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    DRUG:

    naporafenib (ERAS-254)

    i
    Other names: ERAS-254, LXH254, LXH 254, LXH-254
    Company:
    Erasca, Novartis
    Drug class:
    BRAF inhibitor, pan-RAF inhibitor, cRAF inhibitor
    Related drugs:
    3d
    A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2) (clinicaltrials.gov)
    P3, N=470, Recruiting, Erasca, Inc. | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    Mekinist (trametinib) • temozolomide • dacarbazine • naporafenib (ERAS-254)
    1m
    A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With NRAS-mutant Melanoma (SEACRAFT-2) (clinicaltrials.gov)
    P3, N=470, Not yet recruiting, Erasca, Inc.
    New P3 trial
    |
    Mekinist (trametinib) • temozolomide • dacarbazine • naporafenib (ERAS-254)
    3ms
    A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer (clinicaltrials.gov)
    P1, N=122, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: May 2024 --> Sep 2024 | Trial primary completion date: May 2024 --> Sep 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF mutation • BRAF V600
    |
    Mekinist (trametinib) • Tafinlar (dabrafenib) • Tevimbra (tislelizumab) • spartalizumab (PDR001) • naporafenib (ERAS-254) • batoprotafib (TNO155) • rineterkib (LTT462)
    5ms
    First-in-human study of naporafenib (LXH254) with or without spartalizumab in adult patients with advanced solid tumors harboring MAPK signaling pathway alterations. (PubMed, Eur J Cancer)
    Naporafenib, with or without spartalizumab, showed an acceptable safety profile, pharmacodynamic activity and limited antitumor activity. Additional naporafenib combination therapies are currently under investigation.
    P1 data • Journal • PD(L)-1 Biomarker • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • NRAS mutation • DUSP6 expression
    |
    spartalizumab (PDR001) • naporafenib (ERAS-254)
    6ms
    Protomer selectivity of type II RAF inhibitors within the RAS/RAF complex. (PubMed, Cell Chem Biol)
    The intracellular protomer selectivity of clinical-stage type II RAF inhibitors revealed that ARAF protomer engagement, but not engagement of BRAF or CRAF, is commensurate with inhibition of MAPK signaling in various mutant RAS cell lines. Our results support a fundamental role for ARAF in mutant RAS signaling and reveal poor ARAF protomer vulnerability for a cohort of RAF inhibitors undergoing clinical evaluation.
    Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ARAF (A-Raf Proto-Oncogene)
    |
    BRAF mutation • RAS mutation
    |
    naporafenib (ERAS-254)
    6ms
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2024 --> Apr 2024 | Trial primary completion date: Jan 2024 --> Apr 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    7ms
    A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma (clinicaltrials.gov)
    P1, N=242, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Dec 2023 --> Apr 2024 | Trial primary completion date: Dec 2023 --> Apr 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • BRAF mutation • NRAS mutation
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    10ms
    Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov)
    P1, N=105, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2024 --> Sep 2024 | Trial primary completion date: Mar 2024 --> Sep 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    Mekinist (trametinib) • gefitinib • Kisqali (ribociclib) • Tabrecta (capmatinib) • naporafenib (ERAS-254) • nazartinib (EGF816)
    10ms
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Oct 2023 --> Jan 2024
    Trial primary completion date • Metastases
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    11ms
    SEACRAFT-1: A Study to Assess Naporafenib (ERAS-254) Administered With Trametinib in Patients With RAS Q61X Mutations (clinicaltrials.gov)
    P1, N=115, Not yet recruiting, Erasca, Inc.
    New P1 trial • Metastases
    |
    RAS mutation
    |
    Mekinist (trametinib) • naporafenib (ERAS-254)
    11ms
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jul 2023 --> Oct 2023 | Trial primary completion date: May 2023 --> Oct 2023
    Trial completion date • Trial primary completion date • Metastases
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    11ms
    Structure and RAF-family kinase isoform selectivity of Type II RAF inhibitors tovorafenib and naporafenib. (PubMed, J Biol Chem)
    Selective inhibitors of BRAF (vemurafenib, dabrafenib, encorafenib) are used clinically for these indications, but they are not effective inhibitors in the context of oncogenic RAS, which drives dimerization and activation of RAF, nor for malignancies driven by aberrantly dimerized truncation/fusion variants of BRAF. Our findings have important clinical ramifications. Type II RAF inhibitors are generally regarded as Pan-RAF inhibitors, but our studies of these two agents, together with recent work with type II inhibitors belvarafenib and naporafenib, indicate that relative sparing of ARAF may be a property of multiple drugs of this class.
