Pemigatinib (Pemazyre®): A Comprehensive Oncological Drug Monograph

Executive Summary

Pemigatinib (Pemazyre®) represents a significant milestone in precision oncology, establishing itself as a foundational targeted therapy for malignancies driven by fibroblast growth factor receptor (FGFR) aberrations. This small-molecule kinase inhibitor demonstrates potent and selective activity against FGFR1, 2, and 3, addressing a critical unmet need in specific patient populations. Its initial accelerated approval by the U.S. Food and Drug Administration (FDA) for adults with previously treated, unresectable locally advanced or metastatic cholangiocarcinoma (CCA) harboring an FGFR2 fusion or other rearrangement was based on the compelling efficacy data from the Phase II FIGHT-202 trial. This study demonstrated a clinically meaningful objective response rate of 37% and a median duration of response of 9.1 months in a patient population with limited therapeutic options.

Subsequently, pemigatinib secured a second indication for adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with an FGFR1 rearrangement, based on the high rates of complete response observed in the Phase II FIGHT-203 study. This dual approval underscores the drug's efficacy across different tumor types when a clear, targetable oncogenic driver is present. The clinical application of pemigatinib is inextricably linked to companion diagnostics, with the FoundationOne CDx test being essential for identifying the requisite FGFR alterations, thereby embedding genomic profiling into the standard of care for these diseases.

The safety profile of pemigatinib is well-characterized and considered manageable, though it requires proactive monitoring and multidisciplinary management. The most common and clinically significant adverse events are on-target effects, including hyperphosphatemia and ocular toxicities such as serous retinal detachment. Established guidelines for monitoring and dose modification are critical for optimizing treatment tolerability and duration.

Despite its efficacy, acquired resistance inevitably emerges, primarily through on-target secondary mutations in the FGFR2 kinase domain (e.g., gatekeeper and molecular brake mutations) or activation of bypass signaling pathways. The characterization of these resistance mechanisms provides a clear rationale for the development of next-generation FGFR inhibitors and biomarker-driven therapeutic sequencing. Ongoing research, including the pivotal Phase III FIGHT-302 confirmatory trial in first-line CCA and studies exploring combinations with immunotherapy, aims to expand pemigatinib's role and enhance its clinical benefit. Real-world evidence has largely corroborated the findings of the pivotal trials, further solidifying pemigatinib's position as a vital therapeutic agent in the armamentarium against FGFR-driven cancers.

Introduction to Pemigatinib and its Target: The FGFR Pathway

The landscape of cancer treatment has been profoundly reshaped by the advent of precision medicine, which seeks to target the specific molecular drivers of a patient's malignancy. Pemigatinib (Pemazyre®) stands as a prime example of this paradigm, offering a targeted therapeutic approach for cancers defined by specific genetic alterations in the fibroblast growth factor receptor (FGFR) pathway.

The Fibroblast Growth Factor Receptor (FGFR) Pathway in Oncology

The FGFR signaling pathway is a crucial regulator of a multitude of normal cellular functions, including cell proliferation, differentiation, survival, migration, and angiogenesis.[1] This pathway consists of four highly conserved transmembrane receptor tyrosine kinases (FGFR1, FGFR2, FGFR3, and FGFR4) and their corresponding fibroblast growth factor (FGF) ligands. In normal physiological states, the binding of an FGF ligand to its receptor induces receptor dimerization and autophosphorylation of tyrosine residues in the intracellular kinase domain. This event initiates a cascade of downstream signaling, primarily through the RAS/mitogen-activated protein kinase (MAPK) and the phosphatidylinositol 3-kinase (PI3K)/AKT pathways, which ultimately govern cellular behavior.[1]

In oncology, this tightly regulated system can become hijacked. Aberrant, constitutive (ligand-independent) activation of the FGFR pathway, driven by genetic alterations such as gene fusions, rearrangements, amplifications, and activating mutations, has been identified as a key oncogenic driver in a wide variety of human cancers. These cancers include those of the urinary bladder, breast, endometrium, lung, stomach, and, most notably for pemigatinib, the biliary tract.[1] This deregulated signaling promotes uncontrolled cancer cell proliferation, enhances tumor angiogenesis, and allows for the evasion of apoptosis, making the FGFR pathway a compelling target for therapeutic intervention.[1]

FGFR Alterations as Actionable Targets in Cholangiocarcinoma and Myeloid/Lymphoid Neoplasms

Cholangiocarcinoma (CCA) is a rare and aggressive malignancy of the biliary tract with a historically poor prognosis, accounting for 15% to 20% of primary hepatobiliary malignancies.[3] The discovery that a distinct molecular subtype of intrahepatic CCA (iCCA) is driven by alterations in the

FGFR2 gene has been a pivotal breakthrough. Approximately 10% to 16% of patients with iCCA harbor FGFR2 gene fusions or other rearrangements, which result in the expression of constitutively active oncogenic fusion proteins.[3] This finding established

FGFR2 as a bona fide actionable target in this disease.

Similarly, a subset of rare and aggressive hematologic cancers, classified as myeloid/lymphoid neoplasms (MLNs), are defined by the presence of rearrangements involving the FGFR1 gene. These FGFR1 rearrangements lead to the formation of fusion proteins with constitutive kinase activity, driving the pathogenesis of these aggressive neoplasms.[10]

Pemigatinib (Pemazyre®): A Novel Therapeutic Solution

Pemigatinib was developed as a potent, selective, orally bioavailable small-molecule inhibitor of the kinase activity of FGFR1, FGFR2, and FGFR3.[1] By targeting the specific molecular aberration driving the cancer, pemigatinib exemplifies the principles of precision medicine. Its development and subsequent approval provided the first targeted therapy for patients with

FGFR2-rearranged CCA and a much-needed effective option for patients with FGFR1-rearranged MLNs, fundamentally changing the treatment algorithm for these molecularly defined patient populations.

Table 1: Key Drug Characteristics of Pemigatinib

Characteristic	Detail
Brand Name	Pemazyre®
Generic Name	Pemigatinib
DrugBank ID	DB15102
CAS Number	1513857-77-6
Type	Small Molecule
ATC Code	L01EN02
Molecular Formula	C24​H27​F2​N5​O4​
Molecular Weight	487.5 g/mol

Data sourced from.[1]

Molecular Pharmacology

The therapeutic utility of pemigatinib is rooted in its specific molecular interactions with the FGFR family and its resulting pharmacokinetic and pharmacodynamic properties.

