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

NCT03717155 | Completed Phase 2 Results

• 2 other identifiers: MS201944_01702018-001529-24
• Study Type: interventional
• Target: 43
• Locations: 3 countries
• Sites: 20

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

Keywords

Avelumab; Cetuximab; Cisplatin; Gemcitabine; Non-Small Cell Lung Cancer

Outcome Measures

Primary Outcomes (1)

• Percentage of Participants With Confirmed Best Objective Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Assessed by Investigator

  Confirmed BOR was defined as the percentage of participants who achieved confirmed complete responses (CR) or partial response (PR), according to RECIST version 1.1 assessed by the Investigator.CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30 percent (%) reduction from baseline in the sum of the longest diameter (SLD) of all lesions. Stable disease (SD)= Neither sufficient increase to qualify for progression of disease (PD) nor sufficient shrinkage to qualify for PR. PD: At least a 20 % increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions. Confirmed CR=as at least two determinations of CR at least 4 weeks apart with no PD. Confirmed PR=as at least 2 determinations of PR or better (PR followed by PR or PR followed by CR), at least 4 weeks apart (not qualifying for a CR) with no PD in between. Percentage of Participants with confirmed BOR were reported.

  Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 612 days)

Secondary Outcomes (10)

• 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)

  Time from the first dose of study drug assessed up to (941 days)

• Progression-Free Survival (PFS) Time Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1

  Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 737 days)

• Duration of Response (DOR)

  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)

• Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab

  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

• Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab

  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

Study Arms (1)

Avelumab and Cetuximab

EXPERIMENTAL

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.

Drug: Avelumab; Drug: Cetuximab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin

Interventions

Avelumab 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.

Avelumab and Cetuximab

Cetuximab 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.

Avelumab and Cetuximab

Gemcitabine 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.

Avelumab and Cetuximab

Cisplatin 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.

Avelumab and Cetuximab

Carboplatin 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.

Avelumab and Cetuximab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Merck KGaA, Darmstadt, Germany: lead

Study Sites (20)

Semmelweis Egyetem - Pulmonologiai Klinika

Budapest, 1125, Hungary

Location

Debreceni Egyetem - Tudogyogyaszati Klinika

Debrecen, 4032, Hungary

Location

Petz Aladar Megyei Oktato Korhaz - Pulmonologiai Osztaly

Győr, 9024, Hungary

Location

Markusovszky Egyetemi Oktatokorhaz

Szombathely, 9700, Hungary

Location

Tudogyogyintezet Torokbalint - Onkopulmonologiai es Jarobeteg centrum

Törökbálint, 2045, Hungary

Location

Zala Megyei Szent Rafael Korhaz

Zalaegerszeg, 8900, Hungary

Location

Clinical Center "Bezanijska kosa" - Department of Oncology

Belgrade, Serbia

Location

Clinical Center Kragujevac (no dept.)

Belgrade, Serbia

Location

Institute for Pulmonary Diseases of Vojvodina

Kamenitz, Serbia

Location

Complejo Hospitalario Universitario A Coruña - Servicio de Oncologia

A Coruña, 15006, Spain

Location

Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica

Barcelona, 08028, Spain

Location

Hospital Universitari Vall d'Hebron - Dept of Oncology

Barcelona, 08035, Spain

Location

Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica

Madrid, 28007, Spain

Location

Hospital Universitario 12 de Octubre - Servicio de Oncologia

Madrid, 28041, Spain

Location

Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia

Madrid, 28050, Spain

Location

Hospital Regional Universitario de Malaga

Málaga, 29010, Spain

Location

Hospital Universitario Virgen Macarena - Servicio de Oncologia

Seville, 41009, Spain

Location

Hospital Universitario Virgen del Rocio

Seville, Spain

Location

Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica

Valencia, 46026, Spain

Location

Hospital Clinico Universitario Lozano Blesa - Dept of Oncology

Zaragoza, 50009, Spain

Location

Related Publications (1)

• 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.

  PMID: 36718142 DERIVED

Related Links

• Trial Awareness and Transparency website
• Medical Information Location Map - Med Info Contacts

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

avelumab; Cetuximab; Gemcitabine; Cisplatin; Carboplatin

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Heterocyclic Compounds; Deoxycytidine; Cytidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Coordination Complexes; Organic Chemicals

Results Point of Contact

• Title: Communication Center
• Organization: Merck KGaA, Darmstadt, Germany

service@emdgroup.com

+49-6151-72-5200

Study Officials

• Medical Responsible

  Merck KGaA, Darmstadt, Germany

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 22, 2018
• First Posted: October 24, 2018
• Study Start: October 30, 2018
• Primary Completion: September 30, 2020
• Study Completion: May 27, 2021
• Last Updated: June 6, 2022
• Results First Posted: November 9, 2021

Record last verified: 2022-04

Locations

HU (6); SE (3); ES (11)