VECTIBIX

Panitumumab (ABX-EGF) is a recombinant human IgG2 monoclonal antibody that binds specifically to the human epidermal growth factor receptor (EGFR).

This drug is an antineoplastic agent.

Panitumumab was granted

FDA approval on 27 September 2006.

For the treatment of

EGFR-expressing, metastatic colorectal carcinoma that is refractory to fluoropyrimidine-, oxaliplatin-, and irinotecan.

• containing chemotherapy regimens.

Panitumumab is a recombinant, human IgG2 kappa monoclonal antibody that binds specifically to the human Epidermal Growth Factor Receptor (EGFR).

EGFR is a transmembrane glycoprotein that belongs to the subfamily of type I receptor tyrosine kinases.

EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, including those of the colon and rectum.

Interaction of

EGFR with its normal ligands causes phosphorylation and activation of a series of intracellular proteins that will in turn regulate the transcription of genes involved with cellular growth and survival, motility, and prolieration.

Signal transduction through

EGFR leads to the activation of the wild type KRAS gene, but the presence of an activating somatic mutation of the KRAS gene within a cancer cell can result in the dysregulation of signaling pathways and resistance to EGFR inhibitor therapy.

days (range: 4-11 days).

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Panitumumab was shown to cause skin, ocular and mucosal related toxicities in 90% of patients receiving panitumumab.

Subsequent to the development of severe dermatologic toxicities, infectious complications, including sepsis, septic death, and abscesses requiring incisions and drainage, were reported.

Wild-Type mCRC

Administer 6 mg/kg every 14 days as an intravenous infusion over 60 minutes (≤ 1000 mg) or 90 minutes (> 1000 mg).

G12C -mutated mCRC: Administer 6 mg/kg every 14 days as an intravenous infusion over 60 minutes (≤ 1000 mg) or 90 minutes (> 1000 mg) in combination with sotorasib. 2.1 Patient Selection RAS Wild-Type mCRC Prior to initiation of treatment with Vectibix as monotherapy, assess RAS mutational status in colorectal tumors and confirm the absence of a RAS mutation in exon 2 (codons and 13), exon 3 (codons and 61), and exon 4 (codons and 146) of both KRAS and NRAS.

G12C-mutated mCRC Prior to initiation of treatment with Vectibix in combination with sotorasib, confirm the presence of the KRAS G12C mutation using an FDA-approved test.

Information on FDA-approved tests for the detection of RAS mutations in patients with mCRC is available at: 2.2 Recommended Dosage RAS Wild-Type mCRC The recommended dosage of Vectibix is 6 mg/kg, administered as an intravenous infusion every 14 days until disease progression or unacceptable toxicity.

Appropriate medical resources for the treatment of severe infusion reactions should be available during Vectibix infusions.

G12C -mutated mCRC Administer the first sotorasib dose prior to the first Vectibix infusion.

The recommended dosage for

Vectibix in combination with sotorasib is 6 mg/kg, administered as an intravenous infusion every 14 days until disease progression, unacceptable toxicity, or until sotorasib is withheld or discontinued.

Refer to the sotorasib full prescribing information for recommended sotorasib dosing information.

Appropriate medical resources for the treatment of severe infusion reactions should be available during Vectibix infusions. 2.3 Dose Modifications Dose Modifications for Vectibix in Combination with Sotorasib When Vectibix is administered in combination with sotorasib, if treatment with sotorasib is temporarily withheld or permanently discontinued, temporarily withhold or permanently discontinue Vectibix, respectively.

Refer to the sotorasib full prescribing information for dose modifications for adverse reactions associated with the use of sotorasib.

Dose Modifications for Specific Adverse Reactions Associated with the Use of Vectibix Infusion Reactions Reduce infusion rate by 50% in patients experiencing a mild or moderate (Grade 1 or 2) infusion reaction for the duration of that infusion.

Terminate the infusion in patients experiencing severe infusion reactions.

Depending on the severity and/or persistence of the reaction, permanently discontinue Vectibix.

Dermatologic Toxicity Upon first occurrence of a Grade 3 (NCI-CTC/CTCAE) dermatologic reaction, withhold to 2 doses of Vectibix.

If the reaction improves to < Grade 3, reinitiate Vectibix at the original dose.

Upon the second occurrence of a

Grade 3 (NCI-CTC/CTCAE) dermatologic reaction, withhold to 2 doses of Vectibix.

If the reaction improves to < Grade 3, reinitiate Vectibix at 80% of the original dose.

Upon the third occurrence of a

If the reaction improves to < Grade 3, reinitiate Vectibix at 60% of the original dose.

Upon the fourth occurrence of a

Grade 3 (NCI-CTC/CTCAE) dermatologic reaction, permanently discontinue Vectibix.

Permanently discontinue Vectibix following the occurrence of a Grade 4 dermatologic reaction or for a Grade 3 (NCI-CTC/CTCAE) dermatologic reaction that does not recover after withholding 1 or 2 doses. 2.4 Preparation and Administration For intravenous infusion only.

Do not administer

Vectibix as an intravenous push or bolus.

Visually inspect parenteral drug products for particulate matter and discoloration prior to administration.

Vectibix solution is colorless and may contain a small amount of visible translucent-to-white, amorphous, proteinaceous particles.