Mechanism of Action

Pemigatinib functions as a small-molecule kinase inhibitor that is both potent and selective for FGFR isoforms 1, 2, and 3.[5] It acts as an ATP-competitive inhibitor, binding to the ATP-binding pocket within the intracellular kinase domain of these receptors.[2] This binding action physically obstructs the phosphorylation of the receptor, thereby preventing its autophosphorylation and subsequent activation. By blocking this critical initial step, pemigatinib effectively halts the downstream signaling cascades that are constitutively activated by oncogenic

FGFR alterations. These inhibited pathways include the RAS/MAPK and PI3K/AKT signaling axes, which are fundamental for tumor cell growth, proliferation, and survival.[1]

The potency of pemigatinib is underscored by its half-maximal inhibitory concentration (IC50​) values, which are less than 2 nM for FGFR1, FGFR2, and FGFR3. In contrast, its activity against FGFR4 is approximately 100-fold weaker, highlighting its selectivity within the FGFR family.[1] This potent and selective inhibition of aberrant FGFR signaling is the core mechanism through which pemigatinib exerts its antitumor activity.

Pharmacodynamics

The pharmacodynamic effects of pemigatinib are directly linked to its mechanism of action. The most prominent on-target effect is hyperphosphatemia, an elevation of serum phosphate levels.[16] This is a well-recognized class effect of FGFR inhibitors. It occurs because the FGFR pathway, specifically through the ligand FGF23, plays a key role in phosphate homeostasis by regulating its excretion in the kidneys. By inhibiting FGFR signaling, pemigatinib blocks the action of FGF23, leading to increased renal phosphate reabsorption and consequently higher serum phosphate levels.[19] While hyperphosphatemia is an adverse event that requires clinical management, its presence also serves as a de facto biomarker of target engagement, providing tangible, early evidence that the drug is effectively inhibiting its intended target.

Another documented pharmacodynamic effect is a potential increase in serum creatinine. This is understood to be a result of pemigatinib decreasing the renal tubular secretion of creatinine, rather than indicating true glomerular filtration impairment.[16]

Pharmacokinetics (ADME)

The clinical utility of pemigatinib is supported by a favorable pharmacokinetic profile.

• Absorption: Following a single oral dose of 13.5 mg, pemigatinib is rapidly absorbed, with the median time to reach maximum plasma concentration (Tmax​) being 1.13 hours. Administration with or without food is permissible, as a high-fat, high-calorie meal does not produce a clinically significant effect on the drug's concentration.[1]
• Distribution: Information regarding protein binding and volume of distribution was not detailed in the provided materials.
• Metabolism: While the specific metabolic pathways and resultant metabolites have not been fully characterized, the potential for drug-drug interactions mediated by the cytochrome P450 system, particularly CYP3A4, has been identified. Concomitant use with strong or moderate inhibitors or inducers of CYP3A4 can alter pemigatinib exposure, necessitating dose adjustments or avoidance.[1]
• Excretion: The primary route of elimination is through the feces. Following a single radiolabeled oral dose, approximately 82.4% of the administered dose was recovered in the feces, with a smaller portion recovered in urine.[1]
• Steady State: With once-daily dosing, pemigatinib reaches steady-state plasma concentrations within 4 days. The median drug accumulation ratio is 1.63, and steady-state concentrations have been shown to increase in a dose-proportional manner across a range of 1 mg to 20 mg.[1] At the recommended dose, the mean steady-state area under the curve (AUC) and maximum concentration ( Cmax​) were 2620 nM·h and 236 nM, respectively.[1]

Clinical Efficacy in Approved Indications

The regulatory approvals for pemigatinib are founded on robust efficacy data from two pivotal Phase II trials, FIGHT-202 for cholangiocarcinoma and FIGHT-203 for myeloid/lymphoid neoplasms.

A. Metastatic Cholangiocarcinoma (Second-Line and Beyond)

Pivotal Trial - FIGHT-202 (NCT02924376)

The FIGHT-202 study was a multicenter, open-label, single-arm Phase II trial that served as the primary basis for pemigatinib's approval in CCA.[4]

• Study Design and Patient Population: The trial enrolled 146 patients with advanced or metastatic CCA who had progressed on at least one prior line of therapy. The key efficacy cohort (Cohort A) consisted of 107 patients whose tumors were confirmed to harbor an FGFR2 gene fusion or rearrangement, as identified by a central laboratory assay.[22] Patients received pemigatinib at a dose of 13.5 mg orally once daily for 14 days, followed by a 7-day rest period, in 21-day cycles.[22]
• Efficacy Results (Final Analysis): The final, mature results of the FIGHT-202 trial were presented at the ESMO World Congress on Gastrointestinal Cancer in 2022, after a median follow-up of 45.4 months.[24] These results confirmed the initial promising data and solidified the drug's efficacy profile.
• Overall Response Rate (ORR): The primary endpoint was the ORR in Cohort A, which was 37.0% as assessed by an independent review committee. The disease control rate (DCR), which includes complete responses, partial responses, and stable disease, was 82.4%.[24]
• Duration of Response (DOR): The median DOR, a key secondary endpoint, was 9.1 months, indicating that the responses achieved were durable.[24]
• Progression-Free and Overall Survival (PFS/OS): In this heavily pre-treated population, pemigatinib demonstrated a median PFS of 7.0 months and a median OS of 17.5 months.[24] An earlier post-hoc analysis had shown that the median OS was significantly prolonged in patients who responded to therapy (30.1 months) compared to non-responders (13.7 months).[25]
• Clinical Significance: In the context of second-line metastatic CCA, where historical outcomes with chemotherapy are poor, these efficacy results were considered highly clinically meaningful. At the time of its approval, there were no other targeted therapies available for this patient population, making pemigatinib a practice-changing agent.[4]

B. Relapsed/Refractory Myeloid/Lymphoid Neoplasms (MLNs)

Pivotal Trial - FIGHT-203 (NCT03011372)

The approval of pemigatinib for MLNs was based on the FIGHT-203 trial, a Phase II, open-label, single-arm study evaluating its efficacy in patients with these rare and aggressive hematologic malignancies driven by FGFR1 rearrangements.[10]

• Study Design and Patient Population: The trial enrolled patients with relapsed or refractory MLNs with a documented FGFR1 rearrangement who had either relapsed after or were ineligible for allogeneic hematopoietic stem cell transplantation (allo-HSCT) or other disease-modifying therapies.[11]
• Efficacy Results: The trial demonstrated remarkably high and durable response rates.
• Complete Response (CR): Among 28 evaluable patients with relapsed or refractory disease, the CR rate was 78% (18 of 28 patients) in those with chronic phase disease in the bone marrow with or without extramedullary disease.[29] Among 31 patients with chronic phase disease only, the investigator-assessed CR rate was 83.3% (15 of 18 patients).[11]
• Cytogenetic Response: The complete cytogenetic response (CCyR) rate, a measure of the eradication of the chromosomal abnormality, was 75.8% as assessed by a central review committee.[11]
• Clinical Significance: The profound efficacy, particularly the high rates of complete hematologic and cytogenetic responses, in this rare and often fatal disease underscored the potent activity of pemigatinib when a clear oncogenic driver like an FGFR1 rearrangement is present. These results led to the FDA's approval, providing a critical new targeted therapy for this patient population.[10]

Table 2: Summary of Efficacy from Pivotal Trials (FIGHT-202 & FIGHT-203)

Indication	Trial	Patient Population	N	Primary Endpoint	ORR (CR/PR %)	DCR (%)	Median DOR (months)	Median PFS (months)	Median OS (months)
Cholangiocarcinoma	FIGHT-202	≥2L, FGFR2 fusion/rearrangement	107	ORR	37.0% (2.8%/34.3%)	82.4%	9.1	7.0	17.5
Myeloid/Lymphoid Neoplasms	FIGHT-203	R/R, FGFR1 rearrangement	28	CR Rate	78% (CR)	N/A	Not Reached	N/A	N/A

Data sourced from.[4] N/A = Not Applicable/Not Reported as primary or key secondary endpoint in these sources. R/R = Relapsed/Refractory. ≥2L = Second-line or greater therapy.

