milligrams per square meter (mg/m\^2) gemcitabine on Day 1 and Day 8, cisplatin at a dose of 75 mg/m\^2 on Day 1 along with 250 mg/m2 body surface area Cetuximab on Day 1 and 500 mg/m2 body surface area on Day 8 of each cycle as intravenous (IV) infusions up to maximum of 4 cycles (each cycle is of 3 weeks) until disease progression or unacceptable toxicities. In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles. Subsequently participants were administered with avelumab and cetuximab as IV infusion at the dose of 800 mg and 500 mg/m\^2 respectively, every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.

Group Type: EXPERIMENTAL

Avelumab

Intervention Type: DRUG

Participants received avelumab intravenous infusions at a dose of 800 milligram (mg) on Day 1 and Day 8 of each 3-week cycle for the first 4 cycles. Thereafter, administered every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.

Cetuximab

Intervention Type: DRUG

Participants received cetuximab intravenous infusions at a dose of 250 milligram per meter square (mg/m\^2) body surface area on Day 1 and 500 mg/m\^2 body surface area on Day 8 of first 4 cycles of concurrent chemotherapy. Thereafter, administered given at a dose of 500 mg/m\^2 intravenous every 2 weeks in the Maintenance phase, until disease progression or unacceptable toxicities.

Gemcitabine

Intervention Type: DRUG

Participants received gemcitabine intravenous infusions at a dose of 1250 mg/m\^2 body surface area on Day 1 and Day 8 in 3-week cycles up to a maximum of 4 cycles, until disease progression or unacceptable toxicities.

Cisplatin

Intervention Type: DRUG

Participants received cisplatin intravenous infusions at a dose of 75 mg/m\^2 body surface area on Day 1 of 3-week cycles up to a maximum of 4 cycles, until disease progression or unacceptable toxicities.

Carboplatin

Intervention Type: DRUG

In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles.

Interventions

Avelumab

Participants received avelumab intravenous infusions at a dose of 800 milligram (mg) on Day 1 and Day 8 of each 3-week cycle for the first 4 cycles. Thereafter, administered every 2 weeks in the Maintenance phase until disease progression or unacceptable toxicities.

Intervention Type: DRUG

Cetuximab

Participants received cetuximab intravenous infusions at a dose of 250 milligram per meter square (mg/m\^2) body surface area on Day 1 and 500 mg/m\^2 body surface area on Day 8 of first 4 cycles of concurrent chemotherapy. Thereafter, administered given at a dose of 500 mg/m\^2 intravenous every 2 weeks in the Maintenance phase, until disease progression or unacceptable toxicities.

Intervention Type: DRUG

Gemcitabine

Participants received gemcitabine intravenous infusions at a dose of 1250 mg/m\^2 body surface area on Day 1 and Day 8 in 3-week cycles up to a maximum of 4 cycles, until disease progression or unacceptable toxicities.

Intervention Type: DRUG

Cisplatin

Participants received cisplatin intravenous infusions at a dose of 75 mg/m\^2 body surface area on Day 1 of 3-week cycles up to a maximum of 4 cycles, until disease progression or unacceptable toxicities.

Intervention Type: DRUG

Carboplatin

In case of cisplatin toxicities, participants were switched to carboplatin at a dose of target area under the serum concentration-time curve of 5 (AUC 5) on Day 1 for the remainder of cycles.

Intervention Type: DRUG

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

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Merck KGaA, Darmstadt, Germany

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Medical Responsible

Role: STUDY_DIRECTOR

Merck KGaA, Darmstadt, Germany

Locations

Semmelweis Egyetem - Pulmonologiai Klinika

Budapest, , Hungary

Debreceni Egyetem - Tudogyogyaszati Klinika

Debrecen, , Hungary

Petz Aladar Megyei Oktato Korhaz - Pulmonologiai Osztaly

Győr, , Hungary

Markusovszky Egyetemi Oktatokorhaz

Szombathely, , Hungary

Tudogyogyintezet Torokbalint - Onkopulmonologiai es Jarobeteg centrum

Törökbálint, , Hungary

Zala Megyei Szent Rafael Korhaz

Zalaegerszeg, , Hungary

Clinical Center "Bezanijska kosa" - Department of Oncology

Belgrade, , Serbia

Clinical Center Kragujevac (no dept.)

Belgrade, , Serbia

Institute for Pulmonary Diseases of Vojvodina

Kamenitz, , Serbia

Complejo Hospitalario Universitario A Coruña - Servicio de Oncologia

A Coruña, , Spain

Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica

Barcelona, , Spain

Hospital Universitari Vall d'Hebron - Dept of Oncology

Barcelona, , Spain

Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica

Madrid, , Spain

Hospital Universitario 12 de Octubre - Servicio de Oncologia

Madrid, , Spain

Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia

Madrid, , Spain

Hospital Regional Universitario de Malaga

Málaga, , Spain

Hospital Universitario Virgen Macarena - Servicio de Oncologia

Seville, , Spain

Hospital Universitario Virgen del Rocio

Seville, , Spain

Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica

Valencia, , Spain

Hospital Clinico Universitario Lozano Blesa - Dept of Oncology

Zaragoza, , Spain

Countries

Hungary; Serbia; Spain

References

Andric Z, Galffy G, Cobo Dols M, Szima B, Stojanovic G, Petrovic M, Felip E, Vicente Baz D, Ponce Aix S, Juan-Vidal O, Szalai Z, Losonczy G, Calles Blanco A, Bernabe R, Garcia Ledo G, Aguilar Hernandez A, Duecker K, Zhou D, Schroeder A, Guezel G, Ciardiello F. Avelumab in Combination With Cetuximab and Chemotherapy as First-Line Treatment for Patients With Advanced Squamous NSCLC. JTO Clin Res Rep. 2023 Jan 2;4(2):100461. doi: 10.1016/j.jtocrr.2022.100461. eCollection 2023 Feb.

Reference Type: DERIVED

PMID: 36718142 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Related Links

https://clinicaltrials.emdgroup.com/en/trial-details/?id=MS201944_0170

Trial Awareness and Transparency website

https://www.merckgroup.com/en/company/contact-us/medinfo-contact-map.html

Medical Information Location Map - Med Info Contacts

Other Identifiers

2018-001529-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

MS201944_0170

Identifier Type: -

Identifier Source: org_study_id