D3S-001 / D3 Bio - LARVOL DELTA

D3 Bio, Inc. Announces FDA…Orphan Drug Designation for D3S-001 for the Treatment of Patients with KRAS G12C-Mutated Cancers (PRNewswire) - "Orphan Drug Designation was granted for treatment of colorectal cancer (CRC) harboring KRAS G12C mutant protein....Orphan Drug Designations are based on clinical data from an ongoing Phase 1/2 study (NCT05410145)..."

Orphan drug • Colorectal Cancer

A Phase 1 Study to Assess Food Effect on the Pharmacokinetics of D3S-001 in Healthy Adult Participants (clinicaltrials.gov) - P1 | N=14 | Recruiting | Sponsor: D3 Bio (Wuxi) Co., Ltd

New P1 trial

D3 Bio, Inc. Announces FDA Breakthrough Therapy Designation…for D3S-001 for the Treatment of Patients with KRAS G12C-Mutated Cancers (PRNewswire) - "Breakthrough Therapy Designation was granted for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC) who have had prior treatment with platinum-based chemotherapy and anti-PD-(L)1 antibody but have not been previously treated with a KRAS G12C inhibitor...The Breakthrough Therapy....based on clinical data from an ongoing Phase 1/2 study (NCT05410145)..."

Breakthrough therapy • Evidence highlight • Non Small Cell Lung Cancer • KRAS

D3S-001-100: 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=442 | Recruiting | Sponsor: D3 Bio (Wuxi) Co., Ltd | Trial completion date: Sep 2026 ➔ Feb 2027 | Trial primary completion date: Sep 2026 ➔ Feb 2027

Monotherapy • Trial completion date • Trial primary completion date • Solid Tumor • KRAS

D3S-001, a next generation GDP-bound KRAS G12C inhibitor, as monotherapy in KRAS G12C inhibitor resistant non-small cell lung cancer (AACR 2025) - P1/2 | "In pre-clinical studies, D3S-001 resulted in tumor regression in xenograft models that are resistant to sotorasib (soto) and adagrasib (ada). These findings highlight the potential of D3S-001 to overcome the limitations of earlier KRAS G12Ci and address unmet needs in G12Ci resistant NSCLC, offering a promising therapeutic option for pts with KRAS G12C-mutant cancers."

Monotherapy • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • BRAF • CDKN2A • EGFR • KRAS • MYC • NTRK1 • NTRK2 • NTRK3 • PIK3CG • TP53

Yonsei Cancer Center present positive P1 results for next-gen KRAS G12C inhibitor treatment (Korea Biomedical Review) - P1/2 | N=392 | NCT05410145 | Sponsor: D3 Bio (Wuxi) Co., Ltd | "A research team at Yonsei Cancer Center found that D3S-001, a new KRAS G12C-targeting therapy being developed by D3 Bio, a Chinese biotech, has demonstrated a promising objective response rate of 73.5 percent in a phase 1 trial involving patients with advanced solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer, and pancreatic cancer....The overall objective response rate was 73.5 percent, with responses observed in 66.7 percent of NSCLC patients, 88.9 percent of colorectal cancer patients, and 75 percent of pancreatic cancer patients....Among 20 NSCLC patients who had shown no benefit from prior therapies, 60 percent experienced tumor shrinkage, and the response rate was 30 percent."

P1 data • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

Next-generation KRAS-G12C inhibitor D3S-001 shows promise. (PubMed, Nat Rev Clin Oncol) - No abstract available

Journal • KRAS

AACR 2025 Data Highlights the Activity of D3S-001 in Overcoming Resistance in Patients with NSCLC Who Have Progressed on First-Generation G12C Inhibitors (Businesswire) - P1/2 | N=392 | NCT05410145 | Sponsor: D3 Bio (Wuxi) Co., Ltd | "At AACR 2025, D3 Bio shared updated results from a Phase 2 expansion cohort of NSCLC patients who had previously been treated with FDA-approved or other experimental G12C inhibitors. The compound demonstrates encouraging clinical benefits in this patient population. The data include: 60% of patients experienced tumor shrinkage; 30% achieved partial responses; 80% disease control rate; 11 of 14 ctDNA-positive patients achieved >90% G12C MAF reduction, with 6 achieving partial response (a 43% response rate in the ctDNA-positive population); Responses were observed in patients with KRAS G12C amplification, a known resistance mechanism to first-generation inhibitors, consistent with previous preclinical observations."

