Romvimza Drug Information

ROMVIMZA is indicated for treatment of adult patients with symptomatic tenosynovial giant cell tumor (TGCT) for which surgical resection will potentially cause worsening functional limitation or severe morbidity.

Recommended Dosage

The recommended dosage of ROMVIMZA is 30 mg orally taken twice weekly, with a minimum of 72 hours between doses, as directed on the blister package. Instruct patients to follow the schedule on the blister package and to take ROMVIMZA on the same days each week. ROMVIMZA may be taken with or without food.

Swallow ROMVIMZA capsules whole. Do not open, break, or chew the capsules. If a dose is missed by 48 hours or less, take the missed dose as soon as possible and take the next dose on its regularly scheduled day.

If a dose is missed by more than 48 hours, skip the missed dose, and take the next dose on its regularly scheduled day. If vomiting occurs within 30 minutes of taking a dose, repeat that dose.

Dosage Modifications for Adverse Reactions

The recommended dose reductions for adverse reactions are provided in Table 1. The recommended dosage modifications for hepatotoxicity are summarized in Table 2. Table 2: Recommended Dosage Modifications for Hepatotoxicity

Dosage Modification for P-glycoprotein (P-gp) Substrates

Avoid concomitant use of ROMVIMZA with P-gp substrates. If concomitant use of a P-gp substrate is unavoidable, administer ROMVIMZA at least 4 hours before taking the P-gp substrate unless otherwise recommended in the substrate Prescribing Information.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. The pooled safety population described in the Warnings and Precautions reflects exposure to ROMVIMZA in 83 patients with TGCT enrolled in the double-blind portion and in 35 patients with TGCT in the open-label portion who crossed over to ROMVIMZA in MOTION, and in 135 patients with TGCT or solid tumors in other clinical trials. The safety of ROMVIMZA was evaluated in 83 adult patients with TGCT in MOTION.

MOTION excluded patients with bilirubin, AST, or ALT >ULN. All patients received ROMVIMZA twice weekly until disease progression or unacceptable toxicity. Among these patients, 82% were exposed for 6 months or longer and 30% were exposed for greater than one year.

Serious adverse reactions occurred in 2.4% of patients who received ROMVIMZA. Serious adverse reactions in ≥1% included subcutaneous abscess (1.2%) and cellulitis (1.2%). Permanent discontinuation due to an adverse reaction occurred in 4.8% of patients who received ROMVIMZA.

Adverse reactions leading to permanent discontinuation in one patient each included periorbital edema, neuropathy, rash, and hypertension. Dose reductions due to an adverse reaction or laboratory abnormality occurred in 39% of patients who received ROMVIMZA. Adverse reactions leading to dose reductions in ≥2% of patients receiving ROMVIMZA were rash, periorbital edema, peripheral edema, fatigue, pruritus, face edema, increased CPK, neuropathy, and hypertension.

Dose interruptions due to an adverse reaction or laboratory abnormality occurred in 40% of patients who received ROMVIMZA. The most common (≥20%) adverse reactions, including laboratory abnormalities that occurred in patients receiving ROMVIMZA were increased AST, periorbital edema, fatigue, rash, increased cholesterol, peripheral edema, face edema, decreased neutrophils, decreased leukocytes, pruritus, and increased ALT. Table 3 and Table 4 summarize the adverse reactions and laboratory abnormalities in MOTION during the randomized phase through Week 25.

Effects of ROMVIMZA on Other Drugs Table 5 describes drug interactions where concomitant use with ROMVIMZA affects another drug. Table 5: Effect of ROMVIMZA on Other Drugs P-glycoprotein (P-gp) substrates Prevention or Management Avoid concomitant use with P-gp substrates while taking ROMVIMZA. If concomitant use cannot be avoided, take ROMVIMZA at least 4 hours prior to P-gp substrates unless otherwise recommended in the substrate Prescribing Information.

Mechanism and Clinical Effect(s) This recommendation is based upon a mechanistic understanding of vimseltinib pharmacokinetics and it being a P-gp inhibitor in vitro. Breast Cancer Resistance Protein (BCRP) substrates Prevention or Management Avoid concomitant use with BCRP substrates while taking ROMVIMZA. Organic Cation Transporter 2 (OCT2) substrates Prevention or Management Avoid concomitant use with OCT2 substrates while taking ROMVIMZA.

Pregnancy Risk Summary Based on data from animal studies and its mechanism of action, ROMVIMZA can cause fetal harm when administered to a pregnant woman. There are no available data on vimseltinib use in pregnant women to evaluate for a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. In female rats administered vimseltinib during the period of organogenesis, fetal structural abnormalities occurred at exposures that were at least 3 times the recommended dose based on AUC ( see Data ).

Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is respectively. Structural abnormalities (skeletal variations) occurred at ≥2.5 mg/kg/day (approximately 3 times the exposure at the recommended dose based on AUC). Additional structural abnormalities (cardiac malformations) were observed at the highest dose of 15 mg/kg/day (approximately 23 times the exposure at the recommended dose based on AUC).

Pediatric Use The safety and effectiveness of ROMVIMZA in pediatric patients have not been established. Animal Toxicity Data In a 26-week repeat-dose toxicology study, rats administered vimseltinib at ≥2.5 mg/kg/day had physeal thickening and decay of the incisors and molars. Bone and tooth toxicities occurred at exposures at least 8 times the recommended dose based on AUC.