This is a study to evaluate the safety and potential anti-tumor activity of an investigational agent called ARV-806 in Adults with Advanced Cancer having a specific KRAS mutation. This is an open-label study which means that participants and study staff will know that all participants will receive ARV-806. Researchers think that ARV-806 can work by breaking down a specific protein with a mutation that is present in some tumors, which might help prevent or slow tumors from growing. This will be the first time ARV-806 will be used in people. The investigational drug will be given through a vein. This is called intravenous (IV) infusion. This study will include 2 parts. In Part A (Phase 1), different small groups of participants will receive lower to higher doses of ARV-806. Adults with advanced cancers having a specific KRAS mutation will be included. In Part B (Phase 2), participants will be assigned to receive one of up to 2 dose levels decided by the information from Part A. Part B will include participants with advanced pancreatic ductal cancer having a specific KRAS mutation.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
159
Intravenous infusion at assigned dose and dosing schedule
Clinical Trial Site
Grand Rapids, Michigan, United States
RECRUITINGClinical Trial Site
Huntersville, North Carolina, United States
RECRUITINGClinical Trial Site
San Antonio, Texas, United States
RECRUITINGClinical Trial Site
Fairfax, Virginia, United States
RECRUITINGPart A (Phase 1): Number of dose-limiting toxicities of ARV-806
Number of participants within a dose escalation cohort with adverse events (AEs) meeting protocol defined dose limiting toxicities during cycle 1 (28 days).
Time frame: 28 days from first ARV-806 administration
Part A (Phase 1): Number of participants with AEs
AEs as characterized by type, frequency, severity (as graded by National Cancer Institute Common Terminology Criteria for Adverse Events \[NCI CTCAE\]), timing, seriousness, and relationship to study intervention as a measure of safety and tolerability
Time frame: From the study baseline to at least 28 days after last dose of ARV-806
Part B (Phase 2): Overall Response Rate (ORR)
ORR is a parameter measuring the anti-tumor activity of ARV-806. ORR is the percentage of participants for whom the study treatment resulted in a complete response or partial response of the disease under study. It is measured using CT/MRI and RECIST 1.1 criteria per investigator assessment.
Time frame: Approximately 2 years
Pharmacokinetics (PK) of ARV-806 (Part A): Area under the plasma or blood concentration-time profile during a dosing interval (AUC0-tau)
Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.
PK of ARV-806 (Part A): Area under the plasma or blood concentration time profile from time zero to the time of the last quantifiable concentration (Clast) (AUC0-last)
Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806
PK of ARV-806 (Part A): Maximum plasma or blood concentration (Cmax)
Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.
PK of ARV-806 (Part A): Minimum observed concentration (Cmin)
Time frame: Timeframe: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.
PK of ARV-806 (Part A): Plasma or blood clearance (CL)
Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.
PK of ARV-806 (Part A): Time for Cmax (Tmax)
Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806.
PK of ARV-806 (Part A): Volume of distribution (Vd)
Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806
Part A: Overall Response Rate (ORR)
Time frame: Approximately 2 years
Part A: Time to Response (TTR)
Time frame: Approximately 2 years
Part A: Duration of Response (DOR)
Time frame: Approximately 2 years
Part A: Disease Control Rate (DCR)
Time frame: Approximately 2 years
Part B: Number of participants with AEs
Time frame: From the study baseline to at least 28 days after last dose of ARV-806
Part B: ARV-806 whole blood pre-dose concentration
Time frame: At predefined intervals throughout the treatment period, up to approximately 6 months after first dose of ARV-806
Part B: Time to Response (TTR)
Time frame: Approximately 2 years
Part B: Duration of Response (DOR)
Time frame: Approximately 2 years
Part B: Disease Control Rate (DCR)
Time frame: Approximately 2 years
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