Narrator: This promotional presentation is being sponsored by Incyte Corporation. The speaker is presenting on behalf of, and is being compensated by, Incyte Corporation.

INDICATIONS AND USAGE

PEMAZYRE (pemigatinib) is 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).

Important Safety Information is discussed later in this video.

Dr Khasawneh: Hello, my name is Dr Mohamad Khasawneh, a practicing hematologist/oncologist. Today I will discuss the management of retinal pigment epithelial detachment associated with PEMAZYRE. Let’s start with a case adapted from a published patient case.

Meet Ms. K. She is a 54-year-old female patient who initially presented with right upper quadrant abdominal pain, weight loss, and jaundice. A computed tomography, or CT, scan revealed multiple intrahepatic metastases, lung metastasis, and mediastinal lymph node metastasis. After a biopsy of the primary lesion, Ms. K was diagnosed with unresectable, metastatic intrahepatic cholangiocarcinoma, or iCCA.

For her first-line treatment, she was initiated on standard-of-care chemotherapy. Comprehensive molecular profiling revealed a fibroblast growth factor receptor 2, or FGFR2, to BICC1 fusion with CDKN2A/B loss.

Ms. K was then prescribed PEMAZYRE as second-line treatment.

PEMAZYRE is an oral FGFR1/2/3 inhibitor that is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma, or CCA, with an FGFR2 fusion or non-fusion rearrangement. It was studied in FIGHT-202, the largest clinical trial to date for an approved second-line treatment for FGFR2 fusion-positive CCA. PEMAZYRE was approved by the FDA based on results from this study.

FIGHT-202 was a Phase 2, multicenter, open-label, single-arm study in previously treated patients with locally advanced or metastatic CCA who had an FGFR2 fusion or non-fusion rearrangement, as determined by a clinical trial assay, FoundationOne® CDx, performed at a central laboratory. Patients received PEMAZYRE in 21-day cycles at a dosage of 13.5 mg orally once daily for 14 days, followed by 7 days off therapy, administered until disease progression or unacceptable toxicity.

The efficacy population consisted of 107 patients with disease that had progressed on or after at least 1 prior therapy. The primary endpoint was overall response rate, or ORR. Secondary endpoints included duration of response, or DoR; disease control rate, or DCR; progression-free survival, or PFS; overall survival, or OS; and safety.

PEMAZYRE received accelerated approval from the FDA based on ORR and DoR.

Among the 107 patients, PEMAZYRE demonstrated an ORR of 36%, with a 95% confidence interval of 27%-45%. 33% of patients achieved a partial response, or PR, and 2.8% achieved a complete response, or CR. The median time to response was 2.7 months, ranging from 0.7-6.9 months.

The median DoR was 9.1 months, with a 95% confidence interval of 6.0-14.5 months. 63% of responders had a DoR of at least 6 months, while 18% of responders had a DoR lasting at least 12 months.

The following additional endpoints are not reflected in the full Prescribing Information. Due to the potential variability in the natural history of the disease, a single-arm study such as FIGHT-202 may not adequately characterize these time-to-event endpoints. For this reason, a confirmatory Phase 3 study in cholangiocarcinoma is underway.

DCR, which was defined as the proportion of patients with a CR, PR, or stable disease (SD), was 82%, with a 95% confidence interval of 74%-89%. CR was seen in 2.8% of patients, PR in 32.7% of patients, and SD in 46.7% of patients. As a reminder, FIGHT-202 was a single-arm study, and in this setting the DCR results may reflect the natural history of CCA in an individual patient rather than the direct effect of the treatment.

The median PFS was 6.9 months, with a 95% confidence interval of 6.2 to 9.6 months. Median follow-up at time of data cutoff was 15.4 months.

The median OS was 21.1 months. The lower bound of the 95% confidence interval was 14.8 months, while the upper bound was not estimable. At the time of data cutoff, median follow-up was 15.4 months, but the OS data were not mature.

Let’s review the safety data from FIGHT-202. The most common adverse reactions in ≥15% of patients were hyperphosphatemia, alopecia, diarrhea, nail toxicity, fatigue, dysgeusia, nausea, constipation, stomatitis, dry eye, dry mouth, decreased appetite, vomiting, arthralgia, abdominal pain, hypophosphatemia, back pain, dry skin, pain in extremity, peripheral edema, headache, weight loss, urinary tract infection, dehydration, and palmar-plantar erythrodysesthesia syndrome.

