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NCT03717155

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

Completed Phase 2 Results posted Last updated 6 June 2022
What this trial tests

Phase 2 trial testing Avelumab in Squamous Non-Small Cell Lung Cancer in 43 participants. Completed in 27 May 2021.

Timeline
30 October 2018
Primary endpoint
30 September 2020
27 May 2021

Quick facts

Lead sponsorMerck KGaA, Darmstadt, Germany
PhasePhase 2
StatusCompleted
Study typeINTERVENTIONAL
Allocationna
Designsingle group
Maskingnone
Primary purposetreatment
Enrollment43
Start date30 October 2018
Primary completion30 September 2020
Estimated completion27 May 2021
Sites20 locations across Serbia, Spain, Hungary

Drugs / interventions tested

Conditions studied

Sponsor

Merck KGaA, Darmstadt, Germany — full company profile →

Who can join

18 and older, any sex, with Squamous Non-Small Cell Lung Cancer. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Percentage of Participants With Confirmed Best Objective Response (BOR) According to Response Evaluation Criteria In Solid Tumors (RECIST) Version 1.1 Assessed by Investigator Primary · Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 612 days)

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 b

GroupValue95% CI
Avelumab and Cetuximab34.921.0 – 50.9
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) Secondary · Time from the first dose of study drug assessed up to (941 days)

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

TEAEs
GroupValue95% CI
Avelumab and Cetuximab41
Treatment-Related AEs
GroupValue95% CI
Avelumab and Cetuximab38
Treatment Related Grade>=3 TEAEs
GroupValue95% CI
Avelumab and Cetuximab24
irTEAEs
GroupValue95% CI
Avelumab and Cetuximab13
Progression-Free Survival (PFS) Time Per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 Secondary · Time from the first dose of study drug until occurrence of PD, death due to any cause (assessed up to 737 days)

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.

GroupValue95% CI
Avelumab and Cetuximab6.14.3 – 9.0
Duration of Response (DOR) Secondary · 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)

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 ref

GroupValue95% CI
Avelumab and Cetuximab7.14.2 – 12.5
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Avelumab Secondary · 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

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

Day 1
GroupValue95% CI
Avelumab and Cetuximab206± 26.6
Day 8
GroupValue95% CI
Avelumab and Cetuximab243± 23.8
Day 22
GroupValue95% CI
Avelumab and Cetuximab234± 24.1
Day 29
GroupValue95% CI
Avelumab and Cetuximab282± 26.8
Day 43
GroupValue95% CI
Avelumab and Cetuximab237± 30.5
Day 50
GroupValue95% CI
Avelumab and Cetuximab259± 38.9
Day 64
GroupValue95% CI
Avelumab and Cetuximab214± 67.6
Day 71
GroupValue95% CI
Avelumab and Cetuximab244± 43.8
Immediate Observed Serum Concentration at End of Infusion (Ceoi) of Cetuximab Secondary · 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

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

Day 1
GroupValue95% CI
Avelumab and Cetuximab109± 50.7
Day 8
GroupValue95% CI
Avelumab and Cetuximab198± 86.6
Day 22
GroupValue95% CI
Avelumab and Cetuximab124± 54.4
Day 29
GroupValue95% CI
Avelumab and Cetuximab260± 25.0
Day 43
GroupValue95% CI
Avelumab and Cetuximab154± 32.7
Day 50
GroupValue95% CI
Avelumab and Cetuximab238± 28.9
Day 64
GroupValue95% CI
Avelumab and Cetuximab159± 36.1
Day 71
GroupValue95% CI
Avelumab and Cetuximab262± 25.1
Serum Trough Concentration Levels (Ctrough) of Avelumab Secondary · 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

Ctrough is the serum concentration observed immediately before next dosing.

Day 8
GroupValue95% CI
Avelumab and Cetuximab28.8± 82.7
Day 22
GroupValue95% CI
Avelumab and Cetuximab13.6± 97.1
Day 29
GroupValue95% CI
Avelumab and Cetuximab42.4± 147.8
Day 43
GroupValue95% CI
Avelumab and Cetuximab15.6± 115.1
Day 50
GroupValue95% CI
Avelumab and Cetuximab56.4± 77.9
Day 64
GroupValue95% CI
Avelumab and Cetuximab19.7± 145.7
Day 71
GroupValue95% CI
Avelumab and Cetuximab58.2± 62.5
Day 85
GroupValue95% CI
Avelumab and Cetuximab21.5± 70.9
Serum Trough Concentration Levels (Ctrough) of Cetuximab Secondary · 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

Ctrough is the serum concentration observed immediately before next dosing.

Day 8
GroupValue95% CI
Avelumab and Cetuximab12.1± 90.0
Day 22
GroupValue95% CI
Avelumab and Cetuximab12.8± 63.7
Day 29
GroupValue95% CI
Avelumab and Cetuximab22.8± 73.3
Day 43
GroupValue95% CI
Avelumab and Cetuximab25.6± 103.7
Day 50
GroupValue95% CI
Avelumab and Cetuximab23.9± 118.1
Day 64
GroupValue95% CI
Avelumab and Cetuximab17.2± 157.9
Day 71
GroupValue95% CI
Avelumab and Cetuximab35.4± 110.4
Day 85
GroupValue95% CI
Avelumab and Cetuximab26.5± 119.4
Overall Survival (OS) Secondary · Time from the first dose of study drug until occurrence of death due to any cause (assessed up to 941 days)

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.