    Journal
    |
    BRAF (B-raf proto-oncogene) • ARAF (A-Raf Proto-Oncogene)
    |
    BRAF mutation
    |
    Zelboraf (vemurafenib) • Tafinlar (dabrafenib) • Braftovi (encorafenib) • belvarafenib (RG6185) • Ojemda (tovorafenib) • naporafenib (ERAS-254)
    12ms
    A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer (clinicaltrials.gov)
    P1, N=122, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=350 --> 122
    Enrollment closed • Enrollment change • Metastases
    |
    BRAF (B-raf proto-oncogene) • DUSP6 (Dual specificity phosphatase 6)
    |
    BRAF mutation • BRAF V600
    |
    Mekinist (trametinib) • Tafinlar (dabrafenib) • Tevimbra (tislelizumab) • spartalizumab (PDR001) • naporafenib (ERAS-254) • batoprotafib (TNO155) • rineterkib (LTT462)
    12ms
    Initial Evidence for the Efficacy of Naporafenib in Combination With Trametinib in NRAS-Mutant Melanoma: Results From the Expansion Arm of a Phase Ib, Open-Label Study. (PubMed, J Clin Oncol)
    Naporafenib plus trametinib showed promising preliminary antitumor activity in patients with NRAS-mutant melanoma. Prophylactic strategies aimed to lower the incidence of skin-related events are under investigation.
    Journal • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    KRAS mutation • BRAF mutation • NRAS mutation
    |
    Mekinist (trametinib) • naporafenib (ERAS-254)
    1year
    A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma (clinicaltrials.gov)
    P1, N=242, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2023 --> Dec 2023 | Trial primary completion date: Jun 2023 --> Dec 2023
    Trial completion date • Trial primary completion date • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • BRAF mutation • NRAS mutation
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    1year
    A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer (clinicaltrials.gov)
    P1, N=350, Recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2024 --> Apr 2024 | Trial primary completion date: Oct 2024 --> Apr 2024
    Trial completion date • Trial primary completion date • Metastases
    |
    BRAF (B-raf proto-oncogene) • DUSP6 (Dual specificity phosphatase 6)
    |
    BRAF mutation • BRAF V600
    |
    Mekinist (trametinib) • Tafinlar (dabrafenib) • Tevimbra (tislelizumab) • spartalizumab (PDR001) • naporafenib (ERAS-254) • batoprotafib (TNO155) • rineterkib (LTT462)
    1year
    Transcriptomic analysis in a renal cancer PDX model enables the deconvolution of additive and synergistic effects of six different standard of care compounds with anti-PD-1 treatment (AACR 2023)
    Several agents showed a significant increase in apoptosis induction when aPD1 was added: The largest increase was observed for the panRAF inhibitor LXH254, Sorafenib, Oxaliplatin and Doxorubicin...A more focused analysis using a subset of 19 genes described to be predictive for ICD in solid cancer confirmed the activity of LXH254 but identified Sunitinib in combination with anti PD1 as another potential inducer of ICD...Our results demonstrate that local tumor response signatures of ICD can be used to systemically identify synergistic combinations of a range of drugs with immunotherapy on a tumor specific basis. A deeper dive into the transcriptomic data will help to identify other predictive biomarker for efficacy beyond ICD.