Safety Profile and Management of Adverse Events

The safety profile of pemigatinib has been well-characterized across its clinical development program. While generally considered manageable, it is associated with a distinct set of on-target adverse events that require proactive monitoring and a structured management approach to ensure patient safety and optimize treatment duration.

Comprehensive Safety Profile

The safety of pemigatinib has been evaluated in a pooled population of 635 patients across clinical trials.[30] The most frequently reported adverse drug reactions (ADRs) are directly related to its mechanism of action as an FGFR inhibitor. These common ADRs (incidence ≥20%) include hyperphosphatemia, alopecia (hair loss), diarrhea, nail toxicity, fatigue, dysgeusia (taste alteration), nausea, constipation, stomatitis (mouth sores), dry eye, dry mouth, decreased appetite, vomiting, arthralgia (joint pain), abdominal pain, hypophosphatemia, back pain, and dry skin.[16]

In the pivotal FIGHT-202 safety population (n=146), serious adverse events (SAEs) occurred in 45% of patients. The most common SAEs (≥2%) included abdominal pain, pyrexia, cholangitis, and pleural effusion. Fatal adverse events occurred in 4.1% of patients, though none were deemed by investigators to be related to pemigatinib treatment.[27]

The tolerability profile is reflected in the rates of dose modifications. Permanent discontinuation due to an adverse reaction occurred in 9% of patients. Dose reductions were required in 14% of patients, and dose interruptions were necessary in a larger proportion, with specific toxicities like stomatitis, arthralgia, and palmar-plantar erythrodysesthesia syndrome being common triggers.[27]

Table 3: Common and Serious Adverse Events (AEs) with Pemigatinib (FIGHT-202, N=146)

System Organ Class	Adverse Event	Frequency (All Grades, %)	Frequency (Grade ≥3, %)
Metabolism and Nutrition	Hyperphosphatemia	60	0
	Hypophosphatemia	23	12
	Decreased appetite	33	1.4
Skin and Subcutaneous Tissue	Alopecia	49	0
	Nail toxicity	43	2.1
	Dry skin	20	0.7
	Palmar-plantar erythrodysesthesia	15	4.1
Gastrointestinal	Diarrhea	47	2.7
	Nausea	40	2.1
	Stomatitis	35	5
	Constipation	35	0.7
	Dry mouth	34	0
General Disorders	Fatigue	42	4.8
Eye Disorders	Dry eye	35	0.7
	Serous retinal detachment	11 (in N=635)	1.3 (in N=635)
Musculoskeletal	Arthralgia	25	6

Data sourced from.[16] Frequencies are from the FIGHT-202 safety population unless otherwise noted.

Detailed Management Protocols for Key Toxicities

Successful administration of pemigatinib hinges on the diligent management of its characteristic, on-target toxicities.

Ocular Toxicity (RPED and Dry Eye)

Pemigatinib can cause serous retinal detachment (RPED), which may present with symptoms such as blurred vision, visual floaters, or photopsia.[16] Dry eye is also a common occurrence.

• Monitoring: A rigorous monitoring schedule is mandated. This includes a comprehensive ophthalmological examination with optical coherence tomography (OCT) prior to starting therapy, every 2 months for the first 6 months, and every 3 months thereafter. Any new visual symptoms should trigger an urgent ophthalmologic referral.[17]
• Management: Prophylactic use of ocular demulcents (artificial tears) is recommended to prevent or treat dry eye.[16] For RPED, management is guided by symptoms and OCT findings. Asymptomatic and stable RPED may not require treatment interruption. However, for symptomatic or worsening RPED, pemigatinib should be withheld. If the condition resolves or improves, treatment can be resumed at a reduced dose. If it persists, permanent discontinuation should be considered.[18]

Hyperphosphatemia and Soft Tissue Mineralization

As a direct pharmacodynamic effect, hyperphosphatemia is nearly universal but typically low-grade and manageable.

• Monitoring: Serum phosphate levels must be monitored regularly throughout treatment.[17]
• Management: A tiered management strategy is recommended:

1. For serum phosphate levels >5.5 mg/dL, a phosphate-restricted diet should be initiated.
2. For levels >7 mg/dL, phosphate-lowering therapy (e.g., phosphate binders) should be started.
3. For persistent or severe hyperphosphatemia (>10 mg/dL), pemigatinib should be withheld. Treatment can be resumed at the same or a reduced dose once levels are controlled. Recurrent severe hyperphosphatemia after dose reductions may necessitate permanent discontinuation.[16]

Dermatologic and Mucosal Toxicities

• Nail Toxicity: This can manifest as onycholysis, paronychia, or nail dystrophy. Management is primarily preventative and supportive, including avoiding nail trauma, using emollients, and wearing loose-fitting footwear.[16]
• Stomatitis: Good oral hygiene is crucial. Management may include avoidance of irritating foods and use of supportive care agents like coating agents or non-alcohol-based mouthwashes.[16]
• Alopecia: This is a common but low-grade event. Management is supportive, focusing on patient counseling and cosmetic solutions like camouflaging methods.[16]

Table 4: Recommended Management and Dose Modification for Key Toxicities

Toxicity	Severity / Level	Monitoring	Management Action
Serous Retinal Detachment (RPED)	Asymptomatic & Stable	OCT every 2-3 months	Continue pemigatinib at current dose.
	Symptomatic or Worsening	Urgent ophthalmologic exam, then every 3 weeks	Withhold pemigatinib. If resolves/improves, resume at a reduced dose. If persists, consider discontinuation.
Hyperphosphatemia	Serum Phosphate >5.5 mg/dL	Weekly serum phosphate	Initiate low-phosphate diet.
	Serum Phosphate >7.0 mg/dL	Weekly serum phosphate	Initiate phosphate-lowering therapy. If levels do not improve to <7 mg/dL within 2 weeks, withhold pemigatinib. Resume at same dose upon improvement. For recurrence, resume at a reduced dose.
	Serum Phosphate >10 mg/dL	Weekly serum phosphate	Initiate phosphate-lowering therapy. Withhold pemigatinib if levels persist >10 mg/dL for 1 week. Resume at a reduced dose when <7 mg/dL. Permanently discontinue for recurrence after 2 dose reductions.

Data sourced from.[18]

Dosing, Administration, and Regulatory Status

The effective and safe use of pemigatinib requires adherence to specific dosing schedules tailored to the indication, awareness of potential drug interactions, and an understanding of its global regulatory status and the integral role of companion diagnostics.

Dosage and Administration

The recommended dosing for pemigatinib differs based on the approved indication:

• Cholangiocarcinoma: The standard dose is 13.5 mg administered orally once daily for 14 consecutive days, followed by a 7-day drug-free period. This constitutes a 21-day treatment cycle.[21]
• Myeloid/Lymphoid Neoplasms: For this hematologic indication, the recommended dose is 13.5 mg orally once daily on a continuous basis, without a drug-free interval.[35]

Pemigatinib tablets should be swallowed whole and can be taken with or without food at approximately the same time each day. If a dose is missed by 4 or more hours, or if vomiting occurs, the patient should skip that dose and resume with the next scheduled dose.[21]

For management of toxicities, a tiered dose reduction schedule is in place, with the dose being reduced from 13.5 mg to 9 mg, and then to 4.5 mg as needed. If a patient cannot tolerate the 4.5 mg dose, treatment should be permanently discontinued.[21]

A critical aspect of administration is managing potential drug-drug interactions. Pemigatinib is metabolized by the cytochrome P450 3A4 (CYP3A4) enzyme. Therefore, concomitant use with strong or moderate CYP3A4 inhibitors (which can increase pemigatinib exposure and toxicity) should be avoided. If unavoidable, the pemigatinib dose must be reduced. Conversely, co-administration with strong or moderate CYP3A4 inducers (which can decrease pemigatinib exposure and efficacy) should be avoided entirely.[1]

Global Regulatory Landscape

Pemigatinib has achieved regulatory approval in major markets worldwide, though with some notable regional differences.

• FDA (United States): Granted accelerated approval for second-line CCA with an FGFR2 fusion or rearrangement on April 17, 2020.[4] A subsequent approval for relapsed or refractory MLNs with an FGFR1 rearrangement was granted on August 26, 2022.[10]
• EMA (Europe): Received conditional marketing authorisation for the CCA indication in March 2021.[37] However, on March 27, 2025, the EMA's Committee for Medicinal Products for Human Use (CHMP) recommended the refusal of a variation to extend the indication to MLNs. The refusal was based on the conclusion that the single-arm data from the FIGHT-203 trial was not sufficiently comprehensive and that the company was unable to commit to a requested registry-based study to generate further data.[37]
• Health Canada: Issued a Notice of Compliance with Conditions for the CCA indication on September 17, 2021.[28]
• Other Regions: Pemigatinib has also been approved for the CCA indication in other major jurisdictions, including Japan (PMDA) and China (NMPA).[42]

The divergence in regulatory decisions for the MLN indication between the FDA and EMA is noteworthy. It reflects differing regulatory philosophies regarding the evidence required for rare diseases with high unmet need. The FDA's accelerated approval pathway appeared to place greater weight on the strength of the efficacy signal (high CR rate) from a single-arm trial in a rare disease context. In contrast, the EMA placed a stronger emphasis on the need for more comprehensive data and robust post-marketing commitments, even for a conditional authorisation, which the applicant was unable to fulfill.[10] This highlights a key challenge in global drug development and commercialization strategies for orphan indications.

Companion Diagnostics

The use of pemigatinib is a prime example of biomarker-driven therapy. Its efficacy is confined to patients whose tumors harbor specific FGFR alterations. Therefore, the identification of eligible patients through a validated genomic test is a mandatory prerequisite for treatment.

The FDA concurrently approved Foundation Medicine's FoundationOne CDx as the companion diagnostic for pemigatinib.[1] This next-generation sequencing (NGS)-based test is designed to detect a wide range of genomic alterations, including the

FGFR2 fusions and rearrangements required for the CCA indication.[5] The integration of this companion diagnostic into the approval process underscores the inseparable link between advanced genomic profiling and the delivery of modern targeted cancer therapies.

Mechanisms of Therapeutic Resistance

While pemigatinib can induce durable responses, the eventual development of therapeutic resistance is a significant clinical challenge. Understanding the mechanisms of both primary (innate) and acquired resistance is crucial for optimizing patient selection and developing next-generation treatment strategies.

Primary Resistance

Primary resistance refers to the lack of an initial response to pemigatinib in patients whose tumors harbor the target FGFR alteration. Data from the exploratory Phase II FIGHT-207 basket study provide important clues into these mechanisms. The study found that the presence of baseline co-mutations in key tumor suppressor genes, particularly TP53 and ARID1A, was associated with a lack of response and shorter progression-free survival in patients treated with pemigatinib.[6] Similarly, co-occurring oncogenic alterations in the downstream MAPK signaling pathway were also linked to primary resistance. This suggests that in some tumors, even with an

FGFR driver, parallel oncogenic pathways can provide an escape route from the effects of FGFR inhibition from the outset.

Interestingly, the same study identified that baseline alterations in the tumor suppressor gene BAP1 were positively correlated with both clinical benefit and response to pemigatinib, suggesting that BAP1 status could potentially serve as a positive predictive biomarker for patient selection.[6]

Acquired Resistance

Acquired resistance occurs in tumors that initially respond to pemigatinib but subsequently progress. The primary mechanism underlying this phenomenon is the emergence of new mutations that circumvent the drug's inhibitory action. Serial analysis of circulating tumor DNA (ctDNA) from patients at the time of progression has been instrumental in elucidating these mechanisms.[6]

• On-Target Kinase Domain Mutations: The most common mechanism of acquired resistance is the development of secondary mutations within the kinase domain of the FGFR2 gene itself. These mutations prevent pemigatinib from effectively binding to and inhibiting the receptor. Two key mutational hotspots have been identified [6]:
• Gatekeeper Mutations: Occurring at residue V565 (e.g., V565F, V565I, V565L), these mutations are located at the "gatekeeper" position that controls access of the inhibitor to a hydrophobic pocket within the ATP-binding site. Altering this residue sterically hinders the binding of reversible inhibitors like pemigatinib.
• Molecular Brake Mutations: Occurring at residue N550 (e.g., N550H, N550K), these mutations affect the "molecular brake" region, a hydrogen bond network that helps to constrain the kinase in its inactive conformation. Mutations here can lead to a conformation that is resistant to inhibition.
• Bypass Pathway Activation: A secondary mechanism of resistance involves the tumor acquiring new mutations in other signaling pathways, effectively creating a "bypass" route for growth signals. Emergent mutations in genes such as PIK3CA and members of the RAS family (KRAS, NRAS, HRAS) have been identified in patients progressing on pemigatinib, allowing the tumor to sustain proliferation despite continued FGFR blockade.[6]

The detailed characterization of these acquired resistance mutations is not merely an academic exercise; it provides a clear and actionable roadmap for the future of FGFR-targeted therapy. Knowledge of specific resistance mutations, such as those at the gatekeeper residue, directly informs the rational design of next-generation FGFR inhibitors, such as irreversible (covalent) inhibitors, that are engineered to overcome these specific alterations. This understanding also establishes a strong clinical rationale for performing re-biopsy (either tissue or liquid via ctDNA) at the time of disease progression. By identifying the specific mechanism of resistance, clinicians may be able to guide the selection of a subsequent therapy, creating a dynamic, biomarker-driven treatment sequence that extends the benefit of targeted therapy beyond a single line.