P2 data • Non Small Cell Lung Cancer

D3 Bio Announces Nature Medicine Publication and AACR 2025 Presentation Highlighting D3S-001 as a Next-Generation KRAS G12C Inhibitor with Best-in-Class Potential (Businesswire) - P1/2 | N=392 | NCT05410145 | Sponsor: D3 Bio (Wuxi) Co., Ltd | "D3 Bio Announces Nature Medicine Publication and AACR 2025 Presentation Highlighting D3S-001 as a Next-Generation KRAS G12C Inhibitor with Best-in-Class Potential....In a Phase 1a/1b clinical study (NCT05410145), D3S-001 demonstrated an overall objective response rate (ORR) of 73.5% in KRAS G12C inhibitor-naïve patients across multiple tumor types, including: 66.7% in non–small cell lung cancer (NSCLC); 88.9% in colorectal cancer (CRC); 75.0% in pancreatic ductal adenocarcinoma (PDAC). Additionally, in 20 patients with NSCLC who had previously been treated with and progressed on first-generation G12C inhibitors, including sotorasib and adagrasib, D3S-001 achieved a 30.0% overall response rate (ORR) and 80.0% disease control rate (DCR), providing direct clinical evidence of its ability to overcome acquired resistance to first-generation G12Ci therapies."

P1 data • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Ductal Adenocarcinoma

D3S-001 in advanced solid tumors with KRASG12C mutations: a phase 1 trial. (PubMed, Nat Med) - P1/2 | "The phase 1b expansion phase is ongoing. ClinicalTrials.gov identifier: NCT05410145 ."

Journal • P1 data • Colorectal Cancer • Hepatology • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • KRAS

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) - P1/2 | "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."

Circulating tumor DNA • Clinical • Metastases • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • CDKN2A • KRAS • MAP2K1 • STK11

D3 Bio’s D3S-001 Demonstrates Significantly Improved Covalent Potency in Depleting Cellular Active KRAS in…Clinical Studies in KRAS G12C-Mediated Cancers (Businesswire) - P1/2 | N=392 | NCT05410145 | Sponsor: D3 Bio (Wuxi) Co., Ltd | "Citing the ongoing D3S-001 Phase 1/2 trial in KRAS G12C-mediated solid tumors, the study noted that durable RECIST responses were observed across all dose cohorts, as well as systemic and intracranial anti-tumor activity in two highlighted patients with non-small cell lung cancer (NSCLC) enrolled in the first dose cohort of this trial...Results from the Phase 1a dose-escalation study...showed favorable tolerability across different dose levels...D3S-001 demonstrated consistent and promising efficacy in the G12C-inhibitor naïve population, with a confirmed overall response rate (ORR) of 73.5% across tumor types....Expansion study cohorts are ongoing and focus on monotherapy and combination therapy regimens in non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and pancreatic ductal adenocarcinoma (PDAC)....'We are excited with the progress of D3S-001....expect to report topline Phase 2 data in 2025.'"

P1 data • P2 data • Trial status • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • Thoracic Cancer

D3 Bio’s D3S-001 Demonstrates Significantly Improved Covalent Potency in Depleting Cellular Active KRAS in Pre-Clinical…in KRAS G12C-Mediated Cancers (Businesswire) - "D3 Bio...announced that its lead compound, a next-generation KRAS G12C inhibitor, D3S-001, demonstrated rapid target engagement, overcame the limiting factors of nucleotide cycling and RTK activation, and showed robust preclinical...activities in KRAS G12C-mediated cancers, in a study published in Cancer Discovery...D3S-001 demonstrated substantially improved covalent potency and better and faster target engagement (TE) kinetics, compared to the approved drugs (sotorasib and adagrasib) in the class. This suggests that D3S-001 has the potential to 'lock' KRAS G12C in its inactive (GDP-bound) state more efficiently, possibly resulting in cellular active KRAS depletion in clinically relevant doses....In cell line and patient-derived tumor xenograft models across multiple cancer types, D3S-001 demonstrated significantly more robust anti-tumor responses than the other KRAS G12C inhibitors in the study."

Preclinical • Oncology • 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

D3 Bio’s D3S-001 Demonstrates Significantly Improved Covalent Potency in Depleting Cellular Active KRAS in Pre-Clinical…Studies in KRAS G12C-Mediated Cancers (Businesswire) - "D3S-001 Demonstrated Significantly Improved Covalency and Rapid Target Engagement Not Affected by Growth Factors, Potentially Depleting Cellular Active KRAS in Multiple Preclinical Models...In cell line and patient-derived tumor xenograft models across multiple cancer types, D3S-001 demonstrated significantly more robust anti-tumor responses than the other KRAS G12C inhibitors in the study. Importantly, these include a delay in disease progression in tumors that were resistant to an FDA-approved KRAS G12C inhibitor. D3S-001 also exhibited brain penetration properties, resulting in durable intracranial tumor regression in mouse models with brain metastases."

