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    DRUG:

    enozertinib (ORIC-114)

    i
    Other names: ORIC-114, VRN07
    Company:
    ORIC Pharma, Voronoi
    Drug class:
    HER2 exon 20 mutation inhibitor
    Related drugs:
    29d
    Enozertinib is a Selective, Brain-penetrant EGFR inhibitor for Treating Non-small Cell Lung Cancers with EGFR Exon 20 and Atypical Mutations. (PubMed, Cancer Res)
    Here, we describe the discovery and development of enozertinib (formerly ORIC-114), a highly brain-penetrant, orally bioavailable, irreversible inhibitor that targets EGFR exon 20 mutations with unparalleled kinome selectivity...In a phase I clinical trial of enozertinib in patients with advanced NSCLC bearing atypical mutations in EGFR, a patient with harboring an EGFR exon 20 insertion experienced sustained complete response of all systemic and brain metastases. Together, these findings identify enozertinib as a promising investigational inhibitor to meet the unmet need for brain-penetrant therapies for NSCLC with EGFR exon 20 insertions or other atypical mutations.
    Journal
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    enozertinib (ORIC-114)
    4ms
    ORIC-114-01: Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration (clinicaltrials.gov)
    P1/2, N=350, Recruiting, ORIC Pharmaceuticals | Trial completion date: Mar 2026 --> Sep 2027 | Trial primary completion date: Mar 2025 --> Sep 2026
    Trial completion date • Trial primary completion date
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • HER-2 overexpression • HER-2 amplification • EGFR exon 20 insertion • HER-2 exon 20 insertion • EGFR exon 20 mutation
    |
    carboplatin • pemetrexed • enozertinib (ORIC-114)
    10ms
    ORIC-114 in Combination with Subcutaneous Amivantamab in Patients with EGFR Exon20 Insertion Mutant NSCLC (clinicaltrials.gov)
    P1, N=76, Recruiting, ORIC Pharmaceuticals | Not yet recruiting --> Recruiting
    Enrollment open
    |
    Rybrevant (amivantamab-vmjw) • enozertinib (ORIC-114) • amivantamab SC (Ami-LC)
    10ms
    ORIC-114 in Combination with Subcutaneous Amivantamab in Patients with EGFR Exon20 Insertion Mutant NSCLC (clinicaltrials.gov)
    P1, N=76, Not yet recruiting, ORIC Pharmaceuticals
    New P1 trial
    |
    Rybrevant (amivantamab-vmjw) • enozertinib (ORIC-114) • amivantamab SC (Ami-LC)
    almost2years
    Effect of Food on the Pharmacokinetics of ORIC-114 (clinicaltrials.gov)
    P1, N=32, Completed, ORIC Pharmaceuticals | Recruiting --> Completed
    Trial completion
    |
    enozertinib (ORIC-114)
    almost2years
    Ph 1/2 Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration (clinicaltrials.gov)
    P1/2, N=280, Recruiting, ORIC Pharmaceuticals | Phase classification: P1 --> P1/2 | N=42 --> 280 | Trial completion date: Mar 2025 --> Mar 2026
    Phase classification • Enrollment change • Trial completion date
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • HER-2 overexpression • HER-2 amplification • EGFR exon 20 insertion • HER-2 exon 20 insertion • EGFR exon 20 mutation • HER-2 exon 23 mutation
    |
    carboplatin • pemetrexed • enozertinib (ORIC-114)
    2years
    Effect of Food on the Pharmacokinetics of ORIC-114 (clinicaltrials.gov)
    P1, N=32, Recruiting, ORIC Pharmaceuticals | Not yet recruiting --> Recruiting
    Enrollment open
    |
    enozertinib (ORIC-114)
    over2years
    Preclinical activity of ORIC-114, a highly selective, brain penetrant, irreversible kinase inhibitor, against atypical mutations in EGFR (ESMO 2023)
    Conclusions ORIC-114 demonstrated best-in-class properties including high free unbound exposure in brain, exquisite selectivity across the kinome, and potent activity across atypical mutations in EGFR, including PACC mutations and exon 20 insertion mutations. ORIC-114 is a promising therapy for NSCLC patients with atypical mutations in EGFR, including those with active CNS metastases, and is currently being evaluated in a global clinical trial (NCT05315700).
    Preclinical
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • EGFR exon 20 insertion • HER-2 exon 20 mutation
    |
    enozertinib (ORIC-114)
    over2years
    A global phase 1b study of ORIC-114, a highly selective, brain penetrant EGFR and HER2 inhibitor, in patients with advanced solid tumors harboring EGFR Exon 20 or HER2 alterations (ESMO 2023)
    Conclusions ORIC-114 has demonstrated an acceptable safety profile and preliminary antitumor activity, including in the CNS, at doses predicted to be active. Enrollment is ongoing and updated data will be presented.
    Clinical • P1 data • EGFR exon 20 • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    enozertinib (ORIC-114)
    almost3years
    Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration (clinicaltrials.gov)
    P1, N=42, Recruiting, ORIC Pharmaceuticals | Trial completion date: Dec 2023 --> Mar 2025 | Trial primary completion date: Sep 2023 --> Mar 2024
    Trial completion date • Trial primary completion date • HER2 exon 20 • Metastases
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • HER-2 overexpression • HER-2 amplification • EGFR exon 20 insertion • HER-2 exon 20 insertion • EGFR exon 20 mutation • HER-2 exon 23 mutation
    |
    enozertinib (ORIC-114)
    over3years
    Study of ORIC-114 in Patients With Advanced Solid Tumors Harboring an EGFR or HER2 Alteration (clinicaltrials.gov)
    P1, N=42, Recruiting, ORIC Pharmaceuticals
    New P1 trial
    |
    EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2)
    |
    EGFR mutation • HER-2 overexpression • HER-2 amplification • EGFR exon 20 insertion • HER-2 exon 20 insertion • EGFR exon 20 mutation • HER-2 exon 23 mutation
    |
    enozertinib (ORIC-114)