Comparative Landscape and Future Directions

Pemigatinib entered the clinical arena as a first-in-class agent, but the therapeutic landscape for FGFR-altered cancers is evolving. Its position is defined by comparisons with other FGFR inhibitors, the outcomes of ongoing confirmatory trials, and the potential for combination therapies.

Comparative Analysis with Other FGFR Inhibitors

The main comparators for pemigatinib in CCA are futibatinib (Lytgobi) and infigratinib (Truseltiq). As no head-to-head trials have been conducted, comparisons rely on data from single-arm studies and indirect treatment comparisons.

• Mechanism: A key differentiator is the mechanism of binding. Pemigatinib and infigratinib are reversible, ATP-competitive inhibitors. In contrast, futibatinib is an irreversible (covalent) inhibitor, which forms a covalent bond with a cysteine residue in the FGFR kinase domain. This irreversible binding may confer an advantage against certain acquired resistance mutations.[50]
• Efficacy: Unanchored matching-adjusted indirect comparisons (MAICs) have been conducted between futibatinib (from the FOENIX-CCA2 trial) and pemigatinib (from the FIGHT-202 trial). These analyses have shown no statistically significant differences in efficacy outcomes, including ORR, DOR, PFS, and OS. However, consistent numerical trends favoring futibatinib have been reported across all efficacy parameters.[50] For example, one analysis reported an adjusted hazard ratio for OS of 0.83 (95% CI, 0.51-1.36) for futibatinib versus pemigatinib, indicating a non-significant trend toward better survival with futibatinib.[51] In cross-trial comparisons, infigratinib has demonstrated a lower ORR (23%) and shorter median DOR (5 months) compared to pemigatinib (36% ORR, 9.1 months DOR), suggesting potentially lower efficacy.[53]
• Dosing and Safety: Dosing schedules differ, with pemigatinib administered on a 14-days-on, 7-days-off cycle, while infigratinib is given on a 21-days-on, 7-days-off cycle.[55] Safety profiles are broadly similar, dominated by on-target class effects like hyperphosphatemia and ocular toxicity, though subtle differences may exist that could influence clinical decision-making for individual patients.

Ongoing and Future Research

The future role of pemigatinib will be shaped by several ongoing research efforts.

• FIGHT-302 (NCT03656536): This is the pivotal Phase III confirmatory trial for pemigatinib. It is a randomized, open-label study comparing pemigatinib monotherapy against the standard-of-care chemotherapy combination of gemcitabine and cisplatin as a first-line treatment for patients with unresectable or metastatic CCA with FGFR2 fusions or rearrangements.[8] The results of this trial are critical. A positive outcome would not only grant pemigatinib full regulatory approval (converting from accelerated/conditional status) but would also establish it as a new standard of care in the first-line setting for this molecularly defined patient population.
• Combination Therapies: Recognizing the limitations of monotherapy, particularly the development of resistance, multiple trials are exploring pemigatinib in combination regimens. The rationale is to achieve deeper, more durable responses.
• With Immunotherapy: The Phase I/II FIGHT-101 study evaluated pemigatinib plus the PD-1 inhibitor pembrolizumab. The combination was found to be tolerable with no new safety signals and demonstrated preliminary antitumor activity, with an ORR of 26.9% in a mixed population of patients with advanced malignancies.[57] Other ongoing trials are investigating combinations with different checkpoint inhibitors, such as atezolizumab and durvalumab.[59] Preclinical evidence suggests a synergistic effect, where FGFR inhibition may alter the tumor microenvironment to make it more responsive to immunotherapy.[62]
• With Anti-Angiogenic Therapy: A trial is underway combining pemigatinib with atezolizumab and the anti-VEGF agent bevacizumab, aiming to simultaneously target the tumor cell, the immune system, and the tumor vasculature.[59]

Real-World Evidence (RWE)

Several retrospective studies have been published analyzing the use and outcomes of pemigatinib in routine clinical practice, providing valuable data that complements the controlled environment of clinical trials.[63]

• Patient Population: These studies confirm that in the real world, pemigatinib is predominantly used as a second-line therapy for patients with metastatic CCA, consistent with its approved indication. The patient populations in these studies were notably diverse, including a higher proportion of racial and ethnic minorities than was enrolled in the pivotal trial.[63]
• Efficacy: Real-world outcomes have been broadly consistent with, and in some cases exceeded, the results of the FIGHT-202 trial. A US-based retrospective chart review of 120 patients reported a median real-world PFS (rwPFS) of 7.4 months, which aligns closely with the 6.9 months reported in FIGHT-202.[63] A joint analysis of French and Italian cohorts reported a median PFS of 8.7 months.[68]
• A Notable Discrepancy: A striking finding from the real-world data is a consistently higher overall response rate compared to the pivotal trial. The US study reported a rwORR of 59.2%, and the French/Italian study reported an ORR of 45.8%.[63] Both are substantially higher than the 36% ORR reported in FIGHT-202.[4] This counterintuitive finding—where real-world efficacy appears to surpass trial efficacy—may be attributable to several factors. It could reflect a selection bias in clinical practice, where clinicians may be more likely to prescribe the therapy to patients with better performance status or lower disease burden than the average trial participant. Alternatively, it could suggest that the controlled setting of the clinical trial may have, for various reasons, underestimated the drug's true clinical benefit in a broader, more heterogeneous population. This discrepancy warrants further investigation but suggests the real-world impact of pemigatinib may be even greater than indicated by the registration trial data.