    PD(L)-1 Biomarker • IO biomarker • Omic analysis
    |
    ICAM1 (Intercellular adhesion molecule 1) • ITGAM (Integrin, alpha M)
    |
    MHC-II expression
    |
    sorafenib • Sutent (sunitinib) • doxorubicin hydrochloride • oxaliplatin • naporafenib (ERAS-254)
    over1year
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2023 --> Jul 2023
    Trial completion date • Metastases
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    over1year
    Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations (clinicaltrials.gov)
    P1, N=142, Terminated, Novartis Pharmaceuticals | Completed --> Terminated
    Trial termination • IO biomarker • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • NRAS mutation
    |
    spartalizumab (PDR001) • naporafenib (ERAS-254)
    over1year
    Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov)
    P1, N=105, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Sep 2023 --> Mar 2024 | Trial primary completion date: Sep 2023 --> Mar 2024
    Trial completion date • Trial primary completion date • Combination therapy
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    Mekinist (trametinib) • gefitinib • Kisqali (ribociclib) • Tabrecta (capmatinib) • naporafenib (ERAS-254) • nazartinib (EGF816)
    over1year
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Aug 2022 --> Feb 2023
    Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    almost2years
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=134, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Oct 2022 --> Mar 2023
    Trial completion date
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    almost2years
    A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma (clinicaltrials.gov)
    P1, N=241, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Nov 2022 --> Apr 2023 | Trial primary completion date: Nov 2022 --> Apr 2023
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • BRAF mutation • NRAS mutation
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    almost2years
    Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov)
    P1, N=105, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Nov 2022 --> Sep 2023 | Trial primary completion date: Nov 2022 --> Sep 2023
    Trial completion date • Trial primary completion date • Combination therapy
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    Mekinist (trametinib) • gefitinib • Kisqali (ribociclib) • Tabrecta (capmatinib) • naporafenib (ERAS-254) • nazartinib (EGF816)
    almost2years
    A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer (clinicaltrials.gov)
    P1, N=350, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jun 2024 --> Oct 2024 | Trial primary completion date: Jun 2024 --> Oct 2024
    Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • DUSP6 (Dual specificity phosphatase 6)
    |
    BRAF mutation • BRAF V600
    |
    Mekinist (trametinib) • Tafinlar (dabrafenib) • Tevimbra (tislelizumab) • spartalizumab (PDR001) • naporafenib (ERAS-254) • batoprotafib (TNO155) • rineterkib (LTT462)
    almost2years
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=320, Recruiting, Novartis Pharmaceuticals | Trial completion date: Sep 2023 --> Oct 2022 | Trial primary completion date: Nov 2022 --> Aug 2022
    Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    2years
    A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer (clinicaltrials.gov)
    P1, N=350, Recruiting, Novartis Pharmaceuticals | Trial completion date: Aug 2023 --> Jun 2024 | Trial primary completion date: Aug 2023 --> Jun 2024
    Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • DUSP6 (Dual specificity phosphatase 6)
    |
    BRAF mutation • BRAF V600
    |
    Mekinist (trametinib) • Tafinlar (dabrafenib) • Tevimbra (tislelizumab) • spartalizumab (PDR001) • naporafenib (ERAS-254) • batoprotafib (TNO155) • rineterkib (LTT462)
    2years
    A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma (clinicaltrials.gov)
    P1, N=241, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting
    Enrollment closed
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • BRAF mutation • NRAS mutation
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    2years
    Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations (clinicaltrials.gov)
    P1, N=142, Completed, Novartis Pharmaceuticals | Active, not recruiting --> Completed
    Trial completion • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • NRAS mutation
    |
    spartalizumab (PDR001) • naporafenib (ERAS-254)
    2years
    A controlled drug release device facilitates the identification of favorable combinations of immune-oncology drugs with targeted or cytotoxic drugs in a patient-derived humanized mouse model of renal cancer (AACR 2022)
    Several agents showed a significant increase in apoptosis induction when nivolumab was added: The largest increase was observed for the panRAF inhibitor LXH254, Sorafenib, Oxaliplatin and Doxorubicin. Our results demonstrate that local tumor response signatures of ICD can be used to systemically identify synergistic combinations of a range of drugs with immunotherapy on a tumor specific basis. The approach may represent a new paradigm for efficient in vivo screening of novel combinations, particularly with combinations involving immunotherapies.
    Preclinical • PD(L)-1 Biomarker • IO biomarker
    |
    PTPRC (Protein Tyrosine Phosphatase Receptor Type C) • ICAM1 (Intercellular adhesion molecule 1) • ITGAM (Integrin, alpha M)
    |
    MHC-II expression
    |
    Opdivo (nivolumab) • sorafenib • doxorubicin hydrochloride • oxaliplatin • naporafenib (ERAS-254)
    over2years
    A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma (clinicaltrials.gov)
    P1, N=331, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Jan 2022 --> Nov 2022
    Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • BRAF mutation • NRAS mutation
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    over2years
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=320, Recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2023 --> Sep 2023
    Trial completion date
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    over2years
    Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations (clinicaltrials.gov)
    P1, N=142, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Nov 2021 --> Feb 2022 | Trial primary completion date: Nov 2021 --> Feb 2022
    Trial completion date • Trial primary completion date • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • NRAS mutation
    |
    spartalizumab (PDR001) • naporafenib (ERAS-254)
    over2years
    A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma (clinicaltrials.gov)
    P1, N=331, Recruiting, Novartis Pharmaceuticals | Trial completion date: May 2022 --> Nov 2022
    Clinical • Trial completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • BRAF mutation • NRAS mutation
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    over2years
    Study of Efficacy and Safety of LXH254 Combinations in Patients With Previously Treated Unresectable or Metastatic Melanoma (clinicaltrials.gov)
    P2, N=320, Recruiting, Novartis Pharmaceuticals | Trial primary completion date: Apr 2023 --> Nov 2022
    Clinical • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    NRAS mutation • BRAF V600
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)
    over2years
    Blockade of mutant RAS oncogenic signaling with a special emphasis on KRAS. (PubMed, Pharmacol Res)
    This led to the development of sotorasib as a second-line treatment of KRAS mutant non-small cell lung cancer. Considerable effort also has been expended to develop MAP kinase and PI3-kinase pathway inhibitors as indirect RAS antagonists.
