In this single-arm, phase I study (NCT04117087), we evaluated mKRAS-VAX, a pooled mutant KRAS (mKRAS) peptide vaccine targeting six KRAS mutations with nivolumab and ipilimumab in 13 patients with pretreated metastatic MMRp/MSS CRC. mKRAS-VAX elicited an increase in tumor-specific mKRAS-reactive T-cells in 8/12 biomarker-evaluable patients (75%) by direct ex vivo IFNγ ELISpot and in 12 patients (100%) following in vitro expansion. Our findings support further development of mKRAS vaccines with ICIs for advanced MMRp/MSS CRC.

P1, N=448, Recruiting, Alterome Therapeutics, Inc. | N=188 --> 448

Pharmacological inhibition of the MVA pathway with statins effectively blocks KRAS localization to the cell membrane, overcoming KRASi resistance in CRC. Together, these findings identify epigenetic-metabolic coupling of cholesterol biosynthesis as a mechanism of KRASi resistance and highlight targetable metabolic vulnerability in KRAS-mutant CRC.

Using human and murine organoid models, we show that drug-induced inflammatory programs are, at least in part, cancer-cell autonomous, and precede the emergence of drug resistance. We identify TBK1 as a target to abrogate the inflammatory adaptive phase and enhance responses to KRAS inhibition.

P1, N=48, Not yet recruiting, Kumquat Biosciences Inc.

P1, N=101, Recruiting, Suzhou Abogen Biosciences Co., Ltd. | Not yet recruiting --> Recruiting

P1, N=210, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2033 --> Feb 2029 | Trial primary completion date: Jun 2031 --> Feb 2029

P1, N=210, Active, not recruiting, National Cancer Institute (NCI) | Recruiting --> Active, not recruiting

P1/2, N=5, Completed, National Cancer Institute (NCI) | N=70 --> 5 | Recruiting --> Completed

P1, N=101, Not yet recruiting, Suzhou Abogen Biosciences Co., Ltd.

P1, N=237, Active, not recruiting, Quanta Therapeutics | Recruiting --> Active, not recruiting

P1, N=32, Not yet recruiting, Zhejiang Cancer Hospital; Shanghai Ruihongdi Pharmaceutical Co., LTD