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AACR: Verastem, Quanta and Frontier demonstrate KRAS inhibitors KRAS inhibitors' potential in preclinical data

2024-04-11

临床1期AACR会议疫苗临床结果免疫疗法

KRAS mutations are found in lung cancer, pancreatic cancer, ovarian cancer and more.

KRASstem Oncology, Frontier lung cancerQupancreatic cancer aovarian cancer preclinical updates at the American Association for Cancer Research’s (AACR's) annual meeting in San Diego in early April, adding to the ever-growing list of companies vying to bring forth therapies against the once-“undruggable” target.

Verastem Oncologyd Frontier MedicineshaQuanta Therapeutics inhibitor called GFH375/VS-7375, which the company is developing witCancerner GenFleet Therapeutics, is effective against pancreatic and colorectal cancers in mice. The drug works by targeting the KRAS protein in both its “on” and “off” states, meaning when the protein contributes to cell proliferation and when it doesn’t.

VerastemAS G12D inhibitors with preclinical updatKRAS G12D inhibitor KRAS G12D conference included Revolution Medicines’ clinical-stage RMC-9805, which worksGenFleet TherapeuticsAS protein in its “on” pancreatic and colorectal cancerssented data showing that as a monotherapy,KRAS proteinn suppress tumor growth in animal models of pancreatic ductal adenocarcinoma (PDAC) and non-small cell lung cancer (NSCLC). RMC-9805 is currently being studied in a phase 1 clinical trial involving patients with NSCLC, PDAC, colorectal cancer or other solid tumors.

LookinKRAS G12D inhibitors KRAS G12DG12D, Quanta Therapeutics presented a poster with data showing tRevolution MedicinesX3544, which targRMC-9805 G12V, suppressed tumor growth iKRAS proteinls of gastric, pancreatic, lung and ovarian cancers. Frontier Medicines used the AACR event to present a postertumor new data showing that its Kpancreatic ductal adenocarcinoma (PDAC)e siznon-small cell lung cancer (NSCLC)LCRMC-9805orectal cancer, which were derived from the cells of patients who had already beNSCLCeaPDACwicolorectal cancers. Combinisolid tumorsith a PD-1 inhibitor also boosted the efficacy of the PD-1 inhibitor in mouse models of lung cancer, which were less likely to develop central nervous system metastases.

“We really pushed FMCQuanta Therapeuticsto better understand its ability to overcome common resisQTX3544echanisms that hKRAS G12Ved single-acttumorRAS inhibitors and limited their ability to provide meaningful and durableFrontier Medicinese with KRAS G12C cancers,” Frontier's chief medical officer Andrew KrivoKRAS G12C inhibitor KRAS G12C., Ph.D., sFMC-376a press release.tumors NSCLC colorectal cancer KRAS inhibitors KRAS FMC-376 PD-1 PD-1 lung cancer

Like Verastem’s GFFMC-376-7375, Frontier's FMC-376 acts on KRAS in both its “on” and “off” states, but for a different mutation. The two FDA-approKRAS inhibitors KRASKRAS G12C inhibitors, Amgen’s Lumakras and Mirati Therapeutics' Krazati, act on the molecule onlKRAS G12C cancersate. So far, FMC-376 has the potential to be a first-in-class drug.

In otVerastemy-stage KRAS news from the conFMC-376, scientiKRASfrom Johns Hopkins University presented data from a phase 1 trial showing that an off-tKRAS G12Ccancer vaccinAmgeninsLumakrasx mosMirati TherapeuticsioKrazatiDAC generated T cells specific to the mutations in patiFMC-376th PDAC who also received a combination of Bristol Myers Squibb's immunotherapies Opdivo and Yervoy.

Editor's note: A prevKRAS version of this story also referred to RevJohns Hopkins UniversityRMC-6236 in combination with RMC-9805. The presentation on RMC-6236cancern combination with a different drug aKRAShis reference PDACnow been removed from the article.PDAC Bristol Myers Squibb Opdivo Yervoy

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