VIMSELTINIB CAP,ORAL

Clinical Criteria Summary

Known severe allergy to FD&C Yellow No. 5 (tartrazine) and/or No. 6 (Sunset Yellow FCF)
Baseline ALT, AST, total bilirubin above the upper limit of normal
Active liver or biliary tract disease, including nonalcoholic steatohepatitis or cirrhosis
Active or uncontrolled infection
Unmanageable drug interaction
Pregnancy
Lactating

Care provided by a VA / VA Community Care oncologist or locally designated expert
Histologically confirmed diagnosis of symptomatic, nonmetastatic tenosynovial giant cell tumor (TGCT)
TGCT is not amenable to improvement with surgery or surgical resection likely to cause worsening functional limitation or severe morbidity
No improvement after 12 weeks of imatinib; disease progression on imatinib or imatinib is medically inadvisable (i.e. contraindication, unmanageable toxicity, etc.)

For females who can become pregnant: Pregnancy should be excluded prior to receiving vimseltinib
For females who can become pregnant and males with partners who can become pregnant: Counseling provided on potential risks vs benefits of treatment and the use of effective contraception during therapy and for 1 month after stopping treatment
For females who are lactating / providing breastmilk to an infant: Advise not to breastfeed during therapy and for 1 month after stopping treatment

Adults with symptomatic tenosynovial giant cell tumor (TGCT)
Disease for which surgical resection will potentially cause worsening functional limitation or severe morbidity
Histologically confirmed TGCT
≥ 1 lesion measuring ≥ 2 cm in size

30 mg orally twice weekly, with a minimum of 72 hours between doses, on the same days each week
Modify dosage for adverse reactions including hepatotoxicity
Avoid concomitant use with P-glycoprotein (P-gp) substrates if possible; otherwise administer vimseltinib at least 4 hours before P-gp substrates
Avoid BCRP and OCT2 substrates

Assess liver tests, including AST, ALT, total bilirubin, direct bilirubin, ALP, and GGT
Verify pregnancy status in women of reproductive potential
Advise pregnant women on the potential risk to the fetus
Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment and for 1 month after the last dose
Advise lactating women not to breastfeed/provide breastmilk to infants

Liver tests twice a month for the first 2 months and once every 3 months for the first year, then as clinically indicated
Monitor renal function using measures other than serum creatinine due to drug-lab interaction
Note: Increased serum creatinine may occur without affecting actual renal function

No boxed warnings or contraindications
Hepatotoxicity warning; modify dosage for adverse reactions including hepatotoxicity
Embryofetal toxicity warning; can cause fetal harm with animal studies showing fetal structural abnormalities including skeletal variations and cardiac malformations
Allergic reactions to FD&C Yellow No. 5 (tartrazine) and No. 6 (Sunset Yellow FCF); tartrazine sensitivity often seen in patients with aspirin sensitivity
Mild hepatic impairment: No dosage adjustment recommended
Moderate or severe hepatic impairment: Not studied

NCCN Guidelines: Preferred regimen (Category 1) for symptomatic TGCT associated with severe morbidity or functional limitations not amenable to surgical improvement
May be used in patients with inadequate response, intolerance, or medical inadvisability to imatinib