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EGFR Antibody

Necitumumab, LY3012211, IMC-11F8

Tags: cancer cell signaling, lung cancer, phase II, phase I

EGFR Antibody Derived from Yarden Y and Shilo BZ.1

Target

Epidermal growth factor receptor (EGFR) is a member of the ErbB (erythroblastic leukemia viral oncogene homolog) family of receptor tyrosine kinases. EGFR activation occurs in response to ligand stimulation and/or genetic alterations of the EGFR gene, such as somatic mutations, amplifications, or deletions. Activated EGFR induces downstream signaling through the MAPK (mitogen-activated protein kinases), PI3K/AKT (phosphoinositide 3-kinase/v-Akt murine thymoma viral oncogene) and PLCY (phospholipase CY) signal transduction pathways that mediate cell proliferation, cell survival, and cell migration, respectively, thereby contributing to neoplastic transformation and tumor growth.2,3

Molecule

Necitumumab (IMC-11F8) is a recombinant IgG1 human monoclonal antibody designed to bind and block the ligand binding site of EGFR.4-6

Clinical Development

Necitumumab is being investigated in clinical trials in patients with non-small cell lung cancer and in a combination clinical trial in immuno-oncology.

ImClone Systems
NCT01763788 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
  • Eastern Cooperative Oncology Group (ECOG) performance status of ≤1
  • No prior chemotherapy regimen, surgery, or chest radiotherapy

Key Exclusion Criteria

  • Major surgery within 28 days prior to enrollment, major surgery planned, or subcutaneous venous access device placement within 7 days prior to enrollment
  • 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
  • Brain metastases that are symptomatic or require surgery, medication, or radiotherapy except Gamma Knife
  • Diabetes requiring insulin
  • Significant third-space fluid retention
  • History of interstitial pneumonitis
  • Ongoing or active infection

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

NCT02392507 Schema

A Single-Arm, Multicenter, Open-Label, Phase 2 Study of Nab®-Paclitaxel and Carboplatin Chemotherapy Plus Necitumumab (LY3012211) in the First-line Treatment of Patients With Stage IV Squamous Non-small Cell Lung Cancer (NSCLC)*

Key Inclusion Criteria

  • Stage IV squamous NSCLC at the time of study entry
  • Measurable disease at the time of study enrollment, as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • Tumor tissue available for analysis of EGFR protein expression by immunohistochemistry

Key Exclusion Criteria

  • Nonsquamous NSCLC
  • Received prior anticancer therapy with monoclonal antibodies, signal transduction inhibitors, or any therapies targeting EGFR, vascular endothelial growth factor (VEGF), or VEGF receptor
  • Received previous chemotherapy for advanced NSCLC
  • Major surgery or any investigational therapy in the 4 weeks prior to study entry
  • Received systemic radiotherapy within 4 weeks prior to study entry or focal radiotherapy within 2 weeks prior to study entry
  • Symptomatic central nervous system malignancy or metastasis

Please visit www.clinicaltrials.gov for more information on this clinical trial [NCT02392507].

*Clinical trial conducted in partnership with Celgene.

NCT02411591 Schema

A Single-Arm, Multicenter, Phase 1b Study With an Expansion Cohort to Evaluate Safety and Efficacy of Necitumumab in Combination With Abemaciclib in Treatment of Patients With Stage IV Non-small Cell Lung Cancer (NSCLC)

Key Inclusion Criteria

  • Histologically or cytologically confirmed stage IV NSCLC:
    -
    Part A: Stage IV NSCLC (any type)
    -
    Part B: Stage IV NSCLC (squamous and nonsquamous)
  • Measurable disease as defined by Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
  • The participant must have progressed after platinum-based chemotherapy and have received 1 other prior chemotherapy for advanced and/or metastatic disease or must be judged by the physician as ineligible for further standard second-line chemotherapy. Prior treatment with EGFR-tyrosine kinase inhibitor and anaplastic lymphoma kinase (ALK) inhibitors is mandatory in participants whose tumor has EGFR-activating mutations or ALK translocations. Prior vascular endothelial growth factor (VEGF)/VEGF receptor-targeting agents and neoadjuvant/adjuvant therapies are permitted
  • The participant has tumor tissue available for biomarker analyses
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1
  • Adequate organ function

Key Exclusion Criteria

  • Currently enrolled in a clinical trial involving an investigational product or nonapproved use of a drug or device. Prior treatment with cyclin-dependent kinase 4 and 6-targeting or necitumumab is not permitted
  • Serious concomitant systemic disorder or significant cardiac disease
  • Major surgery or received any investigational therapy in the 30 days prior to study enrollment
  • Chest irradiation within 4 weeks prior to receiving study treatment
  • Brain metastases that are symptomatic
  • History of arterial or venous embolism within 3 months prior to study enrollment. If the embolism occurred >3 and <6 months, the participant is eligible provided appropriate treatment according to local standard is ensured
  • Any ongoing or active infection
  • Known hypersensitivity to any of the treatment components
  • Concurrent active malignancy
  • History of interstitial lung disease

Please visit www.clinicaltrials.gov for more information on this clinical trial [NCT02411591].

NCT02451930 Schema

A Single-Arm, Multicenter, Phase 1b Study With an Expansion Cohort to Evaluate Safety and Efficacy of the Combination of Necitumumab With Pembrolizumab in Patients With Stage IV Non-small Cell Lung Cancer (NSCLC)*

Key Inclusion Criteria

  • Stage IV NSCLC
    -
    Part A: NSCLC stage IV (any type)
    -
    Part B: NSCLC stage IV (squamous and nonsquamous)
  • The patient must have progressed after 1 platinum-based chemotherapy regimen for stage IV disease. Prior treatment with EGFR-tyrosine kinase inhibitor and anaplastic lymphoma kinase (ALK) inhibitors is mandatory in patients whose tumor has an EGFR or ALK mutation. Prior vascular endothelial growth factor (VEGF)/VEGR receptor-targeting agents and neoadjuvant/adjuvant therapies are permitted
  • Presence of measurable disease as defined by Response Evaluation Criteria In Solid Tumors (RECIST) version 1.1
  • Evaluable tumor tissue available for biomarker analyses
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1

Key Exclusion Criteria

  • Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, anti-cytotoxic T lymphocyte-associated antigen-4 antibody, or EGFR-directed monoclonal antibody
  • Serious concomitant systemic disorder or significant cardiac disease.
  • Major surgery or received any investigational therapy in the 30 days prior to study enrollment
  • Brain metastases that are symptomatic
  • Concurrent active malignancy
  • History of interstitial lung disease, pneumonitis, or autoimmune disease or syndrome that requires steroids or immunosuppressive agents

Please visit www.clinicaltrials.gov for more information on this clinical trial [NCT02451930].

*Clinical trial conducted in partnership with Merck.

[NCT01769391]    Lung Cancer    A Study of Necitumumab and Chemotherapy in Participants With Stage IV Squamous Non-small Cell Lung Cancer