Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Pemigatinib · 10 trials · 19 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).
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.
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). |
| 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. |
| 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). |
| Durvalumab | DRUG | Durvalumab 1500 mg IV |
| Computed Tomography (CT) | PROCEDURE | Undergo CT scan |
| Magnetic Resonance Imaging | PROCEDURE | Undergo MRI |
| Optical Coherence Tomography | PROCEDURE | Undergo OCT |
| Bone Scan | PROCEDURE | Undergo whole body bone scan |
| Ophthalmoscopy | PROCEDURE | Undergo dilated ophthalmoscopy |
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...