Ranok Therapeutics' KRAS G12D inhibitor shows 58% response rate in non-small cell lung cancer

Phase Ia data for RNK08954, an oral KRAS G12D inhibitor developed by Ranok Therapeutics, show an overall objective response rate of 28% and a disease control rate of 86% across 36 evaluable patients with advanced solid tumors, with a notably higher response rate in the non-small cell lung cancer subgroup, according to results [published in Cancer Discovery](https://www.prnewswire.com/news-releases/ranok-therapeutics-announces-the-publication-of-positive-phase-1a-clinical-results-for-kras-g12d-inhibitor-rnk08954-in-cancer-discovery-302767728.html). The findings mark one of the earlier clinical readouts for a selective KRAS G12D-directed small molecule in this mutation class. Ranok operates out of Hangzhou, China, and Boston, Massachusetts. In the NSCLC cohort, RNK08954 produced an ORR of 58.33% and a DCR of 100%, the company said. Across the full 36-patient evaluable population, the safety profile was characterized predominantly by Grade 1–2 gastrointestinal adverse events and decreased appetite. No dose-limiting toxicities were observed during dose escalation, and the study identified a recommended dose for expansion. The trial was conducted across multiple sites in China. The [Phase Ia study ](https://app.allsci.com/clinical-trial/ASC-CT-0000000055053-1.0-1745763661)enrolled patients with advanced solid tumors harboring the KRAS G12D mutation, with the primary objectives of assessing safety, tolerability, and clinical activity, and determining the recommended dose for expansion. The evaluable population of 36 patients represents a subset of those enrolled; full enrollment figures were not disclosed in the company announcement. The data are preliminary, and the study was not designed as a randomized or controlled comparison. Cross-cohort interpretation is constrained by the single-arm design and the relatively small patient numbers within individual tumor-type subgroups. RNK08954 binds directly to the Switch II pocket of KRAS G12D in both its active and inactive conformational states, a mechanism shared with other covalent and non-covalent KRAS-directed inhibitors in development. The KRAS G12D mutation is among the most prevalent oncogenic alterations in solid tumors, present in a substantial proportion of pancreatic ductal adenocarcinoma, colorectal cancer, and NSCLC cases. Sotorasib (Lumakras) and adagrasib (Krazati), both approved by US FDA, target the distinct KRAS G12C variant and are not active against G12D; no KRAS G12D inhibitor has yet received regulatory approval. Ranok said it has initiated a Phase Ib expansion study evaluating RNK08954 as monotherapy and in [combination regimens ](https://app.allsci.com/clinical-trial/ASC-CT-0000001121009-1.0-1770124530)across NSCLC, [pancreatic cancer](https://app.allsci.com/clinical-trial/ASC-CT-0000001084761-1.0-1766586267), and other indications. Cross-trial comparisons are limited by differences in study design, duration, and patient populations. *** This article was generated with AI assistance and reviewed and edited by the AllSci editorial team Explore more at AllSci News: [https://allsci.com/news/](https://allsci.com/news/) --- Spot something wrong? [Report an issue with this article](https://newsgen-prod.reframedata.com/feedback/rnk08954-lung-cancer-ranok-therapeutics-shows-58)