KRAS-mutant Colorectal Cancer (CRC), KRAS-mutant Non-small Cell Lung Cancer (NSCLC), KRAS-mutant Pancreatic Ductal Adenocarcinoma (PDAC), Other KRAS-mutant Solid Tumors
Conditions
Keywords
Advanced Solid Tumors, Metastatic Solid Tumors, KRAS Mutation, KST-6051, KRAS, Lung Cancer, Pancreatic Cancer, Colorectal Cancer, Colon Cancer, Rectal Cancer, Endometrial Cancer, Cholangiocarcinoma, Metastatic Cancer, Pan KRAS, Biliary Tract Cancer
Brief summary
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.
Detailed description
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.
Interventions
DRUGKST-6051
KST-6051 will be administered orally as a tablet.
Sponsors
Kestrel Therapeutics, Inc.
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose-limiting Toxicities (DLTs) at the end of Cycle 1 (Each Cycle is 21 Days) | Up to Day 21 of Treatment Cycle 1 | — |
| Number of Participants With Treatment-emergent Adverse Events (TEAEs) | Up to approximately 2 years | Clinically significant changes in safety assessments (vital signs, physical examinations, electrocardiograms, and clinical laboratory tests) are to be reported as adverse events. |
| Number of Participants With Treatment-related Adverse Events (TRAEs) | Up to approximately 2 years | Clinically significant changes in safety assessments (vital signs, physical examinations, electrocardiograms, and clinical laboratory tests) are to be reported as adverse events. |
Secondary
| Measure | Time frame |
|---|---|
| Maximum Observed Blood Concentration (Cmax) of KST-6051 | Up to Week 6 |
| Time to Achieve Cmax (Tmax) of KST-6051 | Up to Week 6 |
| Half-life (t1/2) of KST-6051 | Up to Week 6 |
| Area Under the Blood Concentration-time Curve (AUC) of KST-6051 | Up to Week 6 |
| Objective Response Rate (ORR) | Up to approximately 2 years |
| Disease Control Rate (DCR) | Up to approximately 2 years |
| Duration of Overall Response (DOR) | Up to approximately 2 years |
| Progression-free Survival (PFS) | Up to approximately 2 years |
| Duration of Stable Disease | Up to approximately 2 years |
Countries
United States
Contacts
CONTACTKestrel Therapeutics, Inc.
Outcome results
None listed