GroupValue95% CI
Avelumab and Cetuximab10.18.6 – 14.5
Number of Participants With Positive Anti-Drug Antibody (ADA) of Avelumab Secondary · Pre-dose up to 149 days

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.

GroupValue95% CI
Avelumab and Cetuximab7
Number of Participants With Positive Anti-Drug Antibody (ADA) of Cetuximab Secondary · Pre-dose up to 149 days

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.

GroupValue95% CI
Avelumab and Cetuximab1

Adverse events — posted to ClinicalTrials.gov

Time frame: Time from the first dose of study drug until 941 days.. Reporting threshold: 5%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Avelumab and Cetuximab
Serious: 20/43 (47%)
Deaths: 30/43

Serious adverse events (21 terms)

ReactionSystemAvelumab and Cetuximab
Disease progressionGeneral disorders
AnaemiaBlood and lymphatic system disorders
NeutropeniaBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
DeathGeneral disorders
Non-cardiac chest painGeneral disorders
Anaphylactic reactionImmune system disorders
Lower respiratory tract infectionInfections and infestations
PneumoniaInfections and infestations
Blood creatinine increasedInvestigations
DehydrationMetabolism and nutrition disorders
HypomagnesaemiaMetabolism and nutrition disorders
Back painMusculoskeletal and connective tissue disorders
SeizureNervous system disorders
Acute kidney injuryRenal and urinary disorders
Renal failureRenal and urinary disorders
Renal impairmentRenal and urinary disorders
Dry gangreneVascular disorders
Femoral artery embolismVascular disorders
Peripheral artery thrombosisVascular disorders
TachycardiaCardiac disorders
Other adverse events (32 terms — click to expand)

ReactionSystemAvelumab and Cetuximab
RashSkin and subcutaneous tissue disorders
AnaemiaBlood and lymphatic system disorders
HypomagnesaemiaMetabolism and nutrition disorders
NeutropeniaBlood and lymphatic system disorders
NauseaGastrointestinal disorders
AstheniaGeneral disorders
ThrombocytopeniaBlood and lymphatic system disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
Decreased appetiteMetabolism and nutrition disorders
PyrexiaGeneral disorders
Alanine aminotransferase increasedInvestigations
LeukopeniaBlood and lymphatic system disorders
DiarrhoeaGastrointestinal disorders
Amylase increasedInvestigations
Blood creatinine increasedInvestigations
HyponatraemiaMetabolism and nutrition disorders
Aspartate aminotransferase increasedInvestigations
Transaminases increasedInvestigations
CoughRespiratory, thoracic and mediastinal disorders
Oedema peripheralGeneral disorders
NasopharyngitisInfections and infestations
Respiratory tract infectionInfections and infestations
Neutrophil count decreasedInvestigations
HypocalcaemiaMetabolism and nutrition disorders
HypophosphataemiaMetabolism and nutrition disorders
DyspnoeaRespiratory, thoracic and mediastinal disorders
DermatitisSkin and subcutaneous tissue disorders
Dry skinSkin and subcutaneous tissue disorders
ErythemaSkin and subcutaneous tissue disorders
Dermatitis acneiformSkin and subcutaneous tissue disorders
ArthralgiaMusculoskeletal and connective tissue disorders

Most-reported serious reactions: Disease progression, Anaemia, Neutropenia, Thrombocytopenia, Death, Non-cardiac chest pain, Anaphylactic reaction, Lower respiratory tract infection.

Data from ClinicalTrials.gov NCT03717155 adverse events section.

Sponsor's own description

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).

Publications & conference data

5 peer-reviewed publications reference this trial (live from Europe PMC):

  1. Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation.
    Wu M, Huang Q, Xie Y, Wu X, et al · · 2022 · cited 336× · PMID 35279217 · DOI 10.1186/s13045-022-01242-2
  2. Emerging therapies for non-small cell lung cancer.
    Zhang C, Leighl NB, Wu YL, Zhong WZ. · · 2019 · cited 115× · PMID 31023335 · DOI 10.1186/s13045-019-0731-8
  3. Achievements and futures of immune checkpoint inhibitors in non-small cell lung cancer.
    Qiu Z, Chen Z, Zhang C, Zhong W. · · 2019 · cited 32× · PMID 31463163 · DOI 10.1186/s40164-019-0143-z
  4. Keynote 407: the combination of pembrolizumab and chemotherapy cracks the shell of squamous cell lung cancer.
    Viteri S, Cabrera-Gálvez C, Rosell R. · · 2020 · cited 4× · PMID 32676347 · DOI 10.21037/tlcr-20-400
  5. Avelumab in Combination With Cetuximab and Chemotherapy as First-Line Treatment for Patients With Advanced Squamous NSCLC.
    Andric Z, Gálffy G, Cobo Dols M, Szima B, et al · · 2023 · PMID 36718142 · DOI 10.1016/j.jtocrr.2022.100461

Verify or expand the search:

Other trials of Avelumab

Trials testing the same drug.

Other recruiting trials for Squamous Non-Small Cell Lung Cancer

Currently open trials in the same condition.

Other Merck KGaA, Darmstadt, Germany trials

Trials by the same sponsor.

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Data sources for this page

Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT03717155.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing