On June 1, 2026 Ranok Therapeutics, a clinical-stage biotechnology company developing innovative therapies, reported positive interim Phase 1 clinical data for RNK08954, an investigational oral, selective KRAS G12D inhibitor. The results were featured in an Oral Presentation at the 2026 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting. The multicenter Phase 1 study (NCT06667544) evaluated RNK08954 in heavily pre-treated patients with KRAS G12D-mutated solid tumors in China.
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Based on comprehensive assessment of safety, tolerability, pharmacokinetics, and anti-tumor activity, a dose of 1200 mg once daily (QD) was selected as the Recommended Phase 2 Dose (RP2D).
In the cohort of patients (N=47) with metastatic non-small cell lung cancer (NSCLC), RNK08954 demonstrated enhanced anti-tumor activity. In the overall evaluable NSCLC population across all tested doses (400–1200 mg, QD), the Objective Response Rate (ORR) was 42.6% (95% confidence interval (CI), 28.3%–57.8%), alongside a Disease Control Rate (DCR) of 95.7% (95% CI, 85.5%–99.5%).
Clinical activity was further enhanced at the RP2D of 1200 mg QD. Patients with only one prior line of therapy achieved an ORR of 45.0% (95% CI, 23.1%–68.5%), and DCR of 95.0% (95% CI, 75.1%–99.9%). Notably, patients who were taxane-naïve achieved the highest response rate in the study, with ORR of 50.0% (95% CI, 26.0%–74.0%) and DCR of 94.4% (95% CI, 72.7%–99.9%), demonstrating the potent antitumor activity of RNK08954. Longitudinal follow-up demonstrated durable clinical benefit. Progression-free survival (PFS) data for the optimized 1200 mg QD cohort remain immature and continue to mature. In the pooled lower-dose cohorts (400–1000 mg QD), RNK08954 achieved a median PFS of 7.6 months (95% CI, 2.8–NR). Robust molecular responses were evidenced by circulating tumor DNA (ctDNA) kinetics, corroborating the radiologic responses. Among the evaluable patients, 83.3% achieved a critical biological threshold of ≥50% variant allele frequency (VAF) clearance of the mutant KRAS G12D clone. Crucially, 44.4% of patients achieved complete molecular clearance of the driver mutation, providing strong biological validation of RNK08954 potent target engagement and mechanism of action.
Professor Zhengbo Song, MD, PhD, Lead Investigator, Zhejiang Cancer Hospital commented "These interim data are highly encouraging for patients with advanced KRAS G12D-mutated NSCLC who currently face limited treatment options. Achieving a 50.0% response rate specifically in taxane-naïve patients at the 1200 mg RP2D provides a strong scientific rationale for moving RNK08954 into earlier lines of therapy, before the introduction of traditional chemotherapy. Combined with a favorable, manageable safety profile, RNK08954 demonstrates the potential to significantly shift how we sequence treatments for these patients."
"The clinical activity and tolerability observed at the 1200 mg QD dose level confirm that RNK08954 is a highly competitive agent in the KRAS G12D landscape. The robust responses in taxane-naïve patients strongly support our strategy to explore RNK08954 in earlier treatment lines." said Iman El-Hariry, MD, PhD, Chief Medical Officer, Ranok Therapeutics. "Our immediate focus is on swift clinical execution to fully characterize this monotherapy profile in broader NSCLC populations while systematically exploring RNK08954’s potential in rational combination regimens."
"The clinical results demonstrated by RNK08954 at ASCO (Free ASCO Whitepaper) represent a significant corporate milestone for Ranok Therapeutics, establishing a well-tolerated, active oral profile at the RP2D." commented Weiwen Ying, PhD, Chief Executive Officer, Ranok Therapeutics. "This strong data package provides us with excellent strategic flexibility as we evaluate corporate development opportunities to accelerate our clinical programs. These results also offer a powerful validation of our internal discovery platform, giving us high confidence as we advance our broader multi-asset KRAS franchise spanning G12D, G12C, and beyond."
About RNK08954
RNK08954 is a highly selective, oral KRAS G12D inhibitor with unique pharmacokinetic properties designed for deep, sustained target inhibition. It is currently being investigated as monotherapy and in combination with chemotherapy and/or other targeted agents in NSCLC, PDAC, and additional solid tumor indications.
(Press release, Ranok Therapeutics, JUN 1, 2026, View Source [SID1234666326])