Narrator: This promotional presentation is being sponsored by lncyte Corporation. The speaker is presenting on behalf of, and is being compensated by, lncyte 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 be discussing comprehensive molecular profiling and how it can inform your treatment decisions in intrahepatic cholangiocarcinoma, or iCCA.

Given the emerging evidence regarding actionable targets for treating biliary tract cancers, or BTCs, the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) recommend comprehensive molecular testing for patients with unresectable or metastatic cholangiocarcinoma, or CCA, who are candidates for systemic therapy. The test results could inform treatment decisions, so testing should be performed at diagnosis of unresectable or metastatic iCCA.

Let's review a patient case. Meet Mr. B. He is a 59-year-old male patient who initially presented with right upper quadrant abdominal pain, weight loss, and jaundice. Upon initial evaluation, Mr. B was diagnosed with iCCA before liver and mediastinal lymph node biopsies confirmed the disease was de novo, unresectable, and metastatic. At iCCA diagnosis, patients like Mr. B should be tested for actionable genomic alterations with comprehensive molecular testing.

Molecular profiling and targeted therapy are transforming patient care in iCCA. Approximately 50% of patients with CCA have actionable genomic alterations, with fibroblast growth factor receptor 2, or FGFR2, fusions being among the most common, occurring in 10%-16% of patients. Testing for actionable genetic alterations such as FGFR2 fusions can help you make the most appropriate treatment decisions for your patients.

Choosing the right assay is important. In patients with CCA, FGFR2 fusions may have a wide variety of fusion partners, both known, meaning frequently occurring, as well as unknown, meaning rare or patient specific fusions, including those unique to a single patient.

In order to provide the most valuable information, an assay should meet two criteria: first, it should specifically detect FGFR2 fusions, which are distinct from FGFR2 mutations. Second, it should detect fusions with a wide range of known or unknown fusion partners. Molecular profiling using next-generation sequencing, or NGS, allows for simultaneous detection of multiple genomic alterations from a single sample. Note, however, that not all NGS-based tests meet these criteria. For PEMAZYRE, the Foundation One® CDx is the companion diagnostic device approved by the FDA.

Let's discuss biopsy technique. It can be challenging to obtain sufficient tissue for molecular profiling in iCCA tumors. Although it is more invasive, the core-needle biopsy technique can acquire sufficient tissue yield for comprehensive molecular profiling.

Now back to Mr. B. Molecular profiling with NGS that was done at diagnosis found that his tumors harbored an FGFR2 fusion. This meant that Mr. B would be an ideal candidate for a targeted therapy that inhibits FGFR2, such as PEMAZYRE, in the second line if his disease progressed.

Mr. B received gemcitabine and oxaliplatin as first-line therapy. At 9 months of follow-up, it was found that his iCCA was progressing, so his treatment was discontinued.

Since NGS showed Mr. B's iCCA was FGFR2 fusion positive, he was initiated on PEMAZYRE as second-line therapy. After 10 weeks on PEMAZYRE, Mr. B achieved a partial response, as assessed via positron-emission tomography/computed tomography. At 12 months, subsequent scans showed Mr. B's iCCA to be stable.

At his 6-month follow-up, Mr. B experienced an onset of asymptomatic retinal pigment epithelial detachment, or RPED, but it remained stable upon subsequent examinations. He also experienced mild hyperphosphatemia. which was managed through low-phosphate diet counseling and sevelamer. As of November 2022, Mr. B's treatment with PEMAZYRE was ongoing.

PEMAZYRE is an oral FGFR1/2/3 inhibitor that is indicated for the treatment of adults with previously treated, unresectable locally advanced or metastatic CCA with an FGFR2 fusion or non—fusion arrangement. 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 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, 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 of at least 12 months.

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.

PEMAZYRE now has over 4 years of clinical experience since FDA approval. Over 1,500 patients have been treated with PEMAZYRE.

Early molecular profiling with the right test and biopsy technique can help identify FGFR2 fusions to inform treatment in iCCA. Find out if your patient with iCCA is eligible for PEMAZYRE.

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

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.