D3S-002 / D3 Bio - LARVOL DELTA

Study of D3S-002 as Monotherapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations (clinicaltrials.gov) - P1 | N=60 | Active, not recruiting | Sponsor: D3 Bio (Wuxi) Co., Ltd | Recruiting ➔ Active, not recruiting

Enrollment closed • Monotherapy • Solid Tumor

Concurrent inhibition of KRAS G12C and ERK1/2 overcomes acquired resistance to KRAS G12C inhibitors (G12Cis) conferred by various genetic alterations (EORTC-NCI-AACR 2024) - "Here we sought to investigate the efficacy of D3S-002 in combination with D3S-001 or other G12Cis in overcoming acquired resistance to KRAS G12C-targeted therapies in human cancers.Material and G12Ci acquired resistant models with various clinically relevant genetic alterations were utilized, including the colorectal cancer (CRC) patient-derived xenograft (PDX) model CR9537 which harbors an acquired secondary KRAS Q61H mutation, and the pancreatic cancer cell line-derived xenograft (CDX) model AMG510-R-xMIAPaCa-2 with acquired KRAS gene amplification. The combination of the ERK1/2 kinase inhibitor D3S-002 with G12Ci demonstrated the potential to overcome acquired resistance to G12Ci contributed by various genetic resistance mechanisms observed in the clinic. Results from this study provide a compelling rationale for further investigation of the combination strategy of D3S-002 and a G12Ci in patients who have relapsed on KRAS G12C-targeted therapies."

Preclinical • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

Study of D3S-002 as Monotherapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations (clinicaltrials.gov) - P1 | N=60 | Recruiting | Sponsor: D3 Bio (Wuxi) Co., Ltd | Not yet recruiting ➔ Recruiting

Enrollment open • Metastases • Monotherapy • Oncology • Solid Tumor

Study of D3S-002 as Monotherapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations (clinicaltrials.gov) - P1 | N=60 | Not yet recruiting | Sponsor: D3 Bio (Wuxi) Co., Ltd

Metastases • Monotherapy • New P1 trial • Oncology • Solid Tumor

Vertical inhibition of the MAPK pathway with D3S-002, a potent and selective ERK1/2 inhibitor, to improve anti-tumor activity of and overcome resistance to KRAS G12C inhibitors (AACR 2023) - "In NCI-H358 NSCLC and SW837 CRC models that are sensitive to KRAS G12C inhibitor monotherapy, adding D3S-002 to D3S-001 or to D3S-001 and cetuximab doublet regimen led to faster, deeper, and more durable anti-tumor responses at dose levels that are well tolerated in mice with no body weight loss observed. Adding D3S-002 to D3S-001 or MRTX849 resulted in over 80% tumor growth inhibition and significantly prolonged survival, suggesting the combination treatment can be beneficial for KRAS G12C inhibitor pre-treated patient population.Collectively, vertical inhibition by concurrently targeting KRAS G12C and ERK1/2 with respective inhibitor D3S-001 and D3S-002 demonstrated enhanced anti-tumor activity in NSCLC and CRC models with different sensitivity to KRAS G12C inhibitor monotherapy. These results provide a strong rationale for further investigation of the combination strategy of D3S-001 and D3S-002 in KRAS G12C-mutant solid tumors in the clinic."

Colorectal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS