AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid Tumors
Trial statusRecruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAmgen
About this trial
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.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Age ≥ 18 years (or > legal age within the country if it is older than 18 years).
Pathologically documented, locally-advanced or metastatic malignancy with any missense mutation in the KRAS gene or evidence of KRAS amplification using an analytically validated KRASWT amplification assay.
Participants must have no standard of care treatment options or have actively refused such therapy.
Able to swallow and retain per oral administered study treatment.
Disqualifiers
Untreated symptomatic central nervous system or leptomeningeal metastases.
Uncontrolled pleural effusion and/or ascites.
History of other malignancy within the past 5 years.
Active systemic infection or symptoms that indicate an acute and/or uncontrolled infection requiring IV antibiotics within 7days prior to the first dose of study treatment.
Trial design
Design model
Sequential
Treatments tested in this trial
AMG 410
DrugAdministered as an oral tablet.
Pembrolizumab
DrugAdministered as an intravenous (IV) infusion.
Panitumumab
DrugAdministered as an IV infusion.
Treatment groups
434 Participants
are divided into 6 treatment groups6
Treatment groupsSee each treatment group below.
Group A: Part 1: Monotherapy Dose ExplorationExperimental treatment 1 intervention
Group B: Part 1: Food Effect Substudy CohortExperimental treatment 1 intervention
Group C: Part 1: China-specific CohortExperimental treatment 1 intervention
Group D: Part 2: Monotherapy Dose ExpansionExperimental treatment 1 intervention
Group E: Part 3a: Combination Therapy Dose Exploration and Dose ExpansionExperimental treatment 2 interventions
Group F: Part 3b: Combination Therapy Dose Exploration and Dose ExpansionExperimental treatment 2 interventions
Trial outcomes
Primary outcomes
1
Number of Participants with Dose Limiting Toxicities (DLTs)
Time frame
Up to 28 days2
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 years3
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 yearsSecondary outcomes
1
Maximum Concentration (Cmax) of AMG 410
Time frame
Up to 85 days2
Time to Reach Cmax (Tmax) of AMG 410
Time frame
Up to 85 days3
Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 410
Time frame
Up to 85 days4
Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Time frame
Up to approximately 3 years Source ClinicalTrials.gov