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NCT01763788

A Study of Necitumumab in the First-Line Treatment of Stage IV Squamous Non-Small Cell Lung Cancer (NSCLC)

Completed Phase 1, PHASE2 Results posted Last updated 25 October 2019
What this trial tests

Phase 1, PHASE2 trial testing Necitumumab in Squamous Non-small Cell Lung Cancer in 192 participants. Completed in 17 October 2018.

Timeline
7 May 2013
Primary endpoint
28 June 2017
17 October 2018

Quick facts

Lead sponsorEli Lilly and Company
PhasePhase 1, PHASE2
StatusCompleted
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingnone
Primary purposetreatment
Enrollment192
Start date7 May 2013
Primary completion28 June 2017
Estimated completion17 October 2018
Sites20 locations across Japan

Drugs / interventions tested

Conditions studied

Sponsor

Eli Lilly and Company — full company profile →

Who can join

20 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.

Phase 1b: Number of Participants With Dose Limiting Toxicities (DLTs) Primary · Day 1 to Day 21 in Cycle 1 (Up To 21 days)

DLT was defined as any of the following events graded according to the National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version 4.0, when the event occurred within 21 days from Day 1 in Cycle 1 and was considered to be definitely or probably related to necitumumab and/or gemcitabine-cisplatin chemotherapy: Grade 4 neutropenia ≥ 7 days, Grade ≥ 3 febrile neutropenia except for transient febrile neutropenia (Grade 3 neutropenia with fever ≥ 38.5 degrees Celsius (°C) for ≤ 24 hours), Grade 3 thrombocytopenia requiring platelet substitution, Grade 4 thrombocyt

GroupValue95% CI
Phase 1b: Cohort 10
Phase 1b: Cohort 20
Phase 2: Overall Survival (OS) Primary · From Date of Randomization until Death Due to Any Cause (Up To 39 Months)

OS defined as the time from the date of randomization to the date of death due to any cause. Participants who are alive at the time of study completion or are lost to follow-up will be censored at the time they were last known to be alive.

GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)14.9213.37 – 18.17
Phase 2: GC (Gemcitabine, Cisplatin)10.848.90 – 14.39
Phase 2: Progression Free Survival (PFS) Secondary · From Date of Randomization to Measured Progressive Disease or Death Due to Any Cause (Up To 39 Months)

PFS defined as time from date of randomization until first radiographic documentation of measured progressive disease(PD) defined by response evaluation criteria in solid tumors (RECIST) v1.1 or death from any cause. PD was at least 20% increase in sum of diameters of target lesions with reference being smallest sum on study and an absolute increase of at least 5 mm,or unequivocal progression of non-target lesions,or 1 or more new lesions.If participant does not have complete baseline disease assessment,PFS time censored at date of randomization,regardless of whether or not objectively determi

GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)4.214.14 – 4.27
Phase 2: GC (Gemcitabine, Cisplatin)4.013.52 – 4.17
Phase 1b: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR]) Secondary · Baseline to Measured Progressive Disease (Up To 39 Months)

ORR was the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of nontarget lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference be

GroupValue95% CI
Phase 1b: Cohort 10.00.0 – 0.0
Phase 1b: Cohort 283.353.5 – 100.0
Phase 2: Percentage of Participants Who Achieve Best Overall Tumor Response of Complete Response or Partial Response (Objective Tumor Response Rate [ORR]) Secondary · Baseline to Measured Progressive Disease (Up To 39 Months)

ORR was the percentage of participants achieving a best overall response of complete response (CR) or partial response (PR) as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. CR defined as the disappearance of all target and non-target lesions and no appearance of new lesions. PR defined as at least a 30% decrease in the sum of the longest diameters (LD) of target lesions (taking as reference the baseline sum LD), no progression of nontarget lesions, and no appearance of new lesions. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference be

GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)51.140.8 – 61.4
Phase 2: GC (Gemcitabine, Cisplatin)20.912.5 – 29.2
Phase 2: Time to Treatment Failure (TTF) Secondary · From Date of Randomization to Measured Progressive Disease, Death Due to Any Cause, Discontinuation of Treatment or Initiation of New Anticancer Therapy (Up To 39 Months)

