^
    3ms
    Exploratory ctDNA analyses from first-in-human phase I trial of D3S-001 in patients with advanced solid tumor harboring a KRAS G12C mutation (ESMO Asia 2024)
    Conclusions Rapid and sustained molecular response correlated with clinical efficacy and highlighted the importance of TE kinetics of D3S-001. Our data shows that b G12C pos and 100% G12C clearance were associated with better treatment outcome.
    Clinical • P1 data • Circulating tumor DNA • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MAP2K1 (Mitogen-activated protein kinase kinase 1)
    |
    KRAS mutation • KRAS G12C • KRAS G12D • STK11 mutation • KRAS G12 • KRAS Q61H
    |
    Guardant360® CDx
    |
    D3S-001
    8ms
    D3S-001, a KRAS G12C inhibitor with rapid target engagement kinetics, overcomes nucleotide cycling and demonstrates robust preclinical and clinical activities. (PubMed, Cancer Discov)
    In the presence of growth factors, such as EGF and HGF, the ability of sotorasib and adagrasib to inhibit KRAS was compromised whereas the TE kinetics of D3S-001 was nearly unaffected, a unique feature differentiating D3S-001 from other GDP-bound G12C inhibitors. Furthermore, the high covalent potency and cellular TE efficiency of D3S-001 contributed to robust anti-tumor activity preclinically and translated into promising clinical activity in an ongoing phase 1 trial (NCT05410145).
    Preclinical • Journal
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    Lumakras (sotorasib) • Krazati (adagrasib) • D3S-001
    9ms
    A Study of D3S 001 Monotherapy or Combination Therapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation (clinicaltrials.gov)
    P1/2, N=352, Recruiting, D3 Bio (Wuxi) Co., Ltd | Phase classification: P1 --> P1/2 | N=168 --> 352 | Trial completion date: May 2025 --> Sep 2026 | Trial primary completion date: May 2025 --> Sep 2026
    Phase classification • Enrollment change • Trial completion date • Trial primary completion date • Combination therapy • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    Keytruda (pembrolizumab) • Erbitux (cetuximab) • cisplatin • carboplatin • pemetrexed • D3S-001
    1year
    A Study of D3S-001 as Monotherapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation (clinicaltrials.gov)
    P1, N=168, Recruiting, D3 Bio (Wuxi) Co., Ltd
    Trial completion date • Trial primary completion date • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    D3S-001
    almost2years
    A Study of D3S-001 as Monotherapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation (clinicaltrials.gov)
    P1, N=168, Recruiting, D3 Bio (Wuxi) Co., Ltd | N=98 --> 168
    Enrollment change • Metastases
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    D3S-001
    over2years
    A Study of D3S-001 as Monotherapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation (clinicaltrials.gov)
    P1, N=98, Recruiting, D3 Bio (Wuxi) Co., Ltd | Not yet recruiting --> Recruiting
    Enrollment open
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    D3S-001
    over2years
    A Study of D3S-001 as Monotherapy in Subjects With Advanced Solid Tumors With a KRAS p.G12C Mutation (clinicaltrials.gov)
    P1, N=98, Not yet recruiting, D3 Bio (Wuxi) Co., Ltd
    New P1 trial
    |
    KRAS (KRAS proto-oncogene GTPase)
    |
    KRAS mutation • KRAS G12C • KRAS G12
    |
    D3S-001