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    DRUG:

    PHI-101

    i
    Other names: PHI-101
    Company:
    Pharos iBT
    Drug class:
    FLT3 inhibitor, Chk2 inhibitor
    Related drugs:
    1year
    Evaluation of Synergistic Anti-Leukemic Efficacy of PHI-101 in Preclinical Model of FLT3-ITD Acute Myeloid Leukemia (ASH 2023)
    Study Design and Combination effects of simultaneous versus sequential treatment of PHI-101 with other agents, including daunorubicin, cytarabine, venetoclax (Ven), and azacytidine (Aza) were tested using human leukemia cell lines harboring FLT3-ITD mutations (MV4-11, Molm13, Molm14) or FLT3-wild type as controls...The GI 50 of the gilteritinib was 5... Treatment of AML cells with the combination of Ven or Aza with PHI-101 in vitro induced rapid induction of apoptosis and inhibition of cell growth that showed significant synergy. In vivo data showed improved efficacy for the combination treatment with these agents. In vitro and in vivo data from the preclinical AML models provides a rationale to evaluate the activity of PHI-101 in combination for patients who are ineligible for more intensive chemotherapeutic induction therapy.
    Preclinical • PARP Biomarker • IO biomarker
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    FLT3 (Fms-related tyrosine kinase 3) • BCL2 (B-cell CLL/lymphoma 2) • ANXA5 (Annexin A5)
    |
    FLT3-ITD mutation • FLT3 mutation • BCL2 expression • FLT3 wild-type
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    Venclexta (venetoclax) • Xospata (gilteritinib) • azacitidine • daunorubicin • PHI-101
    1year
    PHI-101 As a Potent Next-Generation FLT3 Inhibitor, Overcome Resistances in Previously Treated Patients with FLT3-ITD or TKD Acute Myeloid Leukemia: Results of a Phase Ia/Ib Clinical Trial (ASH 2023)
    Ten pts were R/R following previous treatment with other FLT3 inhibitors (gilteritinib, quizartinib, midostaurin, or HM43239). In dose-escalating phase Ia clinical trials, PHI-101 was well tolerated at all dose levels with no DLTs. Phase Ib dose-expansion trials with 160 mg daily dosing are currently ongoing. PHI-101 has delivered CRcs at 120 mg and 160 mg.
    Clinical • P1 data
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    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3 D835 • FLT3 N676K • FLT3 wild-type • FLT3 D835E
    |
    Xospata (gilteritinib) • Rydapt (midostaurin) • Vanflyta (quizartinib) • PHI-101 • tuspetinib (HM43239)
    over1year
    Chk2 Inhibitor for Recurrent EpitheliAl periToneal, fallopIan or oVarian cancEr (CREATIVE Phase IA Trial) (clinicaltrials.gov)
    P1, N=36, Recruiting, Seoul National University Hospital | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Dec 2023
    Trial completion date • Trial primary completion date
    |
    HRD (Homologous Recombination Deficiency)
    |
    HRD
    |
    PHI-101
    2years
    A Potent Small Molecule Inhibitor of FLT3, PHI-101 Overcomes Resistance in Acute Myeloid Leukemia: Efficacy and PK/PD Profile in Phase 1 First in Human Study (ASH 2022)
    Seventy percent of enrolled patients had more than 3 prior anti-leukemic treatment attempts, and four patients had relapsed or refractory disease after treatment with other FLT3 inhibitors including gilteritinib, quizartinib, or HM43239. A dose-escalating phase 1a clinical data of PHI-101, which reflects up to cohort 4 of the study, indicates that PHI-101 generated potent FLT3 inhibition leading to encouraging anti-leukemic responses in R/R AML patients, including in those with prior FLT3 TKI therapeutic failure. PHI-101 showed good tolerance and favorable safety profile and reduced leukemic blasts significantly with 28-day dosing. PHI-101 sustained its activity to clear FLT3-ITD and/or FLT3-TKD mutations including D835Y or N676K identified in AML patients.
    Clinical • P1 data • PK/PD data
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation • FLT3 D835Y • FLT3 D835 • FLT3 N676K
    |
    Xospata (gilteritinib) • Vanflyta (quizartinib) • PHI-101 • tuspetinib (HM43239)
    almost3years
    A phase IA dose-escalation study of PHI-101, a new checkpoint kinase 2 inhibitor, for platinum-resistant recurrent ovarian cancer. (PubMed, BMC Cancer)
    PHI-101 is the first orally available Chk2 inhibitor, expected to show effectiveness in treating recurrent ovarian cancer. Through this CREATIVE trial, DLT and MTD of this new targeted therapy can be confirmed to find the recommended dose for the phase II clinical trial. This study may contribute to developing a new combination regimen for the treatment of ovarian cancer.
    P1 data • Clinical Trial,Phase I • Journal
    |
    CHEK2 (Checkpoint kinase 2)
    |
    PHI-101
    3years
    A Phase 1a/1b First in Human Study of PHI-101, a Potent Small Molecule Inhibitor of FLT3 in Relapsed and Refractory Acute Myeloid Leukemia (ASH 2021)
    In preclinical studies utilizing primary human FLT3-ITD leukemia cells, PHI-101 showed increased anti-leukemic activity compared to gilteritinib based on increased survival in mice transplanted with these samples. PHI-101 is a next-generation FLT3 inhibitor that showed a potent anti-leukemic activity and improved efficacy in primary AML samples harboring FLT3/ITD and FLT3/TKD mutations in preclinical studies. The current analysis of this trial indicated that PHI-101 is a very effective FLT3 inhibitor for both refractory and relapsed AML patients, including those that have relapsed on other FLT3 TKI. The assessments of safety, tolerability, and PK of PHI-101 to determine the recommended dose for expansion are ongoing in the Phase 1a clinical trial.
    P1 data
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation • FLT3 mutation • FLT3-TKD mutation
    |
    Xospata (gilteritinib) • PHI-101
    over3years
    Evaluation of the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of PHI 101 for the Treatment of AML (clinicaltrials.gov)
    P1a/1b, N=42, Recruiting, Seoul National University Hospital
    New P1 trial
    |
    FLT3 (Fms-related tyrosine kinase 3)
    |
    FLT3-ITD mutation
    |
    PHI-101
    almost4years
    Chk2 Inhibitor for Recurrent EpitheliAl periToneal, fallopIan or oVarian cancEr (CREATIVE Phase IA Trial) (clinicaltrials.gov)
    P1, N=36, Recruiting, Seoul National University Hospital | Not yet recruiting --> Recruiting
    Clinical • Enrollment open
    |
    HRD (Homologous Recombination Deficiency)
    |
    HRD
    |
    PHI-101
    4years
    Chk2 Inhibitor for Recurrent EpitheliAl periToneal, fallopIan or oVarian cancEr (CREATIVE Phase IA Trial) (clinicaltrials.gov)
    P1, N=36, Not yet recruiting, Seoul National University Hospital
    Clinical • New P1 trial
    |
    HRD (Homologous Recombination Deficiency)
    |
    HRD
    |
    PHI-101