Elisrasib monotherapy demonstrates notable efficacy in three major tumor types at its recommended phase 2 dose (RP2D, 600 mg QD). Phase 2 clinical outcomes include:

• 2L+ KRAS G12Ci–naïve NSCLC: ORR of 58.8%, mPFS of 12.2 months
• 2L+ colorectal cancer (CRC): ORR of 46.9%, mPFS of 9.5 months
• 2L+ pancreatic ductal adenocarcinoma (PDAC): ORR of 65.0%, mPFS of 13.5 months

Additionally, meaningful efficacy was observed in KRAS G12C inhibitor-pretreated and refractory NSCLC, with an ORR of 32.3% and mPFS of 8.1 months, and significant activity in patients with CNS metastases.

, /PRNewswire/ -- D3 Bio Inc., a global clinical-stage biotechnology company dedicated to developing innovative oncology therapeutics, today announced new phase 2 clinical data from its lead asset elisrasib (D3S-001), a next-generation KRAS G12C inhibitor, alongside additional clinical and preclinical results from its KRAS-focused pipeline. The phase 2 studies demonstrate that elisrasib delivers broad antitumor activity across multiple KRAS G12C-mutant solid tumors, including NSCLC, CRC, and PDAC.

Phase 2 data for elisrasib were shared as oral presentations at the American Association for Cancer Research (AACR) Annual Meeting 2026 during both the Clinical Plenary Session (Abstract CT020) and the Clinical Trials Mini-Symposium (Abstract CT303) in San Diego, CA.

Extensive and Durable Clinical Activity Observed Across Indications

In 2L+ KRAS G12Ci-naïve NSCLC (n=68), elisrasib demonstrated robust efficacy at the RP2D (600 mg QD) with an ORR of 58.8%, median duration of response (mDoR) of 16.5 months, and mPFS of 12.2 months. Among late-line NSCLC patients refractory to prior KRAS G12C inhibitor therapy (n=31), an ORR of 32.3%, mDoR of 15.6 months, and mPFS of 8.1 months were recorded. In previously treated CRC, elisrasib showed significant efficacy as both monotherapy (n=32, ORR 46.9%, mDoR 13.1 months, and mPFS 9.5 months) and in combination with cetuximab (n=29, ORR 62.1%, mDoR 7.0 months, and mPFS 8.2 months). Further studies are planned to evaluate optimized combination strategies to enhance the durability of response in CRC. For late-line PDAC, 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 well-tolerated across NSCLC, CRC, and PDAC populations. Grade 3 or higher treatment-related adverse events (TRAEs) ranged between 8.7% and 15.6% across these indications. Combination therapy with cetuximab was associated with a higher incidence of Grade 3 TRAEs, which were manageable and largely attributed to cetuximab. Only one transient, asymptomatic Grade 4 hypokalemia event was reported, with no other Grade 4 or 5 TRAEs observed.

Expert Commentary

"Elisrasib demonstrates the ability to provide deeper, longer-lasting tumor responses, even in cases where first-generation KRAS G12C inhibitors failed. Overall, these findings indicate that elisrasib may significantly improve treatment for lung cancer patients with KRAS G12C mutations," stated Professor Byoung Chul Cho, MD, PhD, Yonsei Cancer Center, Yonsei University College of Medicine, Korea, and lead study investigator. "Among patients whose disease progressed on first-generation inhibitors, we found five cases of KRAS gene amplification, an important mechanism of evasion of KRAS G12C inhibitor efficacy. Out of those five KRAS amplification cases, four experienced tumor shrinkage, three showed a clinical response, and the disease control rate was 100%, indicating elisrasib's effectiveness in this biomarker-defined group."

Additional D3 Bio Presentations at AACR 2026

D3 Bio also presented advancements in its KRAS program, notably:

• First-in-human phase 1 investigation of D3S-002, a selective ERK1/2 inhibitor, in advanced solid tumors with MAPK pathway mutations — Poster (Abstract CT060)
• Clinical pharmacokinetic modeling of D3S-003, an oral dual-state KRAS G12D inhibitor — Poster (Abstract 1831)
• D3S-003: An allele-specific, orally available KRAS G12D (OFF/ON) inhibitor with best-in-class potential — Poster (Abstract 4569)

"We are encouraged by the consistent and robust clinical activity exhibited by elisrasib across various KRAS G12C–mutant tumors, reinforcing the strength and momentum of D3 Bio's expanding KRAS pipeline," commented Dr. George Chen, Founder, Chairman and Chief Executive Officer of D3 Bio. "These data suggest elisrasib may become a foundational therapy for KRAS G12C mutant cancers."

About Elisrasib (D3S-001)

Elisrasib is a next-generation KRAS G12C inhibitor designed for rapid, complete, and selective target engagement. It covalently binds the GDP-bound (OFF) form of KRAS G12C, effectively blocking nucleotide cycling and suppressing oncogenic signaling. Preclinical studies show robust potency, complete KRAS G12C engagement at clinically relevant exposures, and CNS penetration capability. Elisrasib is currently being evaluated globally in a Phase 2 monotherapy and combination trial across KRAS G12C–mutant solid tumors including NSCLC, CRC, and others.

Key Publications:

Cancer Discovery

Nature Medicine (2025) 31(8):2768–2777

About D3S-002

D3S‑002 is a selective ERK1/2 inhibitor purposely designed for combination approaches, providing vertical MAPK‑pathway inhibition to enhance efficacy and overcome acquired resistance, particularly in tumors previously treated with KRAS G12C inhibitors.

Key Publication:

Cancer Res 1 April 2023; 83 (7_Supplement): 5501.

About D3S-003

D3S‑003 is a differentiated KRAS G12D inhibitor targeting both active (ON) and inactive (OFF) conformations, addressing one of the most common KRAS mutations. This program expands D3 Bio's multi-allele KRAS portfolio, aiming to provide innovative therapies for diverse KRAS-driven malignancies.

About D3 Bio

D3 Bio is a global biotechnology company focused on the discovery, development, and registration of novel oncology and immunology therapies with first or best in class potential. Guided by deep clinical insight and biomarker-driven‑strategies, the Company is advancing a pipeline of programs targeting key oncogenic drivers and immune pathways. D3 Bio owns global rights to all its programs.

For further information, please visit www.d3bio.com

SOURCE D3 Bio