RAS wild-type

P2, N=34, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jan 2026 --> Feb 2027

P2, N=37, Recruiting, Memorial Sloan Kettering Cancer Center | Trial primary completion date: Jun 2026 --> Jul 2027

As a first-line treatment for patients with left-sided all RAS or KRAS wild-type mCRC, panitumumab plus doublet chemotherapy may be suggested better efficacy outcomes than cetuximab plus doublet chemotherapy.

P1/2, N=151, Not yet recruiting, Takeda

P1, N=30, Recruiting, Lyell Immunopharma, Inc. | Trial completion date: Oct 2024 --> Jun 2032 | Trial primary completion date: Oct 2023 --> Jun 2028

Our findings demonstrate that the endogenously expressed oncogenic KRAS mutations exacerbate the replication stress and reveal KRAS allele-specific replication phenotypes, facilitating the development of effective chemotherapies tailored to specific oncogenic KRAS mutation alleles and types of cancer. Moreover, our study offers valuable model cell lines for investigating mechanisms underlying replication vulnerability in cancers harbouring oncogenic KRAS mutations.

In silico analysis further suggests that the mutations confer increased GEF-binding ability versus wild-type. Results of the study highlight the need to characterize Ras isoform- and mutation-specific phenotypic effects, which may have repercussions in CRC management.

In this phase 1 study involving heavily pretreated patients, the most common adverse events associated with rezatapopt were nausea and vomiting. Antitumor activity occurred across multiple tumor types, providing proof of concept for p53 reactivation. (Funded by PMV Pharmaceuticals; PYNNACLE ClinicalTrials.gov number, NCT04585750.).

RAS mutations are independent predictors of poor local control and survival after IGTA in CRLM. Evaluate interactions between RAS genotype and commonly used targeted agents in the peri-ablative setting. These integrated, real-world insights support the development of genotype-guided ablation planning and peri-ablative systemic therapy strategies.

P3, N=94, Recruiting, SWOG Cancer Research Network | Not yet recruiting --> Recruiting

P3, N=408, Not yet recruiting, University Hospital, Rouen | Trial completion date: Jan 2031 --> Jun 2032 | Trial primary completion date: Jan 2031 --> Jun 2032

Subsequently, the drug library screened out disulfiram, which primarily exerts a synthetic lethal effect by inhibiting IL-1β in KRAS-mutant BTC...These synthetically lethal effects were confirmed using PDX, a KRAS oncogene-driven tumor model, as well as in other KRAS-mutant cancer cell lines. In summary, these results indicate that inhibiting GATA2/IL1β could be a therapeutic strategy in KRAS-mutant BTC and potentially other cancers.