D3 Bio announced that the US Food and Drug Administration (FDA) has cleared two Investigational New Drug (IND) applications: D3S-003 — a KRAS G12D inhibitor — enabling the start of a phase I first-in-human clinical trial and a phase II combination trial evaluating D3S-001 (elisrasib), the company's next-generation KRAS G12C inhibitor, in combination with D3S-002, a selective oral ERK1/2 inhibitor.

D3S-003 is an orally bioavailable, allele-specific KRAS G12D inhibitor that targets both the GDP-bound (OFF) and GTP-bound (ON) conformations. Pre-clinical data demonstrate a differentiated, best-in-class profile with potent anti-tumour activity, favourable drug-like characteristics and a promising safety margin. With FDA clearance received, D3 Bio will advance D3S-003 into a phase I first-in-human study in patients with advanced solid tumours harbouring KRAS G12D mutations.

The newly cleared phase II 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, will investigate safety, pharmacokinetics and early efficacy signals with the goal of establishing a rational combination strategy to address resistance and deliver more durable benefit in KRAS-driven cancers.

"We are excited to receive FDA IND clearance for D3S-003 and to advance a phase II combination clinical trial of elisrasib and D3S-002. With D3S-003, we are bringing a differentiated KRAS G12D inhibitor into the clinic to address one of the most prevalent and challenging KRAS mutations. In parallel, the combination study of elisrasib and D3S-002 pushes forward our next-generation KRAS G12C strategy, particularly for patients who have progressed on prior KRAS G12C-targeted therapies. Together, these milestones underline the momentum of our KRAS franchise and reinforce our commitment to delivering transformative therapies for patients with KRAS-mutant cancers who urgently need new options," said George Chen, Founder, Chairman and Chief Executive Officer, D3 Bio.