TTF was time from the date of randomization until the date of the first observation of radiographically documented progressive disease (PD), death due to any cause, discontinuation of treatment for any reason, or initiation of new anticancer therapy. PD was at least a 20% increase in the sum of the diameters of target lesions, with reference being the smallest sum on study and an absolute increase of at least 5 mm, or unequivocal progression of non-target lesions, or 1 or more new lesions. Time to treatment failure was censored at the date of the last follow-up visit for participants who did n

GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)4.164.01 – 4.24
Phase 2: GC (Gemcitabine, Cisplatin)3.752.92 – 4.01
Phase 2: Change From Baseline in EuroQol 5-Dimensional 3 Level (EuroQol-5D-3L) Index Score Secondary · Baseline, Cycle 4 (Cycle = 3 weeks)

EQ-5D measures mobility, self-care, usual activities, pain/discomfort, anxiety/depression. 3 severity levels: no, some, severe problems. The index score was calculated from a set of item weights to derive a score on a theoretical scale of 0 to 1, with 1 representing the best health status and zero representing death based on item weights for the Japanese population. One Cycle = 3 weeks and it can be delayed up to 6 weeks.

GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)0.04± 0.16
Phase 2: GC (Gemcitabine, Cisplatin)0.03± 0.17
Phase 2: Change From Baseline in EuroQol 5-Dimensional 3 Level (EuroQol-5D-3L) Visual Analog Scale (VAS) Secondary · Baseline, Cycle 4 (Cycle = 3 weeks)

EQ-5D VAS allowed participants to rate their present health condition. Possible scores ranged from 0 (worst imaginable health state) to 100 (best imaginable health state). One Cycle = 3 weeks and it can be delayed up to 6 weeks.

GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)7.81± 18.90
Phase 2: GC (Gemcitabine, Cisplatin)11.10± 18.03
Phase 2: Change From Baseline in Lung Cancer Symptom Scale (LCSS) Secondary · Baseline, Cycle 4 (Cycle = 3 weeks)

The LCSS is a validated and reliable instrument to assess lung cancer-specific symptoms and their impact on QOL.The LCSS total score was defined as the mean of the 9 items of the scale and the average symptom burden index (ASBI) is defined as the mean of 6 symptom-specific lung cancer questions. Each of the 9 symptom or summary items is assessed on a 100-mm visual analogue scale (VAS), with 0 representing no symptoms or better QOL.

Loss of Appetite
GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)-4.48± 26.20
Phase 2: GC (Gemcitabine, Cisplatin)-9.03± 29.32
Fatigue
GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)-5.42± 26.63
Phase 2: GC (Gemcitabine, Cisplatin)-4.02± 26.47
Cough
GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)-18.00± 24.17
Phase 2: GC (Gemcitabine, Cisplatin)-15.82± 30.59
Dyspnea
GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)-5.14± 22.51
Phase 2: GC (Gemcitabine, Cisplatin)-5.08± 24.51
Hemoptysis
GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)-4.75± 21.75
Phase 2: GC (Gemcitabine, Cisplatin)-4.10± 16.46
Pain
GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)-10.68± 22.07
Phase 2: GC (Gemcitabine, Cisplatin)-12.38± 26.99
Overall Symptoms
GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)-11.62± 23.20
Phase 2: GC (Gemcitabine, Cisplatin)-9.56± 24.61
Interference
GroupValue95% CI
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)-6.92± 26.70
Phase 2: GC (Gemcitabine, Cisplatin)-5.93± 29.78
Phase 1b: Pharmacokinetics (PK): Maximum Concentration (Cmax) of Necitumumab Secondary · Cycle 1 (C1) Day 1 (D1) and C3 D1: Predose, End-of-infusion and 1, 3, 6, 24, 96, 168 h post-end-of-infusion

The Cmax is observed maximum serum concentration, taken directly from the serum concentration-time profile.