One potential serious adverse reaction with PEMAZYRE is retinal pigment epithelial detachment, or RPED, which can cause symptoms such as blurred vision, visual floaters, or photopsia. Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, RPED occurred in 11% of patients, including Grade 3-4 RPED in 1.3%. Advise patients to inform you of any vision changes they experience when taking PEMAZYRE.

To monitor for RPED, comprehensive ophthalmological examinations, including optical coherence tomography, or OCT, should be performed prior to initiation of PEMAZYRE therapy. OCT should be repeated every 2 months for the first 6 months of treatment and every 3 months thereafter during treatment.

In the event that RPED occurs, the patient should be urgently referred for ophthalmologic evaluation at the onset of symptoms, with follow-up every 3 weeks until resolution or discontinuation of PEMAZYRE. If the patient is asymptomatic and stable on serial examination, continue treatment with PEMAZYRE. If the patient is symptomatic or worsening on serial examination, withhold PEMAZYRE. Resume PEMAZYRE at a lower dose if the patient is asymptomatic and improved on subsequent examination. However, if symptoms persist or examination does not improve, consider permanently discontinuing PEMAZYRE, based on the patient’s clinical status.

Now, let’s revisit our patient case, Ms. K. On Day 7 of treatment with PEMAZYRE, she experienced bilateral blurred vision and was found to have unifocal Grade 2 RPED.

PEMAZYRE was immediately interrupted for 8 days until her RPED completely resolved.

Ms. K then restarted PEMAZYRE at a reduced dose of 9 mg. When Grade 2 bilateral RPED was confirmed, PEMAZYRE was interrupted for another 9 days. After the re-adhesion of the retinal pigment epithelium, PEMAZYRE was restarted at 4.5 mg.

After Cycle 3, Ms. K’s CT scan showed a 56% reduction in the primary lesion, with disappearance of lung metastasis. As of April 2023, the patient was continuing PEMAZYRE treatment at 4.5 mg, with no new treatment-emergent adverse events.

Careful monitoring and dose modifications are crucial in managing RPED with PEMAZYRE and may allow patients to remain on therapy. For more information, please visit the Managing Adverse Reactions section of this website.

Thank you for joining me here today. Before we conclude, please keep watching to view the Important Safety Information for PEMAZYRE.

Narrator: INDICATIONS AND USAGE

PEMAZYRE is 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).

IMPORTANT SAFETY INFORMATION

Ocular Toxicity

Retinal Pigment Epithelial Detachment (RPED): PEMAZYRE can cause RPED, which may cause symptoms such as blurred vision, visual floaters, or photopsia. Clinical trials of PEMAZYRE did not conduct routine monitoring including optical coherence tomography (OCT) to detect asymptomatic RPED; therefore, the incidence of asymptomatic RPED with PEMAZYRE is unknown.

Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, RPED occurred in 11% of patients, including Grade 3-4 RPED in 1.3%. The median time to first onset of RPED was 56 days. RPED led to dose interruption of PEMAZYRE in 3.1% of patients, and dose reduction and permanent discontinuation in 1.3% and in 0.2% of patients, respectively. RPED resolved or improved to Grade 1 levels in 76% of patients who required dosage modification of PEMAZYRE for RPED.

Perform a comprehensive ophthalmological examination including OCT prior to initiation of PEMAZYRE and every 2 months for the first 6 months and every 3 months thereafter during treatment. For onset of visual symptoms, refer patients for ophthalmologic evaluation urgently, with follow-up every 3 weeks until resolution or discontinuation of PEMAZYRE. Modify the dose or permanently discontinue PEMAZYRE as recommended in the prescribing information for PEMAZYRE.

Dry Eye: Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, dry eye occurred in 31% of patients, including Grade 3-4 in 1.6% of patients. Treat patients with ocular demulcents as needed.

Hyperphosphatemia and Soft Tissue Mineralization

PEMAZYRE can cause hyperphosphatemia leading to soft tissue mineralization, cutaneous calcification, calcinosis, and non-uremic calciphylaxis. Increases in phosphate levels are a pharmacodynamic effect of PEMAZYRE. Among 635 patients who received a starting dose of PEMAZYRE 13.5 mg across clinical trials, hyperphosphatemia was reported in 93% of patients based on laboratory values above the upper limit of normal. The median time to onset of hyperphosphatemia was 8 days (range 1-169). Phosphate lowering therapy was required in 33% of patients receiving PEMAZYRE.