Preclinical • Brain Cancer • Oncology • Solid Tumor

D3 Bio’s D3S-001 Demonstrates Significantly Improved Covalent Potency in Depleting Cellular Active KRAS in...Clinical Studies in KRAS G12C-Mediated Cancers (Businesswire) - P1/2 | N=392 | NCT05410145 | Sponsor: D3 Bio (Wuxi) Co., Ltd | "Correlates to Anti-tumor Activity Preclinically, Clinically Meaningful Response Observed in Phase 1 Trial in KRAS G12C-mediated cancers....Citing the ongoing D3S-001 Phase 1/2 trial in KRAS G12C-mediated solid tumors, the study noted that durable RECIST responses were observed across all dose cohorts, as well as systemic and intracranial anti-tumor activity in two highlighted patients with non-small cell lung cancer (NSCLC) enrolled in the first dose cohort of this trial."

P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Phase I/II study of D3S-001, a second generation KRAS G12C inhibitor in advanced/metastatic solid tumors with KRAS G12C mutations (ESMO 2024) - P1/2 | "D3S-001, a 2G G12Ci, demonstrated favorable tolerability and consistent promising efficacy across KRAS G12C-mutated NSCLC, CRC, and PDAC."

Metastases • P1/2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KRAS

Yonsei releases promising P1 results of KRAS G12C-targeted therapy for NSCLC (Korea Biomedical Review) - P1/2 | N=352 | NCT05410145 | Sponsor: D3 Bio (Wuxi) Co., Ltd | "The phase 1 trial of D3S-001, conducted by Professors Cho Byoung-chul, Lim Sun-min, and Yu Mi-ra at the hospital, involved 25 NSCLC patients, four pancreatic cancer patients, and 12 colorectal cancer patients. The results showed an objective response rate of 70 percent for NSCLC, 100 percent for pancreatic cancer, and 78 percent for colorectal cancer. The team also found that the response duration was longer than that of existing therapies....Preclinical trials conducted by the same research team on animal models also yielded promising results. The studies involved transplanting tumors from KRAS G12C-mutant NSCLC patients and sotorasib-resistant patients into mice. The new therapy demonstrated superior efficacy, including a reduction in brain metastases."

P1 data • Preclinical • Colorectal Cancer • Non Small Cell Lung Cancer • Pancreatic Cancer

D3S-001, a KRAS G12C inhibitor with rapid target engagement kinetics, overcomes nucleotide cycling and demonstrates robust preclinical and clinical activities. (PubMed, Cancer Discov) - P1/2 | "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)."

Journal • Preclinical • Oncology • KRAS

D3S-001, a second-generation GDP-bound KRAS G12C inhibitor, overcomes nucleotide cycling and demonstrates robust preclinical and clinical activities (AACR 2024) - P1/2 | "First-generation KRAS G12C inhibitors [G12Ci(s)], such as sotorasib and adagrasib, are limited by the depth and duration of clinical responses. Response rate and duration are reported in a companion clinical trial abstract submitted to this AACR meeting.In conclusion, D3S-001 is a second-generation GDP-bound KRAS G12Ci that overcomes GDP-to-GTP cycling. Its high covalent efficiency and rapid TE kinetics correlated with robust anti-tumor activity preclinically and translated into promising clinical activity with a high response rate and durable responses in a phase 1 trial."

Preclinical • Oncology • Solid Tumor • KRAS

A phase 1 study of D3S-001, a second-generation GDP-bound KRAS G12C inhibitor, as monotherapy in patients with KRAS G12C-mutated solid tumors (AACR 2024) - P1/2 | "D3S-001, a 2G G12Ci, is well tolerated and delivers promising anti-tumor activity in pts with NSCLC, CRC, and PDAC carrying KRAS G12C mutation across all dose levels in FIH trial."

Clinical • Monotherapy • P1 data • Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pancreatic Cancer • Solid Tumor • KRAS

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 | Sponsor: 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

Combination therapy • Enrollment change • Metastases • Monotherapy • Phase classification • Trial completion date • Trial primary completion date • Oncology • Solid Tumor • KRAS

D3 Bio Completes Series A+ Round to Advance Innovative Oncology Pipeline (PRNewswire) - "D3 Bio...announces its closing of Series A+ financing round led by Medicxi, a leading European life sciences investment firm. D3 Bio's existing investors, Matrix Partners China and WuXi AppTec's Corporate Venture Fund also participated. The substantial investment of US$62M in this round underscores D3 Bio's steadfast commitment to advancing its pioneering oncology pipeline. The funding will be allocated to expedite the development of D3 Bio's assets through preclinical and clinical stages, with a particular focus on accelerating the global clinical trial of D3S-001, a new generation small molecule KRAS G12C inhibitor with the best-in-class potential."

Financing • Solid Tumor

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 | Sponsor: D3 Bio (Wuxi) Co., Ltd

Trial completion date • Oncology • Solid Tumor • KRAS

Combination of D3L-002, an anti-TIGIT/PVRIG bispecific antibody, with D3S-001, a KRAS G12C inhibitor, transformed tumor microenvironment from "cold" to "hot" and achieved durable tumor remission in preclinical models. (AACR-NCI-EORTC 2023) - No abstract available

Preclinical • Tumor microenvironment • Oncology • KRAS • TIGIT