Tovorafenib

OJEMDA is indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation. This indication is approved under accelerated approval based on response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s). OJEMDA is a kinase inhibitor indicated for the treatment of patients 6 months of age and older with relapsed or refractory pediatric low-grade glioma (LGG) harboring a BRAF fusion or rearrangement, or BRAF V600 mutation.

Tovorafenib is a Type II RAF kinase inhibitor of mutant BRAF V600E, wild-type BRAF, and wild-type CRAF kinases. Tovorafenib exhibited antitumor activity in cultured cells and xenograft tumor models harboring BRAF V600E and V600D mutations, and in a xenograft model harboring a BRAF fusion.

Confirm the presence of BRAF fusion or rearrangement, or BRAF V600 mutation prior to initiation of treatment with OJEMDA. Recommended dosage of OJEMDA is based on body surface area. Administer OJEMDA orally, once weekly, with or without food. Tablets: Swallow tablets whole with water. Do not chew, cut, or crush. For Oral Suspension: See full prescribing information for preparation and administration instructions.

None. None.

Hemorrhage: Major hemorrhagic events can occur during treatment with OJEMDA. Withhold, resume at reduced dose, or permanently discontinue based on severity. Skin Toxicity Including Photosensitivity: Advise patients to monitor for new or worsening skin reactions. Advise patients to limit direct ultraviolet exposure and use precautionary measures such as sunscreen, sunglasses and/or protective clothing during treatment with OJEMDA. Withhold, reduce the dose or permanently discontinue based on severity. Hepatotoxicity: OJEMDA can cause hepatotoxicity. Monitor liver function tests prior to administration and during treatment. Effect on Growth: Reductions in growth velocity have been reported. Routinely monitor growth in pediatric patients. Embryo-Fetal Toxicity: Can cause fetal harm. Advise of the potential risk to a fetus and to use effective nonhormonal contraception.

The following clinically significant adverse reactions are described elsewhere in the labeling: Hemorrhage Skin Toxicity Including Photosensitivity Hepatotoxicity Effect on Growth The most common adverse reactions (≥30%) were rash, hair color changes, fatigue, viral infection, vomiting, headache, hemorrhage, pyrexia, dry skin, constipation, nausea, dermatitis acneiform, and upper respiratory tract infection. The most common Grade 3 or 4 laboratory abnormalities (≥2%) were decreased phosphate, decreased hemoglobin, increased creatine phosphokinase, increased alanine aminotransferase, decreased albumin, decreased lymphocytes, decreased leukocytes, increased aspartate aminotransferase, decreased potassium, and decreased sodium.

Moderate and Strong CYP2C8 Inhibitors: Avoid coadministration with OJEMDA. Moderate and Strong CYP2C8 Inducers: Avoid coadministration with OJEMDA. Certain CYP3A Substrates: Avoid coadministration of OJEMDA with CYP3A substrates where minimal concentration changes can cause reduced efficacy. Hormonal contraceptives: Avoid coadministration with OJEMDA.

Store at 20°C to 25°C (68°F to 77°F), excursions permitted between 15°C to 30°C (59°F to 86°F).