Pemazyre (pemigatinib) - 2 indications

Scroll down for additional information on each indication:

• for the treatment of metastatic cholangiocarcinoma; approved April 2020 
• for the treatment of relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement; approved August 2022

General Information

Pemazyre (pemigatinib) is a kinase inhibitor.

Pemazyre is specifically 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.
• the treatment of adults with relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement

Pemazyre is supplied as a tablet for oral administration. Scroll down for recommended dosing/administration for each indication. 

Mechanism of Action

Pemazyre (pemigatinib)  is a small molecule kinase inhibitor that targets FGFR1, 2 and 3 with IC50 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. Pemigatinib exhibited anti-tumor activity in mouse xenograft models of human tumors with FGFR1, FGFR2, or FGFR3 alterations resulting in constitutive FGFR activation including a patient-derived xenograft model of cholangiocarcinoma that expressed an oncogenic FGFR2Transformer-2 beta homolog (TRA2b) fusion protein.

Side Effects

Adverse effects associated with the use of Pemazyre may include, but are not limited to, the following:

• 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

Indication 1 - for the treatment of metastatic cholangiocarcinoma

approved April 2020 

Dosing/Administration

The recommended dosage of Pemazyre 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. Take Pemazyre with or without food at approximately the same time every day.  Swallow tablets whole. Do not crush, chew, split, or dissolve tablets. If the patient misses a dose of Pemazyre by 4 or more hours or if vomiting occurs, resume dosing with the next scheduled dose. 

Clinical Trial Results

Pemazyre was 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).

The FDA approval of Pemazyre was based on data from FIGHT-202, a multi-center, open-label, single-arm study in adult (age ≥18 years) patients with previously treated, locally advanced or metastatic cholangiocarcinoma with documented FGFR2 fusion or rearrangement. Patients were enrolled into one of three cohorts – Cohort A (FGFR2 fusions or rearrangements), Cohort B (other FGF/FGFR genetic alterations) or Cohort C (no FGF/FGFR genetic alterations). All patients received 13.5 mg Pemazyre orally once daily (QD) on a 21-day cycle (two weeks on/one week off) until radiological disease progression or unacceptable toxicity. The primary endpoint of FIGHT-202 was overall response rate (ORR) in Cohort A, assessed by independent review per RECIST v1.1. Secondary endpoints included duration of response (DOR). In patients harboring FGFR2 fusions or rearrangements (Cohort A), Pemazyre monotherapy resulted in an overall response rate of 36% and median DOR of 9.1 months.

Indication 2 - for the treatment of relapsed or refractory myeloid/lymphoid neoplasms (MLNs) with FGFR1 rearrangement

approved August 2022

Dosing/Administration

Recommended dosage is 13.5 mg orally once daily. Continue treatment until disease progression or unacceptable toxicity. Take Pemazyre with or without food at approximately the same time every day.  Swallow tablets whole. Do not crush, chew, split, or dissolve tablets. If the patient misses a dose of Pemazyre by 4 or more hours or if vomiting occurs, resume dosing with the next scheduled dose. 

Clinical Trial Results

The FDA approval was based on data from the Phase 2 FIGHT-203 study, a multicenter open-label, single-arm trial that evaluated the safety and efficacy of Pemazyre in 28 patients with relapsed or refractory MLNs with FGFR1 rearrangement. Patients could have relapsed after allogeneic hematopoietic stem cell transplantation (allo-HSCT) or after a disease modifying therapy or were not a candidate for allo-HSCT or other disease modifying therapies. 

In patients with chronic phase in the marrow with or without EMD (N = 18), the complete response (CR) rate was 78%. The median time to response of CR was 104 days. The median duration of CR was not reached. In patients with blast phase in the marrow with or without EMD (N = 4), two patients achieved a CR (duration: 1+ and 94 days). In patients with EMD only (N = 3), one patient achieved a CR (duration: 64+ days). For all patients (N = 28 including three patients without evidence of morphologic disease) the complete cytogenetic response rate was 79%.