What is Braftovi?

Braftovi (encorafenib) is a prescription medication manufactured by Array BioPharma that is approved to treat specific cancers in conjunction with either Mektovi (binimetinib) or Erbitux (cetuximab).

Braftovi and Mektovi are kinase inhibitors that, together, are indicated to treat melanoma (skin cancer) that has: 1) spread to other parts of the body, 2) cannot be removed by surgery, and 3) has the abnormal “BRAF” gene. More specifically they treat unresectable or metastatic melanoma with a V600K mutation or BRAF V600E mutation. You will take an FDA-approved test to confirm you have one of these mutations before beginning treatment.

If Braftovi and Erbitux are used together, they are indicated to treat adults with colorectal cancer (cancer of the colon or rectum) that has: 1) the abnormal “BRAF” gene, 2) has recently been treated, and 3) has already spread to other parts of the body.

Braftovi is not meant to treat you if you have wild-type BRAF colorectal cancer or wild-type BRAF melanoma. You will most likely have to take tests to see if Braftovi is right for you. It is unknown whether Braftovi is effective and safe in children.

Braftovi is part of the Pfizer Oncology Together program, available to US patients, that offers personalized support to patients using Pfizer Oncology medications.

How does Braftovi work?

Braftovi is a kinase inhibitor indicated to treat BRAF-mutant melanoma or metastatic colorectal cancer. Encorafenib, the active ingredient in Braftovi, targets different kinases in the tumor’s RAF/MEK/ERK pathways, suppressing them, and ultimately slowing and stopping the growth of the cancer cells.

What doses of Braftovi are available?

Braftovi comes in 75mg capsules for oral administration. For melanoma, the recommended dose is 450 mg orally, once daily in combination with Mektovi. The recommended dose for metastatic colorectal cancer (CRC) is usually 300 mg orally once daily in combination with Erbitux.

How do you use Braftovi?

Make sure that you take Braftovi exactly as your healthcare provider tells you. Read the medication guide and full prescribing information before taking Braftovi. Braftovi is a pill that you take by mouth once a day.

You can take Braftovi with or without food. If you miss a dose, take Braftovi as soon as you remember. However, if it is closer to (within 12 hours of) your next dose, skip that dose and take your next dose at the regular time. If you vomit after taking your dose, do not take an extra dose. Instead, wait and take your next dose at your scheduled time.

Your Braftovi dose will most likely change if you stop treatment with Erbitux or Mektovi. Make sure to talk to your healthcare provider when there are any changes to other medications.

You will often have to take various FDA-approved tests before, during, and after treatment.

What are the side effects of Braftovi?

The most common side effects of Braftovi were found in the Columbus clinical trial that compared Braftovi (and Braftovi + Mektovi) to vemurafenib. In the Columbus clinical trial, they tested Braftovi’s efficacy by measuring the progression-free survival (PFS), overall survival (OS), and overall response rate (ORR) of the drug. In this trial, they found that the clinically significant side effects of Braftovi include:

Nausea
Fatigue
Acne-like rash (dermatitis acneiform)
Abdominal pain
Diarrhea
Constipation
Visual impairment
Pain or swelling of your joints (arthralgia)
Rash
Decreased appetite
Pancreatitis
Anemia

Rarely, Braftovi may cause some serious adverse reactions, according to the Columbus clinical study, including:

New primary malignancies. Most commonly, basal cell carcinoma or cutaneous squamous cell carcinoma.
- Dermatologic evaluations should be made prior to treatment, every two months during treatment, and six months after treatment.
- Dose modification is not recommended for new primary cutaneous malignancies.
- Braftovi, however, may promote malignancies connected to the activation of RAS through mutation or other avenues, resulting in non-cutaneous malignancies.
  - If you do become RAS mutation-positive for non-cutaneous malignancy, Braftovi should be discontinued.
- Be aware of the following symptoms to tell your healthcare provider immediately:
  - Reddish bump that bleeds or does not heal
  - Any skin sores
  - New wart
  - Change in color or size of a mole
Bleeding problems
- Braftovi can cause serious bleeding problems, including in your brain or stomach, that can be life-threatening. Call your healthcare provider and get medical help right away if you have signs of bleeding, including:
  - Cough up blood or blood clots
  - Headaches, feeling weak, or dizziness
  - Black or stools that look like tar
  - Vomit blood or your vomit that looks like "coffee grounds"
Eye problems, especially in the retina
- Call your healthcare provider immediately if you develop any of the following symptoms:
  - See colored dots
  - Blurred vision, vision changes, or loss of vision
  - Eye pain, redness, or swelling
  - See halos (blurred outlines around objects)
QT Prolongation (changes in the electrical activity of your heart)
- QT prolongation can be life-threatening. Tell your healthcare provider right away if you feel:
  - Lightheaded
  - Faint
  - Dizzy
  - An irregular or fast heartbeat
- Your healthcare provider will mostly likely do tests before you start taking Braftovi and during treatment to check if you have enough electrolytes (body salts) to continue with treatment.
Embryo-fetal toxicity
- There is a risk of fetal harm when administered to pregnant women. Use non-hormonal birth control. See the precautions section for more information.
- Males able to reproduce may become infertile when using Braftovi. Talk to your doctor about what is best for you.
Hemorrhage
Growth in BRAF wild-type tumors
- Braftovi does not treat BRAF wild-type tumors. There is evidence of paradoxical activation of MAP-kinase signaling and then increased creation of cells in BRAF wild-type tumors that are exposed to BRAF inhibitors.

Other possible severe adverse events that occurred in patients taking Braftovi and Mektovi (binimetinib) together include:

Interstitial Lung Disease (ILD)
- Occurred in patients with BRAF mutation-positive melanoma
Rhabdomyolysis (muscle breakdown)
- Occurred in patients with BRAF mutation-positive melanoma
Uveitis (inflammation inside your eyes)

Contact your healthcare professional for medical advice about any possible adverse effects you experience while taking Braftovi. You can report your adverse effects to the U.S. Food and Drug Administration at 1-800-FDA-1088 or www.fda.gov/medwatch.

Braftovi drug interactions

When Braftovi is taken with other prescription drugs, over-the-counter medications, vitamins, and supplements, it may change how they work or increase the frequency or severity of side effects. Some drug interactions with Braftovi include:

Strong or moderate CYP3A4 inhibitors
- Avoid coadministration of Braftovi with CYP3A4 inhibitors.
- This includes grapefruit juice; avoid grapefruit juice.
Hormonal contraceptives
- Hormonal contraceptives with Braftovi will change the levels of Braftovi in your body.
Drugs that prolong the QT or QTc interval.

Braftovi precautions

You should be sure that your healthcare provider is aware of all your medical conditions, including if you have:

Eye problems
Had bleeding problems
Low blood levels of potassium, calcium, or magnesium
Heart problems
- Including QT syndrome
Liver or kidney problems
A pregnancy or plan to become pregnant. Braftovi has the possibility of harming your unborn baby.
- If you are a female who is able to become pregnant, you should use an effective form of non-hormonal birth control while taking Braftovi and for two weeks after your final dose of Braftovi.
  - Hormonal birth control should be avoided while taking Braftovi. Talk to your healthcare provider about birth control methods that would work best for you during this time.
- Your healthcare provider will most likely do a pregnancy test before you start taking Braftovi.
- Tell your healthcare provider right away if you do become pregnant or think you might be pregnant while taking Braftovi.
A plan to breastfeed or are breastfeeding. It is unknown whether Braftovi passes into your breast milk. You should not breastfeed while in treatment with Braftovi or for two weeks after your final dose. Talk to your healthcare provider about what is best for you and your baby during this time.

Is there a generic available for Braftovi?

Currently, there is no generic available for Braftovi in the United States.

How do you store Braftovi?

Store at 20°C - 25°C (68°F - 77°F). However, Braftovi can withstand temperatures between 15°C - 30°C (59°F - 86°F).

Do not use it if the safety seal is broken or missing. Dispense in original bottle under local guidance. Protect from moisture and keep the capsules in a container that is tightly closed.