AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid Tumors
Solid Tumor
Unknown Primary
18 Years and older, Male and Female
20240031 (primary)
NCI-2025-07560
Summary
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.
Objectives
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.
Eligibility
- 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.
- Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1.
- Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), as determined by the site investigator.
- Adequate organ function.
- Archival (formalin-fixed, paraffin-embedded [FFPE]) tumor tissue or block collected within 5 years before screening must be available. Participants without archived tumor tissue may undergo tumor biopsy before AMG 410 dosing (Day1).
Treatment Sites in Georgia
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