Pemigatinib

PEMAZYRE is a kinase inhibitor indicated: for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma with a fibroblast growth factor receptor 2 (FGFR2) fusion or other rearrangement as detected by an FDA-approved test. This indication is approved under accelerated approval based on overall 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). For the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement.

Pemigatinib is a small molecule kinase inhibitor that targets FGFR1, 2 and 3 with IC 50 values of less than 2 nM. Pemigatinib also inhibited FGFR4 in vitro at a concentration approximately 100 times higher than those that inhibit FGFR1, 2, and 3. Pemigatinib inhibited FGFR1-3 phosphorylation and signaling and decreased cell viability in cancer cell lines with activating FGFR amplifications and fusions that resulted in constitutive activation of FGFR signaling. Constitutive FGFR signaling can support the proliferation and survival of malignant cells.

Cholangiocarcinoma: Confirm the presence of an FGFR2 fusion or rearrangement prior to initiation of treatment with PEMAZYRE. Recommended dosage is 13.5 mg orally once daily for 14 consecutive days followed by 7 days off therapy in 21-day cycles. Continue treatment until disease progression or unacceptable toxicity occurs. Myeloid/lymphoid neoplasms with FGFR1 rearrangement: Recommended dosage is 13.5 mg orally once daily. Continue treatment until disease progression or unacceptable toxicity. All patients treated with PEMAZYRE: Swallow tablet whole, with or without food. Severe Renal Impairment: the recommended dosage of PEMAZYRE is 9 mg with the schedule (intermittent or continuous) designated for the indication. Severe Hepatic Impairment: the recommended dosage of PEMAZYRE is 9 mg with the schedule (intermittent or continuous) designated for the indication.

None. None.

Ocular Toxicity: PEMAZYRE can cause retinal pigment epithelial detachment. Perform ophthalmological examination including optical coherence tomography (OCT) prior to initiation of therapy, every 2 months for the first 6 months of treatment and every 3 months thereafter, and urgently at any time for visual symptoms. Hyperphosphatemia and Soft Tissue Mineralization: PEMAZYRE can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcification, calcinosis, and non-uremic calciphylaxis. Monitor for hyperphosphatemia and withhold, reduce the dose, or permanently discontinue based on duration and severity of hyperphosphatemia. Embryo-Fetal Toxicity: Can cause fetal harm. Advise patients of reproductive potential of the potential risk to the fetus and use effective contraception.

The following adverse reactions are discussed elsewhere in the labeling: Ocular Toxicity Hyperphosphatemia and Soft Tissue Mineralization Cholangiocarcinoma: The most common adverse reactions (incidence ≥ 20%) are hyperphosphatemia, alopecia, diarrhea, nail toxicity, fatigue, dysgeusia, nausea, constipation, stomatitis, dry eye, dry mouth, decreased appetite, vomiting, arthralgia, abdominal pain, hypophosphatemia, back pain, and dry skin. Myeloid/lymphoid neoplasms with FGFR1 rearrangement: The most common (≥ 20%) adverse reactions are hyperphosphatemia, nail toxicity, alopecia, stomatitis, diarrhea, dry eye, fatigue, rash, abdominal pain, anemia, constipation, dry mouth, epistaxis, serous retinal detachment, extremity pain, decreased appetite, dry skin, dyspepsia, back pain, nausea, blurred vision, peripheral edema, and dizziness.

Strong and Moderate CYP3A Inducers: Avoid concomitant use of PEMAZYRE. Strong and Moderate CYP3A Inhibitors: Avoid concomitant use. If concomitant use cannot be avoided, reduce PEMAZYRE dosage.

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