EGFR Antibody

Necitumumab, IMC-11F8

EGFR Antibody Derived from Baselga J.1

Target

Epidermal growth factor receptor (EGFR) is a member of the EGF family of tyrosine kinases. EGFR activation leads to stimulation of tyrosine kinase-dependent signal transduction pathways that can contribute to neoplastic transformation and tumor growth.2 EGFR is expressed in multiple tumor types and has been correlated with malignant progression, induction of angiogenesis, and inhibition of apoptosis. Inhibition of the EGFR pathway in cells can result in disruption of cell cycle progression, mitosis, and potentiation of apoptosis. The EGFR signaling network is involved in triggering and regulating the malignant growth of many EGFR-expressing tumors of epithelial origin.3

Molecule

Necitumumab (IMC-11F8) is a fully human IgG1 monoclonal antibody designed to bind and block the ligand binding site of EGFR.3

Clinical Development

Necitumumab is being investigated in clinical trials in patients with NSCLC.

ImClone Systems
Schema

A Randomized, Multicenter, Open-Label, Phase 2 Study of Paclitaxel-Carboplatin Chemotherapy Plus Necitumumab (IMC-11F8) vs Paclitaxel-Carboplatin Chemotherapy Alone in the First-line Treatment of Patients With Stage IV Squamous Non-small Cell Lung Cancer (NSCLC)

Key Inclusion Criteria

  • Histologically or cytologically confirmed stage IV squamous NSCLC
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Archived or recent tumor tissue (minimum of 5 unstained tissue slides or a paraffin-embedded tissue block) available for analysis of epidermal growth factor receptor (EGFR) protein expression by immunohistochemistry (IHC) and other biomarker assessments
  • ECOG performance status of ≤1

Key Exclusion Criteria

  • Nonsquamous NSCLC
  • Received prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the EGFR, vascular endothelial growth factor (VEGF), or VEGF receptor
  • Received previous chemotherapy for NSCLC
  • Major surgery or received any investigational therapy in the 4 weeks prior to randomization
  • Chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed)
  • Brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants (participants who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible)

Please visit www.clinicaltrials.gov for more information on this clinical trial [NCT01769391].

Schema

A Single-Arm, Multicenter, Open-Label, Phase 2 Study of Gemcitabine-Cisplatin Chemotherapy Plus Necitumumab (IMC-11F8) in the First-line Treatment of Patients With
Stage IV Squamous Non-small Cell Lung Cancer (NSCLC)

Key Inclusion Criteria

  • Histologically or cytologically confirmed stage IV squamous NSCLC
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • ECOG performance status of ≤1

Key Exclusion Criteria

  • Nonsquamous NSCLC
  • Received prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting the epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF), or VEGF receptor
  • Received previous chemotherapy for NSCLC
  • Major surgery or received any investigational therapy in the 4 weeks prior to study enrollment
  • Chest irradiation within 12 weeks prior to randomization (except palliative irradiation of bone lesions, which is allowed)
  • Brain metastases that are symptomatic or require ongoing treatment with steroids or anticonvulsants (participants who have undergone previous radiotherapy for brain metastases, who are now nonsymptomatic and no longer require treatment with steroids or anticonvulsants, are eligible)

Please visit www.clinicaltrials.gov for more information on this clinical trial [NCT01788566].

Schema

An Open-Label, Multicenter, Phase 1b/2 Study to Evaluate Necitumumab in Combination With Gemcitabine and Cisplatin in the First-line Treatment of Patients With Advanced (Stage IV) Squamous Non-small Cell Lung
Cancer (NSCLC)

Key Inclusion Criteria

  • Stage IV squamous NSCLC
  • Measurable or nonmeasurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • ECOG performance status of ≤1
  • No prior chemotherapy regimen, surgery, or chest radiotherapy

Key Exclusion Criteria

  • Has undergone major surgery within 28 days prior to enrollment or has major surgery planned, or has had subcutaneous venous access device placement within 7 days prior to enrollment
  • Has undergone any prior radiation therapy, except for Gamma Knife radiation and palliative radiation treatment, and at least 14 days have elapsed from last radiation treatment prior to enrollment
  • Has brain metastases that are symptomatic or require surgery, medication, and radiotherapy except Gamma Knife
  • Has diabetes requiring insulin
  • Has significant third-space fluid retention
  • Has history of interstitial pneumonitis
  • Has an ongoing or active infection

Please visit www.clinicaltrials.gov for more information on this clinical trial [NCT01763788].

[NCT00981058]    Lung Cancer    First-line Treatment of Participants With Stage IV Squamous Non-small Cell Lung Cancer With Necitumumab and Gemcitabine-Cisplatin (SQUIRE)