Monitor for hyperphosphatemia and initiate a low phosphate diet when serum phosphate level is >5.5 mg/dL. For serum phosphate levels >7 mg/dL, initiate phosphate lowering therapy and withhold, reduce the dose, or permanently discontinue PEMAZYRE based on duration and severity of hyperphosphatemia as recommended in the prescribing information.

Embryo-Fetal Toxicity

Based on findings in an animal study and its mechanism of action, PEMAZYRE can cause fetal harm when administered to a pregnant woman. Oral administration of pemigatinib to pregnant rats during the period of organogenesis caused fetal malformations, fetal growth retardation, and embryo-fetal death at maternal exposures lower than the human exposure based on area under the curve (AUC) at the clinical dose of 13.5 mg.

Advise pregnant women of the potential risk to the fetus. Advise female patients of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose. Advise males with female partners of reproductive potential to use effective contraception during treatment with PEMAZYRE and for 1 week after the last dose.

Adverse Reactions: Cholangiocarcinoma

Serious adverse reactions occurred in 45% of patients receiving PEMAZYRE (n=146). Serious adverse reactions in ≥2% of patients who received PEMAZYRE included abdominal pain, pyrexia, cholangitis, pleural effusion, acute kidney injury, cholangitis infective, failure to thrive, hypercalcemia, hyponatremia, small intestinal obstruction, and urinary tract infection. Fatal adverse reactions occurred in 4.1% of patients, including failure to thrive, bile duct obstruction, cholangitis, sepsis, and pleural effusion.

Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received PEMAZYRE. Adverse reactions requiring permanent discontinuation in ≥1% of patients included intestinal obstruction and acute kidney injury.

Dosage interruptions due to an adverse reaction occurred in 43% of patients who received PEMAZYRE. Adverse reactions requiring dosage interruption in ≥1% of patients included stomatitis, palmar-plantar erythrodysesthesia syndrome, arthralgia, fatigue, abdominal pain, AST increased, asthenia, pyrexia, ALT increased, cholangitis, small intestinal obstruction, alkaline phosphatase increased, diarrhea, hyperbilirubinemia, electrocardiogram QT prolonged, decreased appetite, dehydration, hypercalcemia, hyperphosphatemia, hypophosphatemia, back pain, pain in extremity, syncope, acute kidney injury, onychomadesis, and hypotension.

Dose reductions due to an adverse reaction occurred in 14% of patients who received PEMAZYRE. Adverse reactions requiring dosage reductions in ≥1% of patients who received PEMAZYRE included stomatitis, arthralgia, palmar-plantar erythrodysesthesia syndrome, asthenia, and onychomadesis.

Clinically relevant adverse reactions occurring in ≤10% of patients included fractures (2.1%). In all patients treated with pemigatinib, 0.5% experienced pathologic fractures (which included patients with and without cholangiocarcinoma [N = 635]). Soft tissue mineralization, including cutaneous calcification, calcinosis, and non-uremic calciphylaxis associated with hyperphosphatemia were observed with PEMAZYRE treatment.

Within the first 21-day cycle of PEMAZYRE dosing, serum creatinine increased (mean increase of 0.2 mg/dL) and reached steady state by Day 8, and then decreased during the 7 days off therapy. Consider alternative markers of renal function if persistent elevations in serum creatinine are observed.

In cholangiocarcinoma (n=146) the most common adverse reactions (incidence ≥20%) were hyperphosphatemia (60%), alopecia (49%), diarrhea (47%), nail toxicity (43%), fatigue (42%), dysgeusia (40%), nausea (40%), constipation (35%), stomatitis (35%), dry eye (35%), dry mouth (34%), decreased appetite (33%), vomiting (27%), arthralgia (25%), abdominal pain (23%), hypophosphatemia (23%), back pain (20%), and dry skin (20%).

Drug Interactions

Avoid concomitant use of strong and moderate CYP3A inhibitors with PEMAZYRE. Reduce the dose of PEMAZYRE if concomitant use with a strong or moderate CYP3A inhibitor cannot be avoided. Avoid concomitant use of strong and moderate CYP3A inducers with PEMAZYRE.

Special Populations

Advise lactating women not to breastfeed during treatment with PEMAZYRE and for 1 week after the last dose.

Reduce the recommended dose of PEMAZYRE for patients with severe renal impairment as described in the prescribing information.

Reduce the recommended dose of PEMAZYRE for patients with severe hepatic impairment as described in the prescribing information.

Please see Full Prescribing Information for PEMAZYRE available on this website.