Table 5: Indirect Comparison of FGFR Inhibitors in Second-Line Cholangiocarcinoma

Drug Comparison	Efficacy Outcome	Adjusted Hazard Ratio / Odds Ratio (95% CI)	Statistical Significance
Futibatinib vs. Pemigatinib	Overall Survival (OS)	HR: 0.83 (0.51–1.36)	No
	Progression-Free Survival (PFS)	HR: 0.89 (0.62–1.29)	No
	Objective Response Rate (ORR)	OR: 1.43 (0.78–2.65)	No
	Duration of Response (DOR)	HR: 0.75 (0.37–1.51)	No

Data from unanchored matching-adjusted indirect comparison (MAIC) analysis. A Hazard Ratio (HR) < 1.0 or Odds Ratio (OR) > 1.0 favors futibatinib. Data sourced from.[50]

Conclusion and Expert Recommendations

Pemigatinib has unequivocally established a new standard of care for patients with previously treated, unresectable or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements, and for patients with relapsed or refractory myeloid/lymphoid neoplasms with FGFR1 rearrangements. As a potent and selective inhibitor of FGFR1-3, its development and approval represent a landmark achievement in precision oncology for these diseases. The clinical utility of pemigatinib is fundamentally dependent on the upfront use of comprehensive genomic profiling to identify the small but significant subset of patients who stand to benefit, making companion diagnostics an indispensable component of the treatment paradigm.

The successful integration of pemigatinib into clinical practice requires a thorough understanding of its unique, on-target safety profile. Proactive and multidisciplinary management of characteristic adverse events, particularly ocular toxicities and hyperphosphatemia, is essential to maintain treatment tolerability, optimize dosing, and maximize the duration of clinical benefit for patients.

Looking forward, the field must address the key clinical challenges of primary and acquired resistance. The elucidation of specific resistance mechanisms, such as gatekeeper mutations in the FGFR2 kinase domain, provides a clear path forward for rational drug development and therapeutic sequencing.

Based on this comprehensive analysis, the following expert recommendations are proposed:

1. Routine Post-Progression Molecular Testing: To overcome acquired resistance, it is recommended that molecular testing (via tissue or liquid biopsy) be considered at the time of disease progression on pemigatinib. Identifying the specific mechanism of resistance (e.g., on-target mutation vs. bypass pathway activation) will be critical for guiding the rational selection of subsequent therapies, including next-generation covalent FGFR inhibitors.
2. Prioritization of Combination Therapy Research: While pemigatinib monotherapy is effective, responses are not universal and resistance is inevitable. The preliminary data for combinations with immunotherapy are encouraging. Further investigation of these combinations, as well as combinations with other targeted and cytotoxic agents, should be a high priority to deepen initial responses and prolong their durability.
3. Completion and Analysis of FIGHT-302: The results of the Phase III FIGHT-302 trial are eagerly awaited. A positive outcome will be pivotal in confirming pemigatinib's clinical benefit and potentially establishing it as a first-line standard of care, which would significantly alter the treatment landscape for newly diagnosed patients with FGFR2-rearranged cholangiocarcinoma.
4. Investigation of Real-World Efficacy Signals: The discrepancy between the objective response rates observed in the pivotal FIGHT-202 trial and the higher rates reported in real-world evidence studies is a significant finding. Further research is warranted to understand the factors contributing to this difference, which could include patient selection criteria, differences in response assessment in clinical practice, or other real-world variables. Elucidating these factors will provide a more complete picture of pemigatinib's clinical value.

