D3S-002 / D3 Bio - LARVOL DELTA

D3 Bio Receives U.S. FDA Clearance for Two IND Applications, Enabling Phase 1 Trial of D3S‑003 and Phase 2 Combination Study of Elisrasib (D3S‑001) with D3S‑002 (PRNewswire) - "With FDA clearance received, D3 Bio will advance D3S‑003 into a Phase 1 first‑in‑human study in patients with advanced solid tumors harboring KRAS G12D mutations. The newly cleared Phase 2 study will evaluate the combination of D3S‑001 and D3S‑002 in patients with KRAS G12C–mutant non‑small cell lung cancer (NSCLC) who have progressed on prior KRAS G12C‑targeted therapies. The trial, expected to begin in the first half of 2026..."

IND • New trial • Non Small Cell Lung Cancer

A Phase 1/2 Study of D3S-002 as Monotherapy or Combination Therapy in Adult Subjects With Advanced Solid Tumors With MAPK Pathway Mutations (clinicaltrials.gov) - P1/2 | N=67 | Active, not recruiting | Sponsor: D3 Bio (Wuxi) Co., Ltd | Phase classification: P1 ➔ P1/2 | Trial completion date: Nov 2025 ➔ Apr 2028 | Trial primary completion date: Nov 2025 ➔ Apr 2028

Monotherapy • Phase classification • Trial completion date • Trial primary completion date • Solid Tumor

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