Vectibix is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human Epidermal Growth Factor Receptor (EGFR). Overexpression of EGFR is detected in many human cancers, including those of the colon and rectum. When Vectibix binds to EGFR it competitively inhibits the binding of ligands for EGFR. This results in inhibition of cell growth, induction of apoptosis, decreased pro-inflammatory cytokine and vascular growth factor production.

Vectibix is specifically indicated for for the treatment of EGFR-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan- containing chemotherapy regimens.

Vectibix is supplied as a sterile, colorless, preservative-free solution containing 20 mg/mL designed for intravenous infusion. The recommended initial dose of the drug is 6 mg/kg administered over 60 minutes as an intravenous infusion every 14 days. If safety or tolerability concerns arise, dosage may be reduced by 50%. Doses higher than 1000 mg should be infused over 90 minutes.

FDA Approval
FDA approval of Vectibix was based on the results of one clinical trial. This open-label, multinational, randomized, controlled trial enrolled 463 subjects with EGFR-expressing, metastatic carcinoma of the colon or rectum (mCRC). Subjects were randomized to receive Vectibix at a dose of 6 mg/kg given once every 2 weeks plus best supportive care (BSC) (n = 231) or BSC alone (n = 232) until disease progression. Statistical significance was seen in prolongation of progression free survival for the subjects treated with Vectibix versus those treated with BSC alone, with a mean of 96 days versus 60 days, respectively.

Ongoing Study Commitments

• Amgen has agreed to submit a final study report for study 20050181, entitled, "A Randomized, Multicenter Phase 3 Study to Compare the Efficacy of Panitumumab in Combination with Chemotherapy to the Efficacy of Chemotherapy Alone in Patients with Previously Treated Metastatic Colorectal Cancer."
  Protocol Accepted: May 2006
  Study Start: June 2006
  Final Report Submission: March 2010
• Amgen has agreed to conduct a Phase 1 study, Protocol 20050252 entitled, "A Phase 1 Study to Evaluate the Safety and Pharmacokinetics of Panitumumab in Children with Refractory Solid Tumors" in children and adolescents (up to 18 yr of age)
  Protocol Submission: July 2007
  Study Start: October 2007
  Final Report Submission: October 2011
• Amgen has agreed to conduct a phase 2 study to further assess the safety and to estimate the anti-tumor activity of Panitumumab in pediatric patients with solid tumors.
  Protocol Submission: August 2011
  Study Start: December 2011
  Final Report Submission: May 2014
• Amgen has agreed to submit a summary of the final results of overall survival (OS), with 12-month minimal follow up from Study 20020408, entitled, "An Open Label Randomized, Phase 3 Clinical Trial of ABX-EGF Plus Best Supportive Care Versus Best Supportive Care in Subjects With Metastatic Colorectal Cancer."
  Final Report Submission: September 2007
• Amgen has agreed to submit interim and final clinical study reports based on data obtained in study 20050181, entitled, "A Randomized, Multicenter Phase 3 Study to Compare the Efficacy of Panitumumab in Combination with Chemotherapy to the Efficacy of Chemotherapy Alone in Patients with Previously Treated Metastatic Colorectal Cancer."
  Protocol Submitted: May 2006
  Study Started: June 2006
  Final Report Submission: March 2010
• Amgen has agreed to submit interim and final clinical study reports based on data obtained in study 20050181, entitled, "A Randomized, Multicenter Phase 3 Study to Compare the Efficacy of Panitumumab in Combination with Chemotherapy to the Efficacy of Chemotherapy Alone in Patients with Previously Treated Metastatic Colorectal Cancer."
  Protocol Submitted: May 2006
  Study Started: June 2006
  Final Report Submission: March 2010
• Amgen has agreed to submit a final study report for study 20050184, entitled "A Phase 2, Open-label, Randomized Clinical Trial of Skin Toxicity Treatment of Subjects Receiving Second-line FOLFIR or Irinotecan Only Chemotherapy Concomitantly with Panitumumab."
  Protocol submitted: March 2006
  Study Started: April 2006
  Final Report Submission: November 2008
• Amgen has agreed to conduct a Phase 1 drug interaction study 20062010, entitled "Open Label, 2-Cohort, Randomized Study to Assess the Potential Pharmacokinetic Drug-Drug Interaction between Irinotecan and Panitumumab in Subjects with Colorectal Cancer."
  Protocol Submission: August 2007
  Study Start: December 2007
  Final Report Submission: August 2009
• Amgen has agreed to submit a final study report for study 20040192 entitled, "A Phase 1 Clinical Study of ABX-EGF (Panitumumab) Evaluation of the Safety and PK of ABX-EGF in Japanese Subjects with Advanced Solid Tumors."
  Final Report Submission: April 2007

Adverse events associated with the use of Vectibix may include, but are not limited to, the following:

• Dermatological toxicities
• Ocular toxicities
• Hypomagnesemia
• Fatigue
• Abdominal pain
• Nausea
• Diarrhea
• Constipation

In addition, Vectibix was shown to cause skin, ocular and mucosal related toxicities in 90% of patients receiving Vectibix. Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death, and abscesses requiring incisions and drainage, were reported. It is recommended that patients wear sunscreen and hats and limit sun exposure while receiving Vectibix since sunlight can exacerbate any skin reactions that may occur.

Vectibix binds specifically to EGFR on both normal and tumor cells, and competitively inhibits the binding of ligands for EGFR. Nonclinical studies show that binding of panitumumab to the EGFR prevents ligand-induced receptor autophosphorylation and activation of receptor-associated kinases, resulting in inhibition of cell growth, induction of apoptosis, decreased pro-inflammatory cytokine and vascular growth factor production, and internalization of the EGFR.

Wainberg Z, Hecht JR Panitumumab in colon cancer: a review and summary of ongoing trials. Expert opinion on biological therapy. 2006 Nov;6(11):1229-35.

Saif MW, Cohenuram M Role of panitumumab in the management of metastatic colorectal cancer. Clinical Colorectal Cancer 2006 Jul;6(2):118-24

Gibson TB, Ranganathan A, Grothey A Randomized phase III trial results of panitumumab, a fully human anti-epidermal growth factor receptor monoclonal antibody, in metastatic colorectal cancer. Clinical colorectal cancer 2006 May;6(1):29-31.

Tyagi P Recent results and ongoing trials with panitumumab (ABX-EGF), a fully human anti-epidermal growth factor receptor antibody, in metastatic colorectal cancer Clinical colorectal cancer 2005 May;5(1):21-3.

For additional information regarding Vectibix or colorectal cancer, please visit the Vectibix web page.