The investigational, selective, covalent, orally bioavailable KRASG12C® inhibitor has a confirmed overall response rate of 57% at the recommended dose of 200 mg twice daily.
Novartis published positive clinical data for JDQ443, an investigational selective, covalent, orally bioavailable KRASG12C inhibitor at the 2022 American Association for Cancer Research (AACR) Annual Meeting, according to a company statement.
Additionally, full information about the discovery of JDQ443 was also included in a poster presented on April 13, 2022, with further details published in the journal, Discovery of cancer.
Preliminary data from the KontRASt-01 study showed that JDQ443 demonstrated anti-tumor activity, high systemic exposure at its recommended dose, and a favorable safety profile for people with kras Solid tumors mutated in G12C.
KontRASt-01 was a multicenter, dose-escalating, open-label, Phase 1b/2 study of the drug in people with advanced solid tumors harboring the kras G12C mutation, including colorectal cancer and NSCLC.
The study began in February 2021 and is recruiting to further characterize the safety profile of the drug as a single agent and in combination with other agents. The estimated primary completion date of the study is 2024.
Investigators found that there was a confirmed overall response rate (ORR) of approximately 57% at the 200 mg dose, twice daily, for people with NSCLC. Additionally, there was a confirmed and unconfirmed ORR of approximately 45% across doses in the NSCLC.
There was a confirmed ORR of approximately 35% for all doses in NSCLC, and pharmacodynamic/pharmacokinetic modeling predicted sustained, high-level target occupancy at the recommended dose of 200 mg twice daily.
Ongoing open-label study enrollment continues in multiple arms for single-agent expansion into kras G12C-mutated NSCLC and colorectal cancer, as well as with TNO155 and tislelizumab against kras Solid tumors mutated in G12C.
A Phase 3, KontRASt-02 study of JDQ443 versus docetaxel for locally advanced, metastatic, or previously treated individuals with kras The G12C-mutated NSCLC is expected to begin recruiting participants by mid-2022.
“After decades without a breakthrough, we as an industry are entering an era of transformation in the targeted treatment of KRAS-mutant cancers,” said Jeff Legos, executive vice president and global head of development, oncology and hematology, Novartis. , in a press release. “Today’s preliminary data is an encouraging signal that we are on the right track as we continue to investigate single-agent and multi-combination strategies designed to improve the efficacy of G12C-targeted therapy and improve patient outcomes with KRAS G12C-induced cancers.”.
Additionally, Novartis also launched its targeted protein degradation platform with a presentation on DKY709, a potential first-in-class “molecular glue” protein degrader designed to target the zing finger transcription factor Helios.
Transcription factors, which are similar to kras G12C, are historically “unrecoverable” targets, according to the release.
The clinical data comes from a study of DKY709 as monotherapy and in combination with the anti-PD-1 antibody spartalizumab as a treatment for advanced solid tumors.
The discovery and structure of DKY709 was also presented at the AACR 2022 Annual Meeting on April 9, 2022.
Novartis announces first clinical data on unique KRASG12C inhibitor at American Association for Cancer Research Annual Meeting. Novartis. Press release. April 11, 2022. Accessed April 12, 2022. https://www.novartis.com/news/media-releases/novartis-announces-early-clinical-data-unique-krasg12c-inhibitor-american-association-cancer-research – annual meeting