Works cited

1. Pemigatinib: Uses, Interactions, Mechanism of Action | DrugBank Online, accessed June 16, 2025, https://go.drugbank.com/drugs/DB15102
2. What is the mechanism of Pemigatinib? - Patsnap Synapse, accessed June 16, 2025, https://synapse.patsnap.com/article/what-is-the-mechanism-of-pemigatinib
3. Pemigatinib | C24H27F2N5O4 | CID 86705695 - PubChem, accessed June 16, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Pemigatinib
4. Pemazyre First FDA-Approved Therapy for Cholangiocarcinoma plus FGFR2 Fusion, accessed June 16, 2025, https://oncpracticemanagement.com/issues/2020/june-2020-vol-10-no-6/202006-pemazyre-first-fda-approved-therapy-for-cholangiocarcinoma-plus-fgfr2-fusion
5. Pemazyre (Pemigatinib) First Targeted Therapy FDA Approved for Cholangiocarcinoma with FGFR2 Biomarker - American Health & Drug Benefits, accessed June 16, 2025, https://www.ahdbonline.com/issues/2020/august-2020-vol-13-payers-guide/pemazyre-pemigatinib-first-targeted-therapy-fda-approved-for-cholangio-carcinoma-with-fgfr2-biomarker
6. Evaluation of Pemigatinib Efficacy in FGFR-Altered Advanced Solid Tumours Led to Identification of New Therapeutic Areas for FGFR Inhibition and Drug Failure Mechanisms | ESMO, accessed June 16, 2025, https://www.esmo.org/oncology-news/evaluation-of-pemigatinib-efficacy-in-fgfr-altered-advanced-solid-tumours-led-to-identification-of-new-therapeutic-areas-for-fgfr-inhibition-and-drug-failure-mechanisms
7. Safety and efficacy of pemigatinib in patients with cholangiocarcinoma: a systematic review, accessed June 16, 2025, https://jgo.amegroups.org/article/view/99315/html
8. FIGHT-302: first-line pemigatinib vs gemcitabine plus cisplatin for ..., accessed June 16, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC9892961/
9. Real-world use of pemigatinib for the treatment of cholangiocarcinoma in the US | The Oncologist | Oxford Academic, accessed June 16, 2025, https://academic.oup.com/oncolo/article/30/1/oyae204/7739122
10. PEMAZYRE® for Myeloid/Lymphoid Neoplasms (MLNs)., accessed June 16, 2025, https://hcp.pemazyre.com/myeloid-lymphoid-neoplasms/
11. FIGHT-203: Phase II Trial of Pemigatinib in Patients With Myeloid/Lymphoid Neoplasms With FGFR1 Rearrangement - Practicing Clinicians Exchange, accessed June 16, 2025, https://practicingclinicians.com/activity/ecase/downloadsectionfile/AD2A36C1-14F1-4C3C-946B-B5449DD94386
12. PEMAZYRE® Efficacy Results from its FIGHT-203 Study., accessed June 16, 2025, https://hcp.pemazyre.com/myeloid-lymphoid-neoplasms/efficacy
13. Pemazyre® (pemigatinib) - Incyte Medical Information, accessed June 16, 2025, https://www.incytemi.com/document/Product%20Resources/MSL-PEM-US-0012%20-%20Pemigatinib%20CCA%20Prescribing%20Information%20(Mar%202025).pdf
14. Clinicogenomic Analysis of FGFR2-Rearranged ... - AACR Journals, accessed June 16, 2025, https://aacrjournals.org/cancerdiscovery/article/11/2/326/3262/Clinicogenomic-Analysis-of-FGFR2-Rearranged
15. pubchem.ncbi.nlm.nih.gov, accessed June 16, 2025, https://pubchem.ncbi.nlm.nih.gov/compound/Pemigatinib#:~:text=Pemigatinib%20is%20a%20small%20molecule,signalling%20pathways%20in%20tumour%20cells.
16. PRESCRIBING INFORMATION PEMAZYRE® (pemigatinib) 4.5, 9, 13.5 mg tablets contains Microcrystalline cellulose (E-460), Sodium s, accessed June 16, 2025, https://www.pemazyre.co.uk/prescribing-information
17. Patient Terms & Conditions | IncyteCARES for PEMAZYRE® (pemigatinib), accessed June 16, 2025, https://hcp.incytecares.com/oncology-hematology/pemazyre/terms-and-conditions
18. PEMAZYRE® (pemigatinib) Safety Profile & Side Effects, accessed June 16, 2025, https://hcp.pemazyre.com/safety-side-effects
19. PEMAZYRE® (pemigatinib) Managing Adverse Reactions, accessed June 16, 2025, https://hcp.pemazyre.com/adverse-reactions
20. PEMAZYRE® (pemigatinib) adverse event management and dosing guide, accessed June 16, 2025, https://www.pemazyre.co.uk/dosing-guide
21. 1 This label may not be the latest approved by FDA. For current labeling information, please visit https://www.fda.gov/drugsatf, accessed June 16, 2025, https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213736s000lbl.pdf
22. FDA grants accelerated approval to pemigatinib for cholangiocarcinoma with an FGFR2 rearrangement or fusion, accessed June 16, 2025, https://www.fda.gov/drugs/resources-information-approved-drugs/fda-grants-accelerated-approval-pemigatinib-cholangiocarcinoma-fgfr2-rearrangement-or-fusion
23. FDA Approval Summary: Pemigatinib for Previously Treated, Unresectable Locally Advanced or Metastatic Cholangiocarcinoma with FGFR2 Fusion or Other Rearrangement - PubMed, accessed June 16, 2025, https://pubmed.ncbi.nlm.nih.gov/36206041/
24. Final Results from the FIGHT-202 Trial of Pemigatinib in Metastatic CCA | CCA News Online, accessed June 16, 2025, https://ccanewsonline.com/special-issues/2022-year-in-review-cca/final-results-from-the-fight-202-trial-of-pemigatinib-in-metastatic-cca
25. Updated Results of the FIGHT-202 Study Reinforced the Efficacy and Safety of Pemigatinib for Previously Treated Locally Advanced/Metastatic CCA, accessed June 16, 2025, https://www.ccanewsonline.com/special-issues/2021-year-in-review-cca/2807:updated-results-of-the-fight-202-study-reinforced-the-efficacy-and-safety-of-pemigatinib-for-previously-treated-locally-advanced-metastatic-cca
26. Efficacy and Safety of Pemigatinib in Subjects With Advanced/Metastatic or Surgically Unresectable Cholangiocarcinoma Who Failed Previous Therapy - (FIGHT-202) - National Cancer Institute, accessed June 16, 2025, https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCT02924376
27. Pemigatinib trial seeks to build on targeted advances in cholangiocarcinoma - Mayo Clinic, accessed June 16, 2025, https://www.mayoclinic.org/medical-professionals/cancer/news/pemigatinib-trial-seeks-to-build-on-targeted-advances-in-cholangiocarcinoma/mac-20505667
28. Clinical Review - Pemigatinib (Pemazyre) - NCBI Bookshelf, accessed June 16, 2025, https://www.ncbi.nlm.nih.gov/books/NBK603639/
29. Behind the FDA Approval: Pemigatinib for R/R Myeloid/Lymphoid Neoplasms, accessed June 16, 2025, https://www.targetedonc.com/view/behind-the-fda-approval-pemigatinib-for-r-r-myeloid-lymphoid-neoplasms
30. Dosing and administration guide - Pemazyre, accessed June 16, 2025, https://hcp.pemazyre.com/pdf/DosingAdminGuide.pdf
31. PEMAZYRE® (pemigatinib) - Prescribing Information, accessed June 16, 2025, https://www.pemazyre.com/pemazyre-prescribing-information
32. PEMAZYRE® (pemigatinib) Access & Support | 4-Year Analysis, accessed June 16, 2025, https://hcp.pemazyre.com/4year-analysis
33. Pemigatinib Adverse Events and Management Strategies - Incyte Medical Information, accessed June 16, 2025, https://www.incytemi.com/document/Product%20Resources/MSL-PEM-US-0021%20-%20Pemigatinib%20AEs%20and%20Management%20Strategies%20(March%202025).pdf
34. Pemigatinib: uses, dosing, warnings, adverse events, interactions, accessed June 16, 2025, https://www.oncologynewscentral.com/drugs/monograph/179187-320027/pemigatinib-oral
35. Pemigatinib Monograph for Professionals - Drugs.com, accessed June 16, 2025, https://www.drugs.com/monograph/pemigatinib.html
36. Pemigatinib (Pemazyre): Uses in Cancer, Side effects, Dosage, Expectation and more, accessed June 16, 2025, https://oncodaily.com/drugs/pemigatinib-pemazyre
37. Pemazyre - opinion on variation to marketing authorisation ..., accessed June 16, 2025, https://www.ema.europa.eu/en/medicines/human/variation/pemazyre
