AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid Tumors
- 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.
- Short title
- AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid Tumors
- Official title
- A Phase 1/1b Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid Tumors
- Control arm
- Open label
- Registry reports results
- Listing at source
- Listed
- Recruitment status
- Recruiting
- Phase
- Phase 1
- Study type
- Interventional
- Completion date
- 2031-04-20
- First posted
- 2025-07-30
- Registry last updated
- 2026-07-30
- Primary completion date
- 2028-04-18
- Start date
- 2025-07-31
- Participants
- Participant count basis
- Estimated
- Planned participants
- Protocol amendments
- Number of sites
- Data monitoring committee
- Registry sponsor category
- Industry
- Lead sponsor
- Amgen
- Source registry
- ClinicalTrials.gov
- Registry ID
- NCT07094113
- ClinicalTrials.gov ID
- NCT07094113
- Registry record
- Open registry record
- Allocation
- Not randomised
- Model
- Sequential
- Purpose
- Treatment
- Masking
- No masking
Number of Participants with Dose Limiting Toxicities (DLTs)
Timeframe: Up to 28 days
Number of Participants with Treatment Emergent Adverse Events (TEAEs)
Timeframe: Up to approximately 3 years
Clinically significant changes in safety assessments (vital signs, electrocardiograms \[ECGs\], and clinical laboratory tests) are to be reported as adverse events.
Number of Participants with Serious Adverse Events (SAEs)
Timeframe: Up to approximately 3 years
Clinically significant changes in safety assessments (vital signs, ECGs, and clinical laboratory tests) are to be reported as adverse events.
Maximum Concentration (Cmax) of AMG 410
Timeframe: Up to 85 days
Time to Reach Cmax (Tmax) of AMG 410
Timeframe: Up to 85 days
Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 410
Timeframe: Up to 85 days
Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1
Timeframe: Up to approximately 3 years
Clinical Benefit per RECIST v1.1
Timeframe: Up to approximately 3 years
Duration of Response (DoR) per RECIST v1.1
Timeframe: Up to approximately 3 years
Time to Response (TTR) per RECIST v1.1
Timeframe: Up to approximately 3 years
Progression-free Survival (PFS) per RECIST v1.1
Timeframe: Up to approximately 3 years
Overall Survival (OS)
Timeframe: Up to approximately 3 years
Food Effect Substudy Cohort: Cmax of AMG 410 in the Fed and/or Fasted State
Timeframe: Up to 24 days
Food Effect Substudy Cohort: Tmax of AMG 410 in the Fed and/or Fasted State
Timeframe: Up to 24 days
Food Effect Substudy Cohort: AUC Over the Dosing Interval of AMG 410 in the Fed and/or Fasted State
Timeframe: Up to 24 days
Change From Baseline in Tumor Phosphorylated Extracellular Signal Regulated Kinase (pERK)
Timeframe: Baseline up to approximately 3 years
- Sex
- All
- Age groups
- Adults, