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    DRUG CLASS:

    ERK1 inhibitor

    Related drugs:
    1d
    The SHERPA trial: A phase I study combining SHP2 inhibitor RMC-4630 and ERK inhibitor LY3214996 in patients with KRAS-mutant pancreatic, non-small cell lung and colorectal cancer. (PubMed, Eur J Cancer)
    Sufficient exposure to RMC-4630 and LY3214996 was not reached due to the toxicity profile of the combination. Tumor response was not demonstrated at the explored dose levels. Therefore, the dose escalation was discontinued, and the RP2D was not determined.
    P1 data • Journal
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    KRAS (KRAS proto-oncogene GTPase)
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    KRAS mutation
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    vociprotafib (RMC-4630) • temuterkib (LY3214996)
    19d
    Ulixertinib in Treating Patients With Advanced Solid Tumors, Non-Hodgkin Lymphoma, or Histiocytic Disorders With MAPK Pathway Mutations (A Pediatric MATCH Treatment Trial) (clinicaltrials.gov)
    P2, N=20, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Mar 2026 --> Mar 2027
    Trial completion date
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    ulixertinib (BVD-523)
    2ms
    HERKULES-3: A Study of ERAS-007 in Patients With Advanced Gastrointestinal Malignancies (clinicaltrials.gov)
    P1/2, N=101, Completed, Erasca, Inc. | Active, not recruiting --> Completed
    Trial completion
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
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    BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600
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    Erbitux (cetuximab) • Ibrance (palbociclib) • Braftovi (encorafenib) • ERAS-007
    2ms
    ERK1/2-targeted Cancer therapies: Recent advances, potential drug resistance, and applicability analysis of emerging technologies. (PubMed, Bioorg Chem)
    Firstly, although first-generation ATP-competitive inhibitors such as Ulixertinib have shown antitumor activity in early-phase trials, their efficacy varies widely across patient populations and is often accompanied by mechanism-based toxicities (including rash and diarrhea), highlighting a substantial disconnection between preclinical predictions and clinical outcomes...Furthermore, it highlights emerging technological advances, including innovative modalities that address limitations of traditional ATP-competitive inhibitors, such as targeted protein degradation (TPD) approaches. Collectively, this review seeks to outline a clearer roadmap toward realizing the full therapeutic potential of ERK1/2-targeted interventions in cancer treatment.
    Review • Journal
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    MAPK1 (Mitogen-activated protein kinase 1)
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    ulixertinib (BVD-523)
    2ms
    LY3214996 Plus Abemaciclib in Recurrent Glioblastoma Patients (clinicaltrials.gov)
    P1, N=42, Completed, Nader Sanai | Active, not recruiting --> Completed | Trial completion date: Feb 2028 --> Sep 2025
    Trial completion • Trial completion date
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    CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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    Verzenio (abemaciclib) • temuterkib (LY3214996)
    2ms
    A Study to Evaluate Safety, PK and Efficacy of GH55 in Combination With GH21 in Patients With Solid Tumors (clinicaltrials.gov)
    P1/2, N=152, Not yet recruiting, Suzhou Genhouse Bio Co., Ltd.
    New P1/2 trial
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    HBI-2376
    3ms
    A Phase II Study of BVD-523 in Metastatic Uveal Melanoma (clinicaltrials.gov)
    P2, N=13, Terminated, Dana-Farber Cancer Institute | Active, not recruiting --> Terminated; This was a Simon two stage design trial that terminated after the first stage due to lack of response.
    Trial termination
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    DUSP6 (Dual specificity phosphatase 6)
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    ulixertinib (BVD-523)
    3ms
    Discovery of Novel and Potent Dual PARP1/ERK Inhibitors as a Promising Strategy for Cancer Therapy. (PubMed, J Med Chem)
    In an HCT116 xenograft model, I-16 (20 mg/kg) elicited significant tumor growth suppression, outperforming Olaparib (50 mg/kg) or BVD-523 (5 mg/kg) monotherapy and achieving efficacy comparable to their combination. These findings suggest that I-16, as the first potent dual PARP1/ERK inhibitor, represents a promising candidate for cancer therapy.
    Journal • BRCA Biomarker • PARP Biomarker
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    BRCA (Breast cancer early onset)
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    BRCA wild-type • BRCA mutation
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    Lynparza (olaparib) • ulixertinib (BVD-523)
    3ms
    Window-of-Opportunity Trial of Ulixertinib for MAPK-Activated Gliomas (clinicaltrials.gov)
    P1, N=40, Recruiting, M.D. Anderson Cancer Center | N=20 --> 40
    Enrollment change
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    FGFR (Fibroblast Growth Factor Receptor) • PTPN11 (Protein Tyrosine Phosphatase Non-Receptor Type 11)
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    ulixertinib (BVD-523)
    5ms
    Window-of-Opportunity Trial of Ulixertinib for MAPK-Activated Gliomas (clinicaltrials.gov)
    P1, N=20, Recruiting, M.D. Anderson Cancer Center | Trial primary completion date: Sep 2025 --> Sep 2027
    Trial primary completion date
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    NF1 (Neurofibromin 1)
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    ulixertinib (BVD-523)
    5ms
    LY3214996 and Cetuximab Alone or in Combination With Abemaciclib for the Treatment of Unresectable or Metastatic Colorectal Cancer (clinicaltrials.gov)
    P1/2, N=46, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2028 | Trial primary completion date: Dec 2025 --> Dec 2028
    Trial completion date • Trial primary completion date
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    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
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    Erbitux (cetuximab) • Verzenio (abemaciclib) • temuterkib (LY3214996)
    5ms
    A Phase 1/2 Study of D3S-002 as Monotherapy or Combination Therapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations (clinicaltrials.gov)
    P1/2, N=67, Active, not recruiting, D3 Bio (Wuxi) Co., Ltd | Phase classification: P1 --> P1/2 | Trial completion date: Nov 2025 --> Apr 2028 | Trial primary completion date: Nov 2025 --> Apr 2028
    Phase classification • Trial completion date • Trial primary completion date
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    D3S-002 • elisrasib (D3S-001)