Cycle 1
GroupValue95% CI
Phase 1b: Cohort 1454± 6
Phase 1b: Cohort 2371± 32
Cycle 3
GroupValue95% CI
Phase 1b: Cohort 2372± 15
Phase 1b: PK: Cmax of Gemcitabine and Cisplatin Secondary · Gemcitabine: Cycle 1(C1) Day1(D1): Predose, End-of-infusion and 0.5, 1, 2 h post-end-of-infusion; Cisplatin:C1 D1: Predose, End-of-infusion and 3, 21, 93, 165 h post-end-of-infusion

The Cmax is observed maximum plasma concentration, taken directly from the plasma concentration-time profile.

Gemcitabine
GroupValue95% CI
Phase 1b: Cohort 117400± 8
Phase 1b: Cohort 226000± 16
Cisplatin
GroupValue95% CI
Phase 1b: Cohort 13740± 14
Phase 1b: Cohort 23980± 10
Phase 1b: PK: Area Under the Serum Concentration-Time Curve From Time Zero to Infinite Time (AUC[0-infinity]) of Necitumumab Secondary · Cycle 1 (C1) Day 1 (D1) and C3 D1: Predose, End-of-infusion and 1, 3, 6, 24, 96, 168 h post-end-of-infusion

The AUC(0-infinity) is area under the serum concentration-time curve from time zero to infinite time.

Cycle 1
GroupValue95% CI
Phase 1b: Cohort 1NA± NA
Phase 1b: Cohort 238900± 28

Adverse events — posted to ClinicalTrials.gov

Time frame: Up To 39 Months. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Phase 1b: Cohort 1
Serious: 1/3 (33%)
Deaths: 0/3
Phase 1b: Cohort 2
Serious: 0/6 (0%)
Deaths: 0/6
Phase 2: GC+N (Gemcitabine, Cisplatin + Necitumumab)
Serious: 32/90 (36%)
Deaths: 63/90
Phase 2: GC (Gemcitabine, Cisplatin)
Serious: 22/91 (24%)
Deaths: 74/91

Serious adverse events (48 terms)

ReactionSystemPhase 1b: Cohort 1Phase 1b: Cohort 2Phase 2: GC+N (Gemcitabine…Phase 2: GC (Gemcitabine, …
Febrile neutropeniaBlood and lymphatic system disorders
PneumoniaInfections and infestations
Lung infectionInfections and infestations
Decreased appetiteMetabolism and nutrition disorders
Lower gastrointestinal haemorrhageGastrointestinal disorders
Deep vein thrombosisVascular disorders
Bone marrow toxicityBlood and lymphatic system disorders
ThrombocytopeniaBlood and lymphatic system disorders
Abdominal herniaGastrointestinal disorders
DiarrhoeaGastrointestinal disorders
Diverticular perforationGastrointestinal disorders
Duodenal ulcerGastrointestinal disorders
Gastric ulcerGastrointestinal disorders
Gastric ulcer haemorrhageGastrointestinal disorders
Gastrointestinal haemorrhageGastrointestinal disorders
FatigueGeneral disorders
PainGeneral disorders
PyrexiaGeneral disorders
AppendicitisInfections and infestations
DiverticulitisInfections and infestations
InfectionInfections and infestations
Retroperitoneal abscessInfections and infestations
Septic shockInfections and infestations
Urinary tract infectionInfections and infestations
Compression fractureInjury, poisoning and procedural complications
Other adverse events (290 terms — click to expand)