    Review • Journal
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)
    |
    KRAS mutation
    |
    Lumakras (sotorasib) • Zarnestra (tipifarnib) • Krazati (adagrasib) • avutometinib (VS-6766) • pictilisib (GDC-0941) • buparlisib (AN2025) • belvarafenib (RG6185) • ulixertinib (BVD-523) • lifirafenib (BGB-283) • naporafenib (ERAS-254)
    almost3years
    Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov)
    P1, N=105, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | N=157 --> 105
    Clinical • Enrollment closed • Enrollment change • Combination therapy
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    Mekinist (trametinib) • gefitinib • Kisqali (ribociclib) • Tabrecta (capmatinib) • naporafenib (ERAS-254) • nazartinib (EGF816)
    almost3years
    Study of EGF816 in Combination With Selected Targeted Agents in EGFR-mutant NSCLC (clinicaltrials.gov)
    P1, N=157, Recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2024 --> Nov 2022 | Trial primary completion date: Mar 2024 --> Nov 2022
    Clinical • Trial completion date • Trial primary completion date • Combination therapy
    |
    EGFR (Epidermal growth factor receptor)
    |
    EGFR mutation • EGFR L858R • EGFR exon 19 deletion • EGFR T790M • EGFR exon 20 insertion • EGFR exon 20 mutation
    |
    Mekinist (trametinib) • gefitinib • Kisqali (ribociclib) • Tabrecta (capmatinib) • naporafenib (ERAS-254) • nazartinib (EGF816)
    3years
    Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations (clinicaltrials.gov)
    P1, N=142, Active, not recruiting, Novartis Pharmaceuticals | Recruiting --> Active, not recruiting | Trial completion date: Mar 2021 --> Jul 2021 | Trial primary completion date: Mar 2021 --> Jul 2021
    Clinical • Enrollment closed • Trial completion date • Trial primary completion date • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • NRAS mutation
    |
    spartalizumab (PDR001) • naporafenib (ERAS-254)
    3years
    Phase I Study of LXH254 in Patients With Advanced Solid Tumors Haboring MAPK Pathway Alterations (clinicaltrials.gov)
    P1, N=152, Recruiting, Novartis Pharmaceuticals | Active, not recruiting --> Recruiting
    Clinical • Enrollment open • IO biomarker
    |
    KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • NRAS mutation
    |
    spartalizumab (PDR001) • naporafenib (ERAS-254)
    3years
    A Study of Select Drug Combinations in Adult Patients With Advanced/Metastatic BRAF V600 Colorectal Cancer (clinicaltrials.gov)
    P1, N=395, Recruiting, Novartis Pharmaceuticals | N=280 --> 395 | Trial completion date: Feb 2023 --> Aug 2023 | Trial primary completion date: Feb 2023 --> Aug 2023
    Clinical • Enrollment change • Trial completion date • Trial primary completion date
    |
    BRAF (B-raf proto-oncogene) • DUSP6 (Dual specificity phosphatase 6)
    |
    BRAF mutation • BRAF V600
    |
    Mekinist (trametinib) • Tafinlar (dabrafenib) • spartalizumab (PDR001) • naporafenib (ERAS-254) • batoprotafib (TNO155) • rineterkib (LTT462)
    over3years
    A Phase Ib Study of LXH254-centric Combinations in NSCLC or Melanoma (clinicaltrials.gov)
    P1, N=315, Recruiting, Novartis Pharmaceuticals | Trial completion date: Jan 2022 --> May 2022
    Clinical • Trial completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • DUSP6 (Dual specificity phosphatase 6)
    |
    KRAS mutation • BRAF mutation • NRAS mutation
    |
    Mekinist (trametinib) • Kisqali (ribociclib) • naporafenib (ERAS-254) • rineterkib (LTT462)