The main purpose of the trial is to assess whether the trial drug, KST-6051, is safe and tolerable when administered orally to adults with advanced or metastatic solid tumors with certain KRAS mutations.

This is a first-in-human, phase 1, open-label, multicenter clinical trial designed to evaluate safety, tolerability, pharmacokinetics, biomarkers, pharmacodynamics and preliminary activity of orally administered KST-6051. The trial seeks to enroll adults with advanced or metastatic KRAS mutant solid tumors including but not limited to pancreatic ductal adenocarcinoma, colorectal cancer, and non-small cell lung cancer whose cancers have progressed after prior therapy or in whom standard therapy was not tolerated. The trial includes a dose escalation phase in which higher doses of KST-6051 will be given in subsequent groups of participants. Participants can stay in the trial as long as they benefit from the treatment and can tolerate it.

Inclusion Criteria:

1. Age ≥ 18 years.
2. Willing and able to give written informed consent.
3. Histologically documented locally advanced and unresectable or metastatic NSCLC, PDAC, CRC, or other solid tumor.
4. Documentation of KRAS mutation prior to the first dose of trial drug(s).
5. Progressed on or intolerant to standard treatment(s).
6. Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1.
7. Adequate cardiovascular, hematological, liver, and renal function.
8. Measurable disease at baseline per Response Evaluation Criteria In Solid Tumors version 1.1 (RECIST 1.1).

Exclusion Criteria:

1. Previous or current treatment with RAS or KRAS inhibitors.
2. Central nervous system (CNS) tumors or metastases.
3. Inability to swallow oral medications.
4. Pregnant, breastfeeding, or expecting to conceive or father children within the projected duration of the trial.

Other inclusion/exclusion criteria are specified in the protocol.