A Study to Evaluate the Efficacy and Safety of Pemigatinib (INCB054828) in Subjects With Myeloid/Lymphoid Neoplasms With FGFR1 Rearrangement - (FIGHT-203)

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).

Time frame: up to 2513 days (120 21-day treatment cycles)

Population: Full Efficacy-Evaluable Population: all enrolled participants with an FGFR1 rearrangement and who received at least 1 dose of study drug. For this report, the full EEP included both previously treated and treatment-naive participants. Confidence intervals were calculated based on the exact method for binomial distribution.

Duration of complete response was defined as the time from the first assessment of complete response to the earlier of the date of first worsening assessment after complete response or death due to any cause

Time frame: up to 2513 days (120 21-day treatment cycles)

Population: Full Efficacy-Evaluable Population. Only participants with a complete response were analyzed. Confidence intervals were calculated using the Brookmeyer and Crowley's method.

Duration of response was defined as the time from the first assessment of complete response or partial response to the earlier of the date of first worsening assessment after response or death due to any cause.

Time frame: up to 2513 days (120 21-day treatment cycles)

Population: Full Efficacy-Evaluable Population. Only participants with complete response or partial response were analyzed. Confidence intervals were calculated based on the exact method for binomial distribution.

An AE was 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 participant provides informed consent. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug. The severity of AEs was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4.03 Grades 1 through 4. Grade 1: mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. Grade 2: moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate activities of daily living. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care activities of daily living. Grade 4: life-threatening consequences; urgent intervention indicated.

Time frame: up to 2543 days

Population: Safety Population

An adverse event (AE) was 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 participant provides informed consent. A TEAE was defined as any AE either reported for the first time or the worsening of a pre-existing event after the first dose of study drug.

Time frame: up to 2543 days

Population: Safety Population: all enrolled participants who received at least 1 dose of study drug

Overall survival was defined as as the time from the first day of taking study drug until death due to any cause

Time frame: up to 2513 days (120 21-day treatment cycles)

Population: Full Efficacy-Evaluable Population. Confidence intervals were calculated using the Brookmeyer and Crowley's method. Participants without death observed at the time of the analysis were censored at the last date known to be alive.

CR=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/equal to mild reticulin fibrosis; (3) WBC ≤10 x 10\^9 cells/L; Hgb ≥11 g/dL; platelets ≥100 x 10\^9/L, ≤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 pre-therapy, including palpable hepatosplenomegaly. Persistent low-level dysplasia was permitted. PR=all of the following improvements: (1) reduction of bone marrow blasts/blast equivalents by 50%, but remaining \>5% of cellularity (except in cases with ≤5% bone marrow blasts at baseline); (2) normalization of peripheral blood indices per CR Criterion 3; (3) extra medullary disease response of CMR/CR or PMR/PR.

Time frame: up to 2513 days (120 21-day treatment cycles)

Population: Full Efficacy-Evaluable Population. Confidence intervals were calculated based on the exact method for binomial distribution. CMR=complete metabolic response; PMR=partial metabolic response. Response criteria by investigator assessment were the same for chronic phase (CP) and blast phase (BP).

CCyR was defined as 0% 8p11 translocated metaphases as seen on classic karyotyping with minimal of 20 metaphases, or fluorescence in situ hybridization (FISH). Loss of cytogenetic burden of disease (via FISH or classic karyotyping) was required to reach CCyR.

Time frame: up to 2513 days (120 21-day treatment cycles)

Population: Full Efficacy-Evaluable Population. Confidence intervals were calculated based on the exact method for binomial distribution.

PCyR was defined as the decrease from baseline of 50% or more 8p11 translocated metaphases as seen on classic karyotyping with minimal of 20 metaphases, or FISH.

Time frame: up to 2513 days (120 21-day treatment cycles)

Population: Full Efficacy-Evaluable Population. Confidence intervals were calculated based on the exact method for binomial distribution.

In addition, responses were assessed by CRC based on MLN IWG response criteria for myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions.

Time frame: up to 2513 days (120 21-day treatment cycles)

Population: Full Efficacy-Evaluable Population. Confidence intervals were calculated based on the exact method for binomial distribution.

PFS was defined as the time from the first date of taking study drug until the date of disease progression or until death due to any cause, whichever was earlier. Disease progression was defined as the combination of 2 major criteria, 1 major and 2 minor criteria, or 3 minor criteria from the following lists. Major criteria: (1) increase in blast count; (2) evidence of cytogenetic evolution (re-appearance of a previously present or appearance of a new cytogenetic abnormality, or increase in cytogenetic burden of disease); (3) new or worsening extramedullary disease (worsening splenomegaly or extramedullary disease outside of the spleen). Minor criteria: (1) transfusion dependence; (2) significant loss of maximal response on cytopenias ≥50% decrement from maximum remission/response in granulocytes or platelets; (3) reduction in Hgb by ≥1.5g/dL from best response or from baseline as noted on complete blood count; (4) evidence of clonal evolution (molecular).

Time frame: up to 2513 days (120 21-day treatment cycles)

Population: Full Efficacy-Evaluable Population. The confidence interval was calculated using the Brookmeyer and Crowley's method. Participants who were still alive without experiencing disease progression at the time of analysis were censored at the date of the last response assessment before the cutoff date. Participants who started a new cancer therapy before disease progression were censored at the date of last response assessment before new cancer therapy start.

In addition, responses were assessed by CRC based on MLN IWG response criteria for myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions.

Time frame: up to 2513 days (120 21-day treatment cycles)

Population: Full Efficacy-Evaluable Population. Confidence intervals were calculated based on the exact method for binomial distribution.

In addition, responses were assessed by CRC based on MLN IWG response criteria for myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions.

Time frame: up to 2513 days (120 21-day treatment cycles)

Population: Full Efficacy-Evaluable Population. Confidence intervals were calculated based on the exact method for binomial distribution.

In addition, responses were assessed by CRC based on Myeloid/Lymphoid Neoplasm International Working Group (MLN IWG) response criteria for myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions.

Time frame: up to 2513 days (120 21-day treatment cycles)

Population: Full Efficacy-Evaluable Population. Confidence intervals were calculated based on the exact method for binomial distribution.