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At the Recommended Phase II Dose (RP2D, 600 mg once daily), elisrasib monotherapy demonstrates significant efficacy across three major tumor types.
- Second-line and beyond KRAS G12C inhibitor-naïve non-small cell lung cancer (NSCLC): Objective response rate (ORR) 58.8%, median progression-free survival (mPFS) 12.2 months
- Second-line and beyond colorectal cancer (CRC): ORR 46.9%, mPFS 9.5 months
- Second-line and beyond pancreatic ductal adenocarcinoma (PDAC): ORR 65.0%, mPFS 13.5 months
Additionally, clinically meaningful efficacy was observed in NSCLC patients who were previously treated with and resistant to KRAS G12C inhibitors (ORR 32.3%, mPFS 8.1 months), along with significant antitumor activity in patients with central nervous system metastases.
ShanghaiApril 30, 2026 /PRNewswire/ — D3 Bio, a global clinical-stage biotechnology company, today announced the latest Phase II clinical data for its core asset elisrasib (D3S-001), as well as other clinical and preclinical progress in its KRAS-targeted pipeline. Elisrasib, a next-generation KRAS G12C inhibitor, demonstrates broad antitumor activity across multiple KRAS G12C-mutant solid tumors, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC), and pancreatic ductal adenocarcinoma (PDAC).
The relevant Phase II data were presented as oral presentations at the 2026 American Association for Cancer Research (AACR) Annual Meeting, including the Clinical Plenary Session (Abstract CT020) and the Clinical Trials Minisymposium (Abstract CT303), held in San Diego, California, USA.
Broad and Durable Clinical Activity Across Multiple Indications
In second-line and beyond KRAS G12C inhibitor-naïve NSCLC patients (n=68), elisrasib at the RP2D dose (600 mg once daily) showed robust efficacy, with an ORR of 58.8%, median duration of response (mDoR) of 16.5 months, and mPFS of 12.2 months.
In advanced NSCLC patients who had previously received and developed resistance to KRAS G12C inhibitors (n=31), the ORR was 32.3%, mDoR was 15.6 months, and mPFS was 8.1 months.
In previously treated colorectal cancer patients, both elisrasib monotherapy (n=32) and combination with cetuximab (n=29) showed significant efficacy: monotherapy achieved an ORR of 46.9%, mDoR of 13.1 months, and mPFS of 9.5 months; combination therapy achieved an ORR of 62.1%, mDoR of 7.0 months, and mPFS of 8.2 months. The company plans to conduct further studies to evaluate optimized combination strategies to improve the durability of response in colorectal cancer.
In advanced pancreatic ductal adenocarcinoma, elisrasib monotherapy (n=20) achieved an ORR of 65.0%, mDoR of 10.8 months, and mPFS of 13.5 months.
Favorable Safety Profile
Elisrasib was generally well tolerated in NSCLC, CRC, and PDAC patients. The incidence of Grade 3 or higher treatment-related adverse events (TRAEs) ranged from 8.7% to 15.6% across tumor types.
When combined with cetuximab, the incidence of Grade 3 TRAEs increased but was generally manageable and primarily associated with the known safety profile of cetuximab. Only one case of transient and asymptomatic Grade 4 hypokalemia was reported, with no other Grade 4 or Grade 5 TRAEs observed.
Expert Commentary
Byoung Chul Cho (MD, PhD), Professor of Medical Oncology at Yonsei Cancer Center, Yonsei University College of Medicine, South Korea, and lead investigator of this study, stated: “Even in cases where first-generation KRAS G12C inhibitors have failed, elisrasib can still induce deeper and more durable tumor responses. These results suggest that elisrasib has the potential to significantly improve treatment outcomes for patients with KRAS G12C-mutant lung cancer.”
He added: “Among patients who progressed on prior first-generation inhibitors, we identified five cases with KRAS gene amplification, an important mechanism of resistance to KRAS G12C inhibitors. In these five patients, four experienced tumor shrinkage, three achieved objective responses, and the disease control rate was 100%, further supporting the therapeutic potential of elisrasib in this specific biomarker-defined population.”
Other Presentations at AACR 2026
D3 Bio also showcased other key advancements in its KRAS pipeline, including:
- First-in-human phase 1 study of D3S-002, a purposely designed ERK1/2 inhibitor, in advanced solid tumors with MAPK pathway mutations — Poster (Abstract CT060)
- First-in-human clinical pharmacokinetic prediction of D3S-003, an orally bioavailable dual-state KRAS G12D Inhibitor — Poster (Abstract 1831)
- D3S-003: an allele-specific KRAS G12D (OFF/ON) orally available inhibitor with best-in-class potential — Poster (Abstract 4569)
Dr. Zhiqiang Chen, Founder, Chairman, and CEO of D3 Bio, stated: “The consistent and robust clinical activity of elisrasib across multiple KRAS G12C-mutant tumors further strengthens the overall momentum and capabilities of the company’s KRAS pipeline. These data indicate that elisrasib has the potential to become an important backbone therapy for KRAS G12C-mutant tumors.”
About Elisrasib (D3S-001)
Elisrasib is a next-generation KRAS G12C inhibitor designed to achieve rapid, complete, and selective target engagement. It covalently binds to the GDP-bound (OFF) conformation of KRAS G12C, effectively blocking nucleotide cycling and inhibiting oncogenic signaling pathways. Preclinical studies have demonstrated potent activity, achieving complete KRAS G12C target occupancy at clinically relevant exposure levels, along with central nervous system (CNS) penetration. Elisrasib is currently undergoing global Phase II studies as monotherapy and in combination, covering KRAS G12C-mutant solid tumors (including NSCLC, colorectal cancer (CRC), pancreatic cancer (PDAC), and others).
About D3S-002
D3S-002 is a selective ERK1/2 inhibitor designed for combination strategies, providing vertical inhibition of the MAPK pathway to enhance efficacy and overcome acquired resistance, particularly in tumors previously treated with KRAS G12C inhibitors.
Representative publication:
• Cancer Research, 2023
About D3S-003
D3S-003 is a differentiated KRAS G12D inhibitor that simultaneously targets both active (ON) and inactive (OFF) conformations, addressing one of the most common KRAS mutations. This program aims to expand the company’s multi-allele KRAS product pipeline, offering new treatment options for complex and evolving KRAS-driven tumors.
About D3 Bio
D3 Bio is a global biotechnology company focused on the discovery, development, and registration of innovative therapies with “first-in-class” or “best-in-class” potential in oncology and immune diseases. Leveraging deep clinical insights and biomarker-driven strategies, the company is advancing a pipeline targeting key oncogenic drivers and immune pathways, retaining global rights to all programs under development.
For more information, please visit: www.d3bio.com