Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Label indication 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. ( 1 , 2.1 ) This indication is approved under accelerated approval based on overall response rate and duration of response. FDA label
Also known as Pemazyre®, INCB 054828, INCB 54828
Pemigatinib · 13 trials · 45 indications
Proportion of patients experiencing an objective response or at least a 30% decrease in tumor growth kinetics at disease progression on study treatment as compared to the one calculated from the two pre-treatment tumor evaluations. The tumor kinetics variation is measured by the tumor growth ratio defined as the ratio of the slope of tumor growth on treatment (between the nadir and disease progression) and the slope of tumor growth before treatment. The sum of the diameters of target lesions according to RECIST 1.1 will be calculated on each patient's imaging by the Blinded Independent Central Review (BICR).
Defined as having a confirmed best response of complete response (CR) or partial response (PR), as determined by an independent central review (ICR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.
Defined as the date of start of treatment to the date of death due to any cause. Will be analyzed using the Kaplan Meier method. Survival rate at 12 months and median OS will be estimated along with 95% confidence intervals from the Kaplan Meier distribution.
The objective response rate is defined as the rate of participants with a complete response or partial response, calculated using RECIST 1.1.
ORR will include confirmed complete response (CR) + confirmed partial response (PR) and will be determined as per RECIST version 1.1. A confirmed response is defined to be either a CR or PR noted as the objective status on 2 consecutive evaluations at least 4 weeks apart.
To assess the efficacy of pemigatinib in subjects with R/R MCL.
To assess the efficacy of pemigatinib in subjects with R/R MZL.
The proportion of patients with a best overall response of complete response (CR) or partial response (PR). Overall response rate assessed per RECIST v1.1. Will be evaluated in all patients who received at least 80% of the recommended dose of pemigatinib averaged over a 9-week period. ORR will be calculated along with its 95% confidence interval
ORR was defined as the percentage of participants who achieved a complete response (CR) or a partial response (PR) based on Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Response was determined by an Independent Central Radiology (ICR) review. CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions.
CR was defined as the presence of all of the following improvements: (1) bone marrow: ≤5% myeloblasts (including monocytic blast equivalent) and no lymphoblasts, with normal maturation of all cell lines, and return to age-adjusted normal cellularity; (2) osteomyelofibrosis absent or equal to "mild reticulin fibrosis" (Grade 1 or less fibrosis); (3) peripheral blood: white blood cells (WBC) ≤10 x 10\^9 cells/Liter (L); hemoglobin (Hgb) ≥11 grams per deciliter (g/dL); platelets ≥100 x 10\^9/L and ≤450 x 10\^9/L; neutrophils ≥1.0 x 10\^9/L; blasts = 0%; neutrophil precursors reduced to ≤2%; monocytes ≤1 x 10\^9/L; eosinophils ≤0.5 x 10\^9/L; (4) extramedullary disease: complete resolution of extramedullary disease present before therapy (e.g., lymphadenopathy), including palpable hepatosplenomegaly. Persistent low-level dysplasia was permitted given subjectivity of assignment of dysplasia. Response criteria by investigator assessment were the same for chronic phase (CP) and blast phase (BP).
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) at any post-Baseline visit prior to first progressive disease (PD), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. ORR was based on central genomics laboratory results. Response was based on review of scans by an independent centralized radiological review committee.
ORR was defined as the percentage of participants with a best overall response of complete response (CR) or partial response (PR) at any post-Baseline visit prior to first progressive disease (PD), per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1). CR: disappearance of all target and non-target lesions and no appearance of any new lesions. Any pathological lymph nodes (whether target or non-target) must have a reduction in the short axis to \<10 millimeters (mm). PR: complete disappearance or at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference the baseline sum diameters, no new lesions, and no progression of non-target lesions. Response was based on review of scans by an independent centralized radiological review committee. Response was confirmed.
Will be summarized using the proportion and exact binomial confidence interval. DLTs will be summarized at each dose level by severity and major organ site according to the Common Terminology Criteria for Adverse Events (CTCAE) version (v)5.0.
An AE is defined as any untoward medical occurrence associated with the use of a drug in humans, whether or not considered drug related, that occurs after a subject provides informed consent.