38. pemigatinib | Ligand page | IUPHAR/BPS Guide to PHARMACOLOGY, accessed June 16, 2025, https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?tab=clinical&ligandId=9767
39. EMA Approves New Treatment Option for Certain Cholangiocarcinoma Patients, accessed June 16, 2025, https://digestivecancers.eu/ema-approves-new-treatment-option-for-certain-cholangiocarcinoma-patients/
40. View of Pemigatinib (Pemazyre) - Canadian Journal of Health Technologies, accessed June 16, 2025, https://canjhealthtechnol.ca/index.php/cjht/article/view/pc0252r/743
41. Summary Basis of Decision for Pemazyre - Drug and Health Products Portal, accessed June 16, 2025, https://dhpp.hpfb-dgpsa.ca/review-documents/resource/SBD00576
42. In which countries is Pemigatinib approved? - Patsnap Synapse, accessed June 16, 2025, https://synapse.patsnap.com/article/in-which-countries-is-pemigatinib-approved
43. FoundationOne®CDx is now FDA-approved as a companion diagnostic for PEMAZYRE™ (pemigatinib), accessed June 16, 2025, https://ce.mayo.edu/sites/default/files/Pemazyre%20FGFR2_Postcard_Announcement_052020.pdf
44. FDA Approves FoundationOne CDx as Pemigatinib Companion Diagnostic in FGFR2+ Cholangiocarcinoma - OncLive, accessed June 16, 2025, https://www.onclive.com/view/fda-approves-foundationone-cdx-as-pemigatinib-companion-diagnostic-in-emfgfr2em-cholangiocarcinoma
45. FDA Approves FoundationOne CDx as Pemigatinib Companion Diagnostic in FGFR2+ Cholangiocarcinoma - OncLive, accessed June 16, 2025, https://www.onclive.com/view/fda-approves-foundationone-cdx-as-pemigatinib-companion-diagnostic-in-emfgfr2em-cholangiocarcinoma/1000
46. Feb 16,2021 | Chugai Obtains Approval for Use of FoundationOne CDx Cancer Genomic Profile as a Companion Diagnostic for Pemigatinib for Patients with FGFR2 Fusion Positive Biliary Tract Cancer | News, accessed June 16, 2025, https://www.chugai-pharm.co.jp/english/news/detail/20210216170001_802.html
47. FoundationOne®CDx Technical Information Foundation Medicine, Inc. 150 Second Street, Cambridge, MA 02141 Phone: 617.418.2200 I - accessdata.fda.gov, accessed June 16, 2025, https://www.accessdata.fda.gov/cdrh_docs/pdf17/P170019S014C.pdf
48. FGFR Inhibition in Cholangiocarcinoma: Overcoming Acquired Resistance, accessed June 16, 2025, https://theoncologypharmacist.com/web-exclusives/fgfr-inhibition-in-cholangiocarcinoma-overcoming-acquired-resistance-top
49. Landscape of Clinical Resistance Mechanisms to FGFR Inhibitors in FGFR2-Altered Cholangiocarcinoma - PMC, accessed June 16, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10767308/
50. Matching-Adjusted Indirect Comparison of Futibatinib Versus Chemotherapy and Pemigatinib in Cholangiocarcinoma Patients with FGFR2 Fusions/Rearrangements - ISPOR, accessed June 16, 2025, https://www.ispor.org/docs/default-source/euro2022/isporeu22thomco78-pdf.pdf?sfvrsn=6ebb5668_0
51. Indirect treatment comparison of futibatinib with chemotherapy and pemigatinib in cholangiocarcinoma with FGFR2 fusions/rearrangements. | Journal of Clinical Oncology - ASCO Publications, accessed June 16, 2025, https://ascopubs.org/doi/10.1200/JCO.2022.40.4_suppl.440
52. Cross-Comparison of Clinical Trials Assessing Futibatinib and Pemigatinib versus Chemotherapy in Patients with CCA and FGFR2 Fusion or Other Rearrangements, accessed June 16, 2025, https://ccanewsonline.com/special-issues/2022-year-in-review-cca/2966:cross-comparison-of-clinical-trials-assessing-futibatinib-and-pemigatinib-versus-chemotherapy-in-patients-with-cca-and-fgfr2-fusion-or-other-rearrangements
53. Pemazyre (pemigatinib) vs Truseltiq (infigratinib) - Everyone.org, accessed June 16, 2025, https://everyone.org/explore/compare?id1=391&id2=445
54. Infigratinib for the Treatment of Metastatic or Locally Advanced Cholangiocarcinoma With Known FGFR2 Gene Fusions or Rearrangements - PubMed Central, accessed June 16, 2025, https://pmc.ncbi.nlm.nih.gov/articles/PMC10634393/
55. Practical Issues in the Use of FGFR Inhibitors for Advanced Cholangiocarcinoma, accessed June 16, 2025, https://sponsored.harborsidestudio.com/practical-issues-in-the-use-of-fgfr-inhibitors-for-advanced-cholangiocarcinoma/
56. FIGHT-302: Phase III study of first-line (1L) pemigatinib (PEM) versus gemcitabine (GEM) plus cisplatin (CIS) for cholangiocarcinoma (CCA) with FGFR2 fusions or rearrangements. - ASCO Publications, accessed June 16, 2025, https://ascopubs.org/doi/10.1200/JCO.2020.38.4_suppl.TPS592
57. Safety and efficacy of pemigatinib plus pembrolizumab combination therapy in patients (pts) with advanced malignancies: Results from FIGHT-101, an open-label phase I/II study. | Journal of Clinical Oncology - ASCO Publications, accessed June 16, 2025, https://ascopubs.org/doi/10.1200/JCO.2020.38.15_suppl.3606
58. Open-label, dose-escalation FIGHT-101 study of pemigatinib combined with targeted therapy, chemotherapy, or immunotherapy in patients with advanced malignancies - PubMed, accessed June 16, 2025, https://pubmed.ncbi.nlm.nih.gov/38986210/
59. Phase IIb trial of pemigatinib in combination with atezolizumab and bevacizumab for treatment of advanced cholangiocarcinoma with FGFR2 fusion, accessed June 16, 2025, http://www.cholangiocarcinoma.org/trials/phase-iib-trial-of-pemigatinib-in-combination-with-atezolizumab-and-bevacizumab-for-treatment-of-advanced-cholangiocarcinoma-with-fgfr2-fusion-2/
60. Pemigatinib and Atezolizumab With or Without Bevacizumab for Treatment of Patients With Advanced or Metastatic Cholangiocarcinoma with FGFR2 Fusion - National Cancer Institute, accessed June 16, 2025, https://www.cancer.gov/research/participate/clinical-trials-search/v?id=NCI-2024-04693
61. Pemigatinib Combined With Durvalumab for Previously Treated Biliary Tract Carcinoma, accessed June 16, 2025, https://connect.careboxhealth.com/en-US/trial/listing/522535
62. A multi-center, single-arm, phase II study of pemigatinib combined with immune checkpoint inhibitor in FGFR1/2/3 alteration advanced solid tumor. - ASCO Publications, accessed June 16, 2025, https://ascopubs.org/doi/10.1200/JCO.2025.43.16_suppl.TPS2692
63. Real-world use of pemigatinib for the treatment of ... - PubMed, accessed June 16, 2025, https://pubmed.ncbi.nlm.nih.gov/39173023/
64. Real-world use of pemigatinib (pemi) for cholangiocarcinoma (CCA) among racial and ethnic minorities in the United States. - ASCO Publications, accessed June 16, 2025, https://ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.461
65. Real-world (RW) characteristics, treatment patterns, and outcomes of patients with cholangiocarcinoma (CCA) treated with pemigatinib. - ASCO Publications, accessed June 16, 2025, https://ascopubs.org/doi/10.1200/JCO.2024.42.3_suppl.444
66. Real-world Data Supports Findings from FIGHT-202 in Cholangiocarcinoma, accessed June 16, 2025, https://www.cancernetwork.com/view/real-world-data-supports-findings-from-fight-202-in-cholangiocarcinoma
67. Real-world use of pemigatinib for the treatment of cholangiocarcinoma in the US - Oxford Academic, accessed June 16, 2025, https://academic.oup.com/oncolo/advance-article-pdf/doi/10.1093/oncolo/oyae204/58894151/oyae204.pdf
68. Pemigatinib for patients with previously treated, locally advanced or metastatic cholangiocarcinoma harboring FGFR2 fusions or rearrangements: A joint analysis of the French PEMI-BIL and Italian PEMI-REAL cohort studies - PubMed, accessed June 16, 2025, https://pubmed.ncbi.nlm.nih.gov/38340384/