^
    4d
    Glecirasib plus sitneprotafib in patients with KRASG12C-mutated non-small-cell lung cancer in China: an open-label, multicentre, single-arm, phase 1/2a trial. (PubMed, Lancet Respir Med)
    Glecirasib combined with sitneprotafib showed promising efficacy and manageable safety in patients with advanced KRASG12C -mutated NSCLC, particularly among those who had not received previous treatment. These findings support the evaluation of this combination in a phase 3 trial comparing this chemotherapy-free regimen to current standard of care in this patient group.
    P1/2 data • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Airuikai (glecirasib) • sitneprotafib (JAB-3312)
    7ms
    A Study of JAB-3312 in Adult Patients With Advanced Solid Tumors in China (clinicaltrials.gov)
    P1, N=17, Completed, Allist Pharmaceuticals, Inc. | Recruiting --> Completed
    Trial completion
    |
    sitneprotafib (JAB-3312)
    7ms
    JAB-3312, a Potent Allosteric SHP2 Inhibitor that Enhances the Efficacy of RTK/RAS/MAPK and PD-1 Blockade Therapies. (PubMed, Clin Cancer Res)
    JAB-3312 in combination with RTK/RAS/MAPK or PD-1 blockage therapies is a promising strategy that warrants further clinical investigation.
    Journal • PD(L)-1 Biomarker • IO biomarker
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Tagrisso (osimertinib) • Airuikai (glecirasib) • sitneprotafib (JAB-3312)
    7ms
    Glecirasib, a potent and selective covalent KRAS G12C inhibitor exhibiting synergism with cetuximab or SHP2 inhibitor JAB-3312. (PubMed, Cancer Res Commun)
    Glecirasib could effectively inhibit HRAS G12C, NRAS G12C, and several G12C-inclusive KRAS double mutants that showed resistance to adagrasib. A new drug application for glecirasib has been submitted in China, seeking approval for the treatment of non-small cell lung cancer, supported by a pivotal phase 2 single-arm study (NCT05009329). Additionally, glecirasib is being explored in clinical trials in combination with cetuximab (phase 2, NCT05194995) and JAB-3312 (phase 3, NCT06416410).
    Journal
    |
    EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • NRAS (Neuroblastoma RAS viral oncogene homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog)
    |
    KRAS wild-type • RAS wild-type • NRAS wild-type • NRAS G12
    |
    Erbitux (cetuximab) • Krazati (adagrasib) • Airuikai (glecirasib) • sitneprotafib (JAB-3312)
    8ms
    JAB-3312 Based Combination Therapy in Adult Patients With Advanced Solid Tumors (clinicaltrials.gov)
    P1/2, N=58, Completed, Allist Pharmaceuticals, Inc. | Recruiting --> Completed | N=200 --> 58
    Trial completion • Enrollment change
    |
    Keytruda (pembrolizumab) • Tagrisso (osimertinib) • Lumakras (sotorasib) • Mektovi (binimetinib) • sitneprotafib (JAB-3312)
    9ms
    JAB-21822-1006: Phase 1/2a Study of JAB-21822 Plus JAB-3312 in Patients with Advanced Solid Tumors Harboring KRAS P.G12C Mutation (clinicaltrials.gov)
    P1/2, N=240, Recruiting, Allist Pharmaceuticals, Inc. | N=124 --> 240
    Enrollment change
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Airuikai (glecirasib) • sitneprotafib (JAB-3312)
    9ms
    A Study of JAB-3312 in Adult Patients with Advanced Solid Tumors in China (clinicaltrials.gov)
    P1, N=24, Recruiting, Allist Pharmaceuticals, Inc. | Trial completion date: Dec 2023 --> Apr 2026 | Trial primary completion date: Dec 2023 --> Apr 2025
    Trial completion date • Trial primary completion date
    |
    sitneprotafib (JAB-3312)
    over1year
    JAB-21822 3002: JAB-21822 Combined With JAB-3312 Compared SOC in the First Line for Treatment of Advanced Non-small Cell Lung Cancer With KRAS p.G12C Mutation (clinicaltrials.gov)
    P3, N=392, Recruiting, Jacobio Pharmaceuticals Co., Ltd. | Not yet recruiting --> Recruiting
    Enrollment open • Metastases
    |
    carboplatin • Tevimbra (tislelizumab-jsgr) • pemetrexed • Airuikai (glecirasib) • sitneprotafib (JAB-3312)
    over1year
    Discovery of JAB-3312, a Potent SHP2 Allosteric Inhibitor for Cancer Treatment. (PubMed, J Med Chem)
    JAB-3312 was well-tolerated in animal models, and a close correlation was observed between the plasma concentration of JAB-3312 and the p-ERK inhibition in tumors. Currently, JAB-3312 is undergoing clinical trials as a potential anticancer agent.
    Journal
    |
    PD-1 (Programmed cell death 1)
    |
    sitneprotafib (JAB-3312)
    over1year
    JAB-21822 3002: JAB-21822 Combined With JAB-3312 Compared SOC in the First Line for Treatment of Advanced Non-small Cell Lung Cancer With KRAS p.G12C Mutation (clinicaltrials.gov)
    P3, N=392, Not yet recruiting, Jacobio Pharmaceuticals Co., Ltd.
    New P3 trial • Metastases
    |
    carboplatin • Tevimbra (tislelizumab-jsgr) • pemetrexed • Airuikai (glecirasib) • sitneprotafib (JAB-3312)
    almost2years
    Study to investigate JAB-3312 Combination Therapies in Adult Patients with Advanced Solid Tumors (clinicaltrialsregister.eu)
    P2, N=20, Ongoing, Jacobio Pharmaceuticals Co., Ltd.
    New P2 trial • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Lumakras (sotorasib) • sitneprotafib (JAB-3312)
    over2years
    Glecirasib (KRAS G12C inhibitor) in combination with JAB-3312 (SHP2 inhibitor) in patients with KRAS p.G12C mutated solid tumors (ESMO 2023)
    Conclusions Glecirasib plus JAB-3312 was well tolerated with promising efficacy in KRAS p.G12C NSCLC. Currently, dose expansion is underway to further evaluate efficacy and safety.
    Clinical • Combination therapy
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation
    |
    Airuikai (glecirasib) • sitneprotafib (JAB-3312)