KST-6051 Receives FDA Fast Track Designation in KRAS-Mutant Solid Tumors

The FDA has granted fast track designation to KST-6051, an oral pan-KRAS inhibitor, for the treatment of patients with advanced or metastatic solid tumors harboring KRAS mutations, according to a news release from the developer, Kestrel Therapeutics.¹ Notably, the clinical development of KST-6051 is targeted towards pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and non–small cell lung cancer (NSCLC), among other KRAS-driven cancers.

The designation is based on the strength of KST-6051’s preclinical data package, according to the drug’s developer. KST-6051 is currently being evaluated in the first-in-human, dose-escalation phase 1 FALCON trial (NCT07458347), which is enrolling patients with KRAS-mutant advanced or metastatic solid tumors.

“FDA fast track designation for KST-6051 is an important regulatory milestone for Kestrel, based on the strength of our preclinical data package. This designation will allow us to work more closely with the FDA as we advance KST-6051 through our ongoing phase 1 study, with the goal of bringing a much-needed treatment option to patients with KRAS-mutant tumors as efficiently as possible,” stated Frank Haluska, MD, PhD, president and chief executive officer of Kestrel Therapeutics, in the press release.¹

What is the design of the FALCON trial?

FALCON is evaluating the safety, tolerability, pharmacokinetics, and preliminary antitumor activity of KST-6051 in patients with advanced or metastatic solid tumors harboring KRAS mutations, including PDAC, CRC, NSCLC, and other KRAS-driven malignancies.² The company announced that the first patient was dosed on April 28, 2026.³

The trial has enrolled patients who are 18 years or older with histologically documented locally advanced or unresectable disease with documentation of a KRAS mutation prior to the first treatment dose and progression on or intolerance to standard treatments. Patients also had an ECOG performance status of 0 or 1, adequate cardiovascular, hematological, liver, and renal function, and measurable disease per RECIST v1.1.

Exclusion criteria included previous or current treatment with RAS or KRAS inhibitors, central nervous system tumors or metastases, and inability to swallow oral medications. The trial’s dose-escalation phase will be followed by expansion cohorts in selected tumor types.

The primary end points of the study are the number of patients with dose-limiting toxicities, treatment-emergent adverse events, or treatment-related adverse events. Secondary end points include half-life of KST-6051, objective response rate, disease control rate, progression-free survival, and duration of stable disease.

In the trial, patients will be assigned to sequential cohorts with increasing doses of KST-6051, which is to be administered as an oral tablet, to determine the recommended dose for expansion. Treatment continues as long as patients benefit from treatment and can tolerate it.

How does KST-6051 work?

KST-6051 is designed as a potent and selective inhibitor of KRAS with activity against the protein in both its active, GTP-bound state and its inactive, GDP-bound state. In preclinical models, the agent demonstrated on-target pathway modulation, anti-proliferative activity, and efficacy at well-tolerated doses across multiple human KRAS-mutant tumor models.¹ Kestrel’s clinical development plans for KST-6051 are ultimately intended to address PDAC, CRC, NSCLC, and other KRAS-driven malignancies.

How does KST-6051 fit into the KRAS-mutant solid tumor treatment landscape?

KST-6051 joins a growing field of agents targeting mutant KRAS across solid tumor types. Previously, the FDA granted breakthrough therapy designation to olomorasib for previously treated, KRAS G12C-mutant advanced pancreatic cancer.⁴ Additionally, preliminary data from the phase 1/2 TARGET-D 101 trial (NCT07020221) demonstrated that VS-7375 elicited clinical activity across KRAS G12D-mutated pancreatic, colorectal, and lung cancers.⁵

Kestrel, the developer of KST-6051, has also entered a strategic agreement granting AbbVie an exclusive option to acquire the company based on defined development and regulatory milestones, according to the release.¹

References

1. Kestrel Therapeutics receives FDA fast track designation for KST-6051, a potential best-in-class pan-KRAS inhibitor, in the treatment of KRAS-mutant advanced solid tumors. News release. Kestrel Therapeutics, Inc. September 15, 2026. Accessed September 16, 2026. https://tinyurl.com/muuad87b
2. A phase 1 dose-escalation trial of KST-6051 in patients with advanced solid tumors with kirsten rat sarcoma viral oncogene homolog (KRAS) mutation. ClinicalTrials.gov. Updated June 29, 2026. Accessed September 16, 2026. https://tinyurl.com/mvjpzhza
3. Kestrel Therapeutics announces first patient dosed in the phase 1 clinical trial of KST-6051, a potential best-in-class pan-KRAS inhibitor, in patients with KRAS-driven malignancies. News release. Kestrel Therapeutics, Inc. April 28, 2026. Accessed September 16, 2026. https://tinyurl.com/8bcux7ym
4. Lilly's olomorasib receives U.S. FDA's breakthrough therapy designation for the treatment of previously treated KRAS G12C-mutant advanced pancreatic cancer. News release. Eli Lilly and Company. August 3, 2026. Accessed September 16, 2026. https://tinyurl.com/58t92era
5. Verastem Oncology announces positive preliminary data from the TARGET-D 101 phase 1/2 trial of VS-7375 in advanced KRAS G12D-mutated solid tumors. News release. Verastem Oncology. June 24, 2026. Accessed September 16, 2026. https://tinyurl.com/yszwe53u