ReactionSystemPhase 1b: Cohort 1Phase 1b: Cohort 2Phase 2: GC+N (Gemcitabine…Phase 2: GC (Gemcitabine, …
Dermatitis acneiformSkin and subcutaneous tissue disorders
Decreased appetiteMetabolism and nutrition disorders
ConstipationGastrointestinal disorders
NauseaGastrointestinal disorders
AnaemiaBlood and lymphatic system disorders
Neutrophil count decreasedInvestigations
Platelet count decreasedInvestigations
White blood cell count decreasedInvestigations
HiccupsRespiratory, thoracic and mediastinal disorders
Dry skinSkin and subcutaneous tissue disorders
ParonychiaInfections and infestations
StomatitisGastrointestinal disorders
HypomagnesaemiaMetabolism and nutrition disorders
MalaiseGeneral disorders
DiarrhoeaGastrointestinal disorders
HyponatraemiaMetabolism and nutrition disorders
DysgeusiaNervous system disorders
InsomniaPsychiatric disorders
PyrexiaGeneral disorders
Alanine aminotransferase increasedInvestigations
AlopeciaSkin and subcutaneous tissue disorders
VomitingGastrointestinal disorders
FatigueGeneral disorders
Aspartate aminotransferase increasedInvestigations
NeutropeniaBlood and lymphatic system disorders
Weight decreasedInvestigations
HypoalbuminaemiaMetabolism and nutrition disorders
EpistaxisRespiratory, thoracic and mediastinal disorders
Upper respiratory tract infectionInfections and infestations
HyperkalaemiaMetabolism and nutrition disorders
Rash maculo-papularSkin and subcutaneous tissue disorders
Oedema peripheralGeneral disorders
Blood creatinine increasedInvestigations
RashSkin and subcutaneous tissue disorders
Blood alkaline phosphatase increasedInvestigations
HypocalcaemiaMetabolism and nutrition disorders
Tumour painNeoplasms benign, malignant and unspecified (incl cysts and polyps)
HypertensionVascular disorders
Lung infectionInfections and infestations
PruritusSkin and subcutaneous tissue disorders

Most-reported serious reactions: Febrile neutropenia, Pneumonia, Lung infection, Decreased appetite, Lower gastrointestinal haemorrhage, Deep vein thrombosis, Bone marrow toxicity, Thrombocytopenia.

Data from ClinicalTrials.gov NCT01763788 adverse events section.

Sponsor's own description

The purpose of the Phase 1b portion of the study is to investigate how the body tolerates necitumumab, in combination with gemcitabine and cisplatin chemotherapy as first line treatment in participants with Stage IV squamous NSCLC and to determine the recommended dose for the subsequent Phase 2 portion of the study. The purpose of the Phase 2 portion of the study is to evaluate the efficacy of necitumumab in combination with gemcitabine and cisplatin chemotherapy in participants with Stage IV squamous NSCLC in a first-line setting.

Publications & conference data

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

  1. Trial Watch: Tumor-targeting monoclonal antibodies in cancer therapy.
    Vacchelli E, Aranda F, Eggermont A, Galon J, et al · · 2014 · cited 54× · PMID 24605265 · DOI 10.4161/onci.27048
  2. Immunotherapy for non-small cell lung cancer: current concepts and clinical trials.
    Mayor M, Yang N, Sterman D, Sterman D, et al · · 2016 · cited 27× · PMID 26516195 · DOI 10.1093/ejcts/ezv371
  3. Necitumumab plus gemcitabine and cisplatin versus gemcitabine and cisplatin alone as first-line treatment for stage IV squamous non-small cell lung cancer: A phase 1b and randomized, open-label, multicenter, phase 2 trial in Japan.
    Watanabe S, Yoshioka H, Sakai H, Hotta K, et al · · 2019 · cited 26× · PMID 30797492 · DOI 10.1016/j.lungcan.2019.01.005
  4. Trends in patient-reported outcome use in early phase dose-finding oncology trials - an analysis of ClinicalTrials.gov.
    Lai-Kwon J, Yin Z, Minchom A, Yap C. · · 2021 · cited 23× · PMID 34676991 · DOI 10.1002/cam4.4307
  5. Association between skin toxicity and efficacy of necitumumab in squamous non-small-cell lung cancer: a pooled analysis of two randomized clinical trials-SQUIRE and JFCM.
    Watanabe S, Yoshioka H, Sakai H, Hotta K, et al · · 2024 · cited 2× · PMID 38520847 · DOI 10.1016/j.esmoop.2024.102975

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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/NCT01763788.

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