^
    Contact us  to learn more about
    our Premium Content:  News alerts, weekly reports and conference planners
    DRUG:

    inlexisertib (DCC-3116)

    i
    Other names: DCC-3116 , DCC3116, DCC 3116
    Company:
    Ono Pharmaceutical
    Drug class:
    ULK kinase inhibitor
    4ms
    A Phase 1/2 Study of Inlexisertib (DCC-3116) in Patients With RAS/MAPK Pathway Mutant Solid Tumors (clinicaltrials.gov)
    P1/2, N=144, Active, not recruiting, Deciphera Pharmaceuticals, LLC | Recruiting --> Active, not recruiting
    Enrollment closed • First-in-human
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1)
    |
    BRAF V600E • KRAS mutation • KRAS G12C • NRAS mutation • BRAF V600 • BRAF V600K • KRAS G12
    |
    Mekinist (trametinib) • Lumakras (sotorasib) • Mektovi (binimetinib) • inlexisertib (DCC-3116)
    over1year
    A Study of DCC-3116 in Combination with Anticancer Therapies in Participants with Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=94, Recruiting, Deciphera Pharmaceuticals, LLC | Trial completion date: Jun 2027 --> Mar 2029
    Trial completion date
    |
    BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    BRAF V600E • BRAF V600 • KIT mutation • KIT exon 11 mutation • PDGFRA mutation
    |
    Qinlock (ripretinib) • inlexisertib (DCC-3116)
    over1year
    Inhibition of ULK1/2 and KRASG12C controls tumor growth in preclinical models of lung cancer. (PubMed, Elife)
    Mutational activation of KRAS occurs commonly in lung carcinogenesis and, with the recent U.S. Food and Drug Administration approval of covalent inhibitors of KRASG12C such as sotorasib or adagrasib, KRAS oncoproteins are important pharmacological targets in non-small cell lung cancer (NSCLC)...Moreover, the combination of DCC-3116, a selective ULK1/2 inhibitor, plus sotorasib displays cooperative/synergistic suppression of human KRASG12C-driven lung cancer cell proliferation in vitro and superior tumor control in vivo. Additionally, in genetically engineered mouse models of KRASG12C-driven NSCLC, inhibition of either KRASG12C or ULK1/2 decreases tumor burden and increases mouse survival. Consequently, these data suggest that ULK1/2-mediated autophagy is a pharmacologically actionable cytoprotective stress response to inhibition of KRASG12C in lung cancer.
    Preclinical • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Lumakras (sotorasib) • Krazati (adagrasib) • inlexisertib (DCC-3116)
    over1year
    A Phase 1/2 Study of DCC-3116 in Patients With RAS/MAPK Pathway Mutant Solid Tumors (clinicaltrials.gov)
    P1/2, N=173, Recruiting, Deciphera Pharmaceuticals LLC | N=323 --> 173 | Trial completion date: Oct 2024 --> Aug 2028 | Trial primary completion date: Apr 2024 --> Aug 2027
    Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1)
    |
    Mekinist (trametinib) • Lumakras (sotorasib) • Mektovi (binimetinib) • inlexisertib (DCC-3116)
    over1year
    A Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=94, Recruiting, Deciphera Pharmaceuticals LLC | N=170 --> 94
    Enrollment change • Combination therapy • Metastases
    |
    BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    Qinlock (ripretinib) • inlexisertib (DCC-3116)
    over2years
    A Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=170, Recruiting, Deciphera Pharmaceuticals LLC | Not yet recruiting --> Recruiting
    Enrollment open • Combination therapy • Metastases
    |
    BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    BRAF V600E • BRAF V600 • KIT mutation • KIT exon 11 mutation • PDGFRA mutation
    |
    Erbitux (cetuximab) • Braftovi (encorafenib) • Qinlock (ripretinib) • inlexisertib (DCC-3116)
    over2years
    A Study of DCC-3116 in Combination With Anticancer Therapies in Participants With Advanced Malignancies (clinicaltrials.gov)
    P1/2, N=170, Not yet recruiting, Deciphera Pharmaceuticals LLC
    New P1/2 trial • Combination therapy • Metastases
    |
    BRAF (B-raf proto-oncogene) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)
    |
    BRAF V600E • BRAF V600 • KIT mutation • KIT exon 11 mutation • PDGFRA mutation
    |
    Erbitux (cetuximab) • Braftovi (encorafenib) • Qinlock (ripretinib) • inlexisertib (DCC-3116)
    almost3years
    DCC-3116, a first-in-class selective inhibitor of ULK1/2 kinases and autophagy, synergizes with encorafenib and cetuximab in BRAF V600E mutant colorectal cancer models (AACR 2023)
    These preclinical data demonstrate that BRAF inhibitors in combination with EGFR blockade such as E+C activate ULK-mediated autophagy as an ASR resistance mechanism which can be inhibited by DCC-3116, providing the rationale to study the combination of DCC-3116 with E+C in BRAF V600E mutated CRC patients. DCC-3116 is currently in a Phase 1 clinical trial in patients with advanced solid tumors.
    Preclinical
    |
    BRAF (B-raf proto-oncogene)
    |
    BRAF V600E • EGFR mutation • BRAF V600
    |
    Erbitux (cetuximab) • Braftovi (encorafenib) • inlexisertib (DCC-3116)
    over3years
    A Phase 1/2 Study of DCC-3116 as Monotherapy and Combination Therapy in Patients With MAPK Pathway Mutant Solid Tumors (clinicaltrials.gov)
    P1/2, N=323, Recruiting, Deciphera Pharmaceuticals LLC | Phase classification: P1 --> P1/2 | N=130 --> 323
    Phase classification • Enrollment change • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1)
    |
    BRAF V600E • KRAS mutation • KRAS G12C • NRAS mutation • BRAF V600 • BRAF V600K • NF1 mutation • KRAS G12
    |
    Mekinist (trametinib) • Lumakras (sotorasib) • Mektovi (binimetinib) • inlexisertib (DCC-3116)
    almost4years
    DCC-3116, a first-in-class selective inhibitor of ULK1/2 kinases and autophagy, synergizes with the KRASG12C inhibitor sotorasib resulting in tumor regression in KRAS mutant NSCLC xenograft models (AACR 2022)
    These data demonstrate a compelling rationale to study DCC-3116 in combination with KRASG12C inhibitors such as sotorasib in NSCLC patients. DCC-3116 is currently in a Phase 1 clinical trial in patients with advanced solid tumors with documented KRAS, NRAS or BRAF mutations (NCT04892017).
    Preclinical
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    KRAS mutation • BRAF mutation • NRAS mutation • NRAS G13
    |
    Lumakras (sotorasib) • inlexisertib (DCC-3116)
    over4years
    A Safety, Tolerability and PK Study of DCC-3116 in Patients With RAS or RAF Mutant Advanced or Metastatic Solid Tumors. (clinicaltrials.gov)
    P1, N=130, Recruiting, Deciphera Pharmaceuticals LLC | Not yet recruiting --> Recruiting
    Clinical • Enrollment open • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • BRAF V600K
    |
    Mekinist (trametinib) • inlexisertib (DCC-3116)
    almost5years
    A Safety, Tolerability and PK Study of DCC-3116 in Patients With RAS or RAF Mutant Advanced or Metastatic Solid Tumors. (clinicaltrials.gov)
    P1, N=130, Not yet recruiting, Deciphera Pharmaceuticals LLC
    Clinical • New P1 trial • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog)
    |
    BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • BRAF V600K
    |
    Mekinist (trametinib) • inlexisertib (DCC-3116)