The purpose of this first-in-human study is to evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and preliminary efficacy of AMG 410 when administered alone or in combination with other agents in participants with advanced or metastatic solid tumors harboring KRAS alterations. This is a dose-escalation study in which participants will be assigned to multiple dose levels (DLs) of AMG 410, either as monotherapy or in combination with other agents, followed by expansion cohorts. The goal is to determine the Maximum Tolerated Dose (MTD)-the highest dose with acceptable safety and manageable side effects-or the Recommended Phase 2 Dose (RP2D) of AMG 410 in adult participants with KRAS-altered advanced or metastatic solid tumors.
This is a multicenter, multinational, open-label Phase 1/1b study designed to evaluate the safety, tolerability, PK, PD, and preliminary antitumor activity of AMG 410 in adult participants with advanced or metastatic solid tumors characterized by KRAS alterations. The study will begin with a dose-escalation phase, during which AMG 410 will be administered orally, either as monotherapy or in combination with other agents. Dose escalation will follow a model-based approach to identify the MTD or RP2D. Following dose escalation, additional expansion cohorts may be enrolled at selected dose levels to further characterize the safety profile, PK/PD relationships, and preliminary efficacy in specific tumor types or molecular subgroups. Participants will continue treatment until disease progression, unacceptable toxicity, withdrawal of consent, or other protocol-defined discontinuation criteria. The maximum duration of AMG 410 administration in this study is 3 years.
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
434
Administered as an oral tablet.
Administered as an intravenous (IV) infusion.
Administered as an IV infusion.
City of Hope National Medical Center
Duarte, California, United States
RECRUITINGEmory University
Atlanta, Georgia, United States
RECRUITINGMassachusetts General Hospital
Boston, Massachusetts, United States
RECRUITINGSiteman Cancer Center - Washington University
St Louis, Missouri, United States
Number of Participants with Dose Limiting Toxicities (DLTs)
Time frame: Up to 28 days
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Clinically significant changes in safety assessments (vital signs, electrocardiograms \[ECGs\], and clinical laboratory tests) are to be reported as adverse events.
Time frame: Up to approximately 3 years
Number of Participants with Serious Adverse Events (SAEs)
Clinically significant changes in safety assessments (vital signs, ECGs, and clinical laboratory tests) are to be reported as adverse events.
Time frame: Up to approximately 3 years
Maximum Concentration (Cmax) of AMG 410
Time frame: Up to 85 days
Time to Reach Cmax (Tmax) of AMG 410
Time frame: Up to 85 days
Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 410
Time frame: Up to 85 days
Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame: Up to approximately 3 years
Clinical Benefit per RECIST v1.1
Time frame: Up to approximately 3 years
Duration of Response (DoR) per RECIST v1.1
Time frame: Up to approximately 3 years
Time to Response (TTR) per RECIST v1.1
Time frame: Up to approximately 3 years
Progression-free Survival (PFS) per RECIST v1.1
Time frame: Up to approximately 3 years
Overall Survival (OS)
Time frame: Up to approximately 3 years
Food Effect Substudy Cohort: Cmax of AMG 410 in the Fed and/or Fasted State
Time frame: Up to 24 days
Food Effect Substudy Cohort: Tmax of AMG 410 in the Fed and/or Fasted State
Time frame: Up to 24 days
Food Effect Substudy Cohort: AUC Over the Dosing Interval of AMG 410 in the Fed and/or Fasted State
Time frame: Up to 24 days
Change From Baseline in Tumor Phosphorylated Extracellular Signal Regulated Kinase (pERK)
Time frame: Baseline up to approximately 3 years
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Duke Cancer Center
Durham, North Carolina, United States
RECRUITINGThomas Jefferson University
Philadelphia, Pennsylvania, United States
RECRUITINGSarah Cannon Research Institute Oncology Partners
Nashville, Tennessee, United States
RECRUITINGNext Oncology
San Antonio, Texas, United States
RECRUITINGNext Virginia
Fairfax, Virginia, United States
RECRUITINGChris OBrien Lifehouse
Camperdown, New South Wales, Australia
RECRUITING...and 17 more locations