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Squamous Non-Small Cell Lung CancerPhase 2NCT03717155

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

A Phase 2 study testing Avelumab, Cetuximab and Gemcitabine in people with Squamous Non-Small Cell Lung Cancer, run by Merck KGaA, Darmstadt, Germany at 20 sites in 3 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Squamous Non-Small Cell Lung Cancer
What is being tested?
Avelumab, Cetuximab and Gemcitabine
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
43 participants
Where
20 sitesin 3 countries
Study dates
30 Oct 2018to 27 May 2021
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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

Who cannot join

  • 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)
Show all 17Show fewer
  • 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

Trial locations and contacts

20 sites in 3 countries.

20 sites in 3 countries

Spain11 sites

  • Complejo Hospitalario Universitario A Coruña - Servicio de Oncologia

    A Coruña, 15006

  • Hospital Universitari Quiron Dexeus - Servicio de Oncologia Medica

    Barcelona, 08028

  • Hospital Universitari Vall d'Hebron - Dept of Oncology

    Barcelona, 08035

  • Hospital General Universitario Gregorio Marañon - Servicio de Oncologia Medica

    Madrid, 28007

  • Hospital Universitario 12 de Octubre - Servicio de Oncologia

    Madrid, 28041

  • Hospital Universitario HM Madrid Sanchinarro - Servicio de Oncologia

    Madrid, 28050

  • Hospital Regional Universitario de Malaga

    Málaga, 29010

  • Hospital Universitario Virgen Macarena - Servicio de Oncologia

    Seville, 41009

  • Hospital Universitario Virgen del Rocio

    Seville

  • Hospital Universitari i Politecnic La Fe - Servicio de Oncologia Medica

    Valencia, 46026

  • Hospital Clinico Universitario Lozano Blesa - Dept of Oncology

    Zaragoza, 50009

Other trials in Spain

Hungary6 sites

  • Semmelweis Egyetem - Pulmonologiai Klinika

    Budapest, 1125

  • Debreceni Egyetem - Tudogyogyaszati Klinika

    Debrecen, 4032

  • Petz Aladar Megyei Oktato Korhaz - Pulmonologiai Osztaly

    Győr, 9024

  • Markusovszky Egyetemi Oktatokorhaz

    Szombathely, 9700

  • Tudogyogyintezet Torokbalint - Onkopulmonologiai es Jarobeteg centrum

    Törökbálint, 2045

  • Zala Megyei Szent Rafael Korhaz

    Zalaegerszeg, 8900

Other trials in Hungary

Serbia3 sites

  • Clinical Center "Bezanijska kosa" - Department of Oncology

    Belgrade

  • Clinical Center Kragujevac (no dept.)

    Belgrade

  • Institute for Pulmonary Diseases of Vojvodina

    Kamenitz

Other trials in Serbia

About this study

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

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).

Keywords
Avelumab, Cetuximab, Cisplatin, Gemcitabine, Non-Small Cell Lung Cancer
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AvelumabDrug

    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.

  • CetuximabDrug

    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.

  • GemcitabineDrug

    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.

  • CisplatinDrug

    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.

  • CarboplatinDrug

    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.

Study groups in NCT03717155
Study groupRoleWhat they receive
Avelumab and CetuximabExperimentalParticipants 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.
Receives: Drug: Avelumab; Drug: Cetuximab; Drug: Gemcitabine; Drug: Cisplatin; Drug: Carboplatin

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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)

  1. 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)

    Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug.Serious adverse event (SAE) was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. TEAE is defined as AEs starting or worsening after the first intake of the study drug. TEAEs include both Serious and non-serious TEAEs. irAEs included AEs that matches a preferred term on the list of pre-selected MedDRA terms. AEs with relationship to study treatment are reported as Treatment-related AEs. Treatment related AEs with grade 3 or more is also reported.

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

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

    Progression free survival (PFS) is defined as the time (in months) from first treatment day to the date of the first documentation of objective progression of disease (PD) according to RECIST version 1.1 assessed by Investigator, or death due to any cause, whichever occurs first. PD is defined as at least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

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

  3. Duration of Response (DOR)

    DOR is defined for participants with confirmed complete response (CR) or partial response (PR), as the time from first documentation of confirmed response to the date of first documentation of progression of disease (PD) according to RECIST version 1.1 (assessed by Investigator) or death due to any cause or tumor assessment. Duration of objective response was assessed using Kaplan-Meier analysis. CR: Disappearance of all evidence of target and non-target lesions. PR: At least 30% reduction from baseline in the SLD of all lesions. PD: At least a 20 percent (%) increase in the SLD, taking as reference the smallest SLD recorded from baseline or the appearance of 1 or more new lesions.

    Measured: 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)

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

    Ceoi is the serum concentration observed immediately at the end of infusion. This was taken directly from the observed Avelumab concentration-time data.

    Measured: 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

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

    Ceoi is the serum concentration observed immediately at the end of infusion. This was taken directly from the observed cetuximab concentration-time data.

    Measured: 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

  6. Serum Trough Concentration Levels (Ctrough) of Avelumab

    Ctrough is the serum concentration observed immediately before next dosing.

    Measured: 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

  7. Serum Trough Concentration Levels (Ctrough) of Cetuximab

    Ctrough is the serum concentration observed immediately before next dosing.

    Measured: 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

  8. Overall Survival (OS)

    OS is defined as the time from the first treatment day to the date of death due to any cause. Overall survival was assessed using Kaplan-Meier analysis.

    Measured: Time from the first dose of study drug until occurrence of death due to any cause (assessed up to 941 days)

  9. Number of Participants With Positive Anti-Drug Antibody (ADA) of Avelumab

    The detection of antibodies to avelumab was performed using a validated immunoassay method with tiered testing of screening, confirmatory and titration. Number of participants with positive anti-drug antibody (ADA) of avelumab were reported.

    Measured: Pre-dose up to 149 days

  10. Number of Participants With Positive Anti-Drug Antibody (ADA) of Cetuximab

    The detection of antibodies to cetuximab was performed using a validated immunoassay method with tiered testing of screening, confirmatory and titration. Number of participants with positive anti-drug antibody (ADA) of cetuximab were reported.

    Measured: Pre-dose up to 149 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Oct 2018
  2. Study start30 Oct 2018
  3. Primary completion30 Sep 2020
  4. Study completion27 May 2021

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
43 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03717155
Sponsor's protocol ID
MS201944_0170
Other IDs
2018-001529-24, 2018
Status last verified
Apr 2022
First submitted
22 Oct 2018
Last updated
6 Jun 2022
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • 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.

    PubMed 36718142

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Avelumab, Cetuximab and Gemcitabine in people with Squamous Non-Small Cell Lung Cancer, run by Merck KGaA, Darmstadt, Germany at 20 sites in 3 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 17 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 6 Jun 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 20 sites in Spain, Hungary, Serbia. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Nov 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome 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 (time frame: Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 612 days)). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03717155, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Jun 2022.

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