^
    1m
    Allosteric SHP2 inhibitors suppress lung cancer cell migration by inhibiting non-canonical activation of EphA2 via the ERK-RSK signaling pathway. (PubMed, Sci Rep)
    We herein demonstrated that the allosteric SHP2 inhibitors, SHP099 and TNO155, suppressed both the TNF-α- and growth factor-induced non-canonical phosphorylation of EphA2 at Ser-897 via the ERK-RSK pathway. In contrast, these inhibitors did not affect the signaling pathways leading to EphA2 induced by TPA in HeLa cells or by TNF-α in A549 cells, indicating the involvement of a complex signaling network in these processes. Collectively, the present results highlight the potential of allosteric SHP2 inhibitors as agents targeting the non-canonical activation of EphA2 in LUAD cells.
    Journal
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    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • EML4 (EMAP Like 4) • TNFA (Tumor Necrosis Factor-Alpha)
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    KRAS mutation • EGFR exon 19 deletion • ALK rearrangement
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    SHP099 • batoprotafib (TNO155)
    1m
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1, N=610, Active, not recruiting, Amgen | Recruiting --> Active, not recruiting | N=1200 --> 610 | Trial primary completion date: Jun 2026 --> Dec 2026
    Enrollment closed • Enrollment change • Trial primary completion date
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    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    3ms
    RAS pathway inhibitors combined with targeted agents are active in patient-derived spheroids with oncogenic KRAS variants from multiple cancer types. (PubMed, Cancer Res Commun)
    Vertical inhibition of the RAS/MEK/ERK pathway by targeting SHP2 or SOS1 and the downstream kinases MEK (trametinib) or ERK (temuterkib) was highly effective. Inhibition of upstream tyrosine receptor kinases with nintedanib in combination with batoprotafib or BI-3406 was also effective, and in combination with sotorasib, demonstrated synergy in spheroids harboring KRAS G12C. Dual inhibition of the RAS/MEK/ERK and PI3K/AKT/mTOR pathways by batoprotafib or sotorasib with either the mTORC1/2 inhibitor sapanisertib or the AKT inhibitor ipatasertib demonstrated combination activity, primarily in spheroids harboring KRAS G12C. The BCL-2 inhibitor venetoclax in combination with sotorasib, batoprotafib or BI-3406 resulted in additive and synergistic cytotoxicity. Lastly, concurrent inhibition of the KRAS pathway with sotorasib and batoprotafib demonstrated combination activity in spheroids containing KRAS G12C.
    Journal
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    KRAS (KRAS proto-oncogene GTPase)
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    KRAS G12C
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    Venclexta (venetoclax) • Mekinist (trametinib) • Lumakras (sotorasib) • sapanisertib (CB-228) • ipatasertib (RG7440) • nintedanib • BI-3406 • batoprotafib (TNO155) • temuterkib (LY3214996)
    3ms
    Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=227, Terminated, Novartis Pharmaceuticals | Active, not recruiting --> Terminated; Business reasons and not due to any safety concerns
    Trial termination
    |
    KRAS (KRAS proto-oncogene GTPase) • DUSP6 (Dual specificity phosphatase 6)
    |
    batoprotafib (TNO155) • nazartinib (EGF816)
    5ms
    Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=227, Active, not recruiting, Novartis Pharmaceuticals | Trial primary completion date: Nov 2025 --> Jul 2025 | Trial completion date: Nov 2025 --> Jul 2025
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase) • DUSP6 (Dual specificity phosphatase 6)
    |
    batoprotafib (TNO155) • nazartinib (EGF816)
    8ms
    KRYSTAL-2: Adagrasib in Combination With TNO155 in Patients With Cancer (KRYSTAL 2) (clinicaltrials.gov)
    P1, N=86, Completed, Mirati Therapeutics Inc. | Active, not recruiting --> Completed
    Trial completion
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Krazati (adagrasib) • batoprotafib (TNO155)
    9ms
    KontRASt-01: Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov)
    P1/2, N=344, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Apr 2026 --> Aug 2026 | Trial primary completion date: Apr 2026 --> Aug 2026
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Tevimbra (tislelizumab-jsgr) • batoprotafib (TNO155) • opnurasib (JDQ443)
    9ms
    CodeBreak101: Sotorasib Activity in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation (CodeBreak 101) (clinicaltrials.gov)
    P1, N=1200, Recruiting, Amgen | Trial completion date: Mar 2028 --> Dec 2027
    Trial completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Mekinist (trametinib) • Tecentriq (atezolizumab) • Gilotrif (afatinib) • Ibrance (palbociclib) • carboplatin • paclitaxel • docetaxel • everolimus • Vectibix (panitumumab) • Lumakras (sotorasib) • pemetrexed • oxaliplatin • irinotecan • batoprotafib (TNO155) • vociprotafib (RMC-4630) • BI 1701963 • zeluvalimab (AMG 404)
    9ms
    Dose Finding Study of TNO155 in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1, N=227, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: May 2025 --> Nov 2025 | Trial primary completion date: May 2025 --> Nov 2025
    Trial completion date • Trial primary completion date
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    batoprotafib (TNO155) • nazartinib (EGF816)
    12ms
    KontRASt-01: Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov)
    P1/2, N=344, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Aug 2025 --> Apr 2026 | Trial primary completion date: Aug 2025 --> Apr 2026
    Trial completion date • Trial primary completion date • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Tevimbra (tislelizumab-jsgr) • batoprotafib (TNO155) • opnurasib (JDQ443)
    12ms
    KontRASt-01: Study of JDQ443 in Patients With Advanced Solid Tumors Harboring the KRAS G12C Mutation (clinicaltrials.gov)
    P1/2, N=344, Active, not recruiting, Novartis Pharmaceuticals | Trial completion date: Mar 2026 --> Aug 2025 | Trial primary completion date: Mar 2026 --> Aug 2025
    Trial completion date • Trial primary completion date • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Tevimbra (tislelizumab-jsgr) • batoprotafib (TNO155) • opnurasib (JDQ443)
    1year
    Discovery of novel phenyl urea SHP2 inhibitors with anti-colon cancer and potential immunomodulatory effects. (PubMed, Eur J Med Chem)
    Currently, no SHP2 inhibitors have been approved for clinical use, and colorectal cancer (CRC) cells exhibited frequent resistance to reported SHP2 inhibitors, such as SHP099 and TNO155. A8 significantly suppressed in vivo tumor growth in a CT26 mouse model and activated immunomodulatory effects in tumor microenvironment. Our work demonstrated that A8 has the potential to be a lead compound for the further development of SHP2 inhibitor and the treatment of CRC.
    Journal • Immunomodulating
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    PD-L1 (Programmed death ligand 1)
    |
    SHP099 • batoprotafib (TNO155)