| Arm | Type | Description |
|---|---|---|
| pemigatinib | EXPERIMENTAL | Pemigatinib will be administered orally once daily for 2 weeks followed by a 1-week off (intermittent schedule 2/1). |
| Treatment (chemoimmunotherapy, FGFRi cycles) | EXPERIMENTAL | See Detailed Description |
| Pemigatinib + Durvalumab | EXPERIMENTAL | Pemigatinib 13.5 mg will be taken orally at the same time each day for 14 days (Day 1 through Day 14), followed by 7 days off treatment (Day 15 through Day 21) of each 21 day cycle. Durvalumab 1500 mg IV will be administered every 3 weeks on Day 1 of each 21-day cycle. |
| Treatment: All Patients | EXPERIMENTAL | The study will investigate the effectiveness of pemigatinib. |
| Pemigatinib Treament | EXPERIMENTAL | Patients receive pemigatinib PO QD on days 1-14 of each cycle. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Patients also undergo blood sample collection, CT and/or MRI, and OCT throughout the study. Patients may also undergo whole body bone scans and dilated fundoscopy as clinically indicated. |
| Cohort A: Squamous NSCLC | EXPERIMENTAL | Participants with squamous NSCLC with known or likely FGFR1-3 driver mutations outside the kinase domain or fusions/rearrangements will receive intermittent dosing. |
| Cohort B: Non-squamous NSCLC | EXPERIMENTAL | Participants with non-squamous NSCLC with known or likely FGFR1-3 driver mutations outside the kinase domain or fusions/rearrangements will receive intermittent dosing. |
| Cohort A Pemigatinib | EXPERIMENTAL | Pemigatinib in subjects with FGFR2 translocation with a documented fusion partner in central laboratory report |
| Cohort B Pemigatinib | EXPERIMENTAL | Pemigatinibin subjects with other FGF/FGFR alterations |
| Cohort C Pemigatinib | EXPERIMENTAL | Pemigatinib in subjects negative for FGF/FGFR alteration |
| Cohort A-ID (Intermittent Dose) Pemigatinib | EXPERIMENTAL | Pemigatinib in subjects with FGFR3 mutations or fusions. |
| Cohort A-CD (Continuous Dose) Pemigatinib | EXPERIMENTAL | Pemigatinib in subjects with FGFR3 mutations or fusions. |
| Treatment (cytarabine, daunorubicin, pemigatinib) | EXPERIMENTAL | INDUCTION: Patients receive cytarabine IV on days 1-7, daunorubicin IV on days 1-3, and pemigatinib PO QD on days 8-21 in the absence of disease progression or unacceptable toxicity. Patients with hematologic count recovery (assessed between days 25-42) after induction proceed to consolidation therapy. Patients undergo ECHO during screening and as clinically indicated on study. Patients undergo blood sample collection and bone marrow aspirate and biopsy during screening and cycle 11 day 21 on study. CONSOLIDATION: Patients receive high dose cytarabine IV BID on days 1, 3, and 5 of each cycle, and pemigatinib PO QD on days 8-21 of each cycle. Treatment repeats every 28 days for up to 4 cycles in the absence of disease progression of unacceptable toxicity. Patients undergo ECHO as clinically indicated and blood sample collection and bone marrow biopsy and aspirate at the end of consolidation. |
| Name | Type | Description |
|---|---|---|
| Pemigatinib | DRUG | Pemigatinib will be administered orally once daily for 2 weeks followed by a 1-week off (intermittent schedule 2/1). |
| Biospecimen Collection | PROCEDURE | Undergo blood sample collection |
| Cisplatin | DRUG | Given IV |
| Computed Tomography | PROCEDURE | Undergo CT scan |
| Durvalumab | BIOLOGICAL | Given IV |
| Gemcitabine | DRUG | Given IV |
| Magnetic Resonance Imaging | PROCEDURE | Undergo MRI |
| Survey Administration | OTHER | Ancillary studies |
| Computed Tomography (CT) | PROCEDURE | Undergo CT scan |
| Optical Coherence Tomography | PROCEDURE | Undergo OCT |
| Bone Scan | PROCEDURE | Undergo whole body bone scan |
| Ophthalmoscopy | PROCEDURE | Undergo dilated ophthalmoscopy |
| Bone Marrow Aspirate | PROCEDURE | Undergo bone marrow biopsy and aspirate |
| Bone Marrow Biopsy | PROCEDURE | Undergo bone marrow biopsy and aspiratie |
| Cytarabine | DRUG | Given IV |
| Daunorubicin | DRUG | Given IV |
| Electrocardiography | PROCEDURE | Undergo ECHO |
Inclusion Criteria: 1. Histologically or cytologically confirmed solid tumor 2. Patient with locally recurrent unresectable and/or advanced or metastatic disease harbouring a FGFR1,2,3 fusion/rearrangement or mutation 3. Age ≥ 18 years 4. Eastern Cooperative Oncology Group (ECOG) performance status...
Pemigatinib is a small molecule FGFR inhibitor developed by Incyte Corporation for oncology indications. It is being studied in cholangiocarcinoma, acute myeloid leukemia, advanced pancreatic carcinoma, myeloproliferative neoplasms, and ampulla of Vater carcinoma. It is an investigational therapy in clinical development.
Pemigatinib is being evaluated for cholangiocarcinoma, including intrahepatic and advanced or metastatic forms, particularly in patients with FGFR2 fusions or rearrangements. It is also studied in biliary tract cancers and ampulla of Vater carcinoma. It remains investigational and is not approved for these uses.
Pemigatinib targets FGFR1, FGFR2, and FGFR3. It is a small molecule inhibitor of these fibroblast growth factor receptors. This mechanism is relevant in tumors with FGFR genetic alterations, such as FGFR2 fusions or rearrangements.
Pemigatinib is developed by Incyte Corporation, which trades under the ticker INCY. Incyte is the sponsor of the clinical trials evaluating pemigatinib across multiple oncology indications.
Pemigatinib is in Phase 1 development according to the overall program status, though individual trials are listed as Phase 2. It is investigational and has not been approved by the FDA for the indications being studied.
Pemigatinib is being studied in several trials, including NCT07862998 in cholangiocarcinoma, NCT07780838 in biliary tract cancers, NCT07434843 in SDH-deficient GIST, and NCT06906562 in pancreatic cancer with FGFR alterations. These trials are in Phase 2 and include biomarker-selected patients.