Do not use if the solution is discolored or cloudy, or if foreign matter is present.

Prepare the solution for infusion, using aseptic technique, as follows: Do not shake the vial.

Use a 21-gauge or larger gauge (smaller bore) hypodermic needle to withdraw the necessary amount of Vectibix for a dose of 6 mg/kg. Do not use needle-free devices (e.g., vial adapters) to withdraw vial contents.

Dilute to a total volume of 100 mL with 0.9% sodium chloride injection, USP.

Doses higher than 1000 mg should be diluted to 150 mL with 0.9% sodium chloride injection, USP.

Do not exceed a final concentration of 10 mg/mL.

Mix diluted solution by gentle inversion.

Discard any unused portion of the vial.

Administer using a low-protein-binding 0.2 µm or 0.22 µm in-line filter.

Vectibix must be administered via infusion pump.

Flush line before and after

Vectibix administration with 0.9% sodium chloride injection, USP, to avoid mixing with other drug products or intravenous solutions.

Do not mix

Vectibix with, or administer as an infusion with, other medicinal products.

Do not add other medications to solutions containing panitumumab.

Infuse doses of 1000 mg or lower over 60 minutes through a peripheral intravenous line or indwelling intravenous catheter.

If the first infusion is tolerated, administer subsequent infusions over to 60 minutes.

Administer doses higher than 1000 mg over 90 minutes.

Use the diluted infusion solution of

Vectibix within 6 hours of preparation if stored at room temperature, or within 24 hours of dilution if stored at 2° to 8°C (36° to 46°F).

Vectibix is supplied as a sterile, colorless, preservative-free solution containing 20 mg/mL panitumumab in a single-dose vial.

Vectibix is provided as one vial per carton.

Each 5 mL single-dose vial contains 100 mg of panitumumab in 5 mL (20 mg/mL) (NDC 55513-954-01, NDC 55513-954-21).

Each 20 mL single-dose vial contains 400 mg of panitumumab in 20 mL (20 mg/mL) (NDC 55513-956-01, NDC 55513-956-21).

Store vials in the original carton under refrigeration at 2° to 8°C (36° to 46°F) until time of use.

Protect from direct sunlight.

Do not freeze or shake.

Discard any unused portion remaining in the vial.

Store vials in the original carton under refrigeration at 2° to 8°C (36° to 46°F) until time of use.

Protect from direct sunlight.

Do not freeze or shake.

Discard any unused portion remaining in the vial.

Based on data from animal studies and its mechanism of action, Vectibix can cause fetal harm when administered to pregnant women.

Limited available data on the use of Vectibix in pregnant women are not sufficient to inform a risk of adverse pregnancy-related outcomes.

Vectibix is a human

IgG monoclonal antibody and may be transferred across the placenta during pregnancy.

Reproduction studies in cynomolgus monkeys treated with 1.25 to 5 times the recommended human dose of panitumumab resulted in significant embryolethality and abortions; however, no other evidence of teratogenesis was noted in offspring.

Advise pregnant women of the potential risk to the fetus.

In the

U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Based on animal models, EGFR is involved in prenatal development and may be essential for normal organogenesis, proliferation, and differentiation in the developing embryo.

Pregnant cynomolgus monkeys were treated weekly with panitumumab during the period of organogenesis (gestation day [GD] 20-50).

While no panitumumab was detected in serum of neonates from panitumumab-treated dams, anti-panitumumab antibody titers were present in of 27 offspring delivered at GD 100.

There were no fetal malformations or other evidence of teratogenesis noted in the offspring; however, significant increases in embryolethality and abortions occurred at doses of approximately 1.25 to 5 times the recommended human dose (based on body weight).

The safety and effectiveness of

Vectibix have not been established in pediatric patients.

The pharmacokinetics of panitumumab at doses ranging from 2.5 mg/kg intravenous weekly, 6 mg/kg intravenous every 2 weeks, or 9 mg/kg intravenous every 3 weeks were evaluated in 28 pediatric patients.

Panitumumab exposures were comparable in adult and adolescent patients of to 17 years of age.

Limited data suggested that pediatric patients of to < 12 years of age had lower panitumumab exposure and higher clearance than that in adolescent patients following 6 mg/kg intravenous administration of Vectibix.

There was no evidence of an anti-tumor treatment effect in these patients.

Of the 737 patients who received Vectibix monotherapy for recurrent or refractory mCRC, 36% were and over while 8% were and over.

No overall differences in safety or efficacy were observed in elderly patients (≥ 65 years of age) treated with Vectibix monotherapy.

Of the 322 patients who received Vectibix plus FOLFOX, for wild-type KRAS -mutated mCRC, 128 (40%) were and over while 8% were and over.

Patients older than 65 years of age experienced an increased incidence of serious adverse events (52% vs 36%) and an increased incidence of serious diarrhea (15% vs 5%) as compared to younger patients.

In a pooled analysis of 132 patients who received Vectibix in combination with sotorasib 960 mg for KRAS G12C-mutated mCRC, 30% were and over while 9% were and over.

No overall differences in safety or efficacy were observed in elderly patients (≥ 65 years of age) compared to younger patients treated with Vectibix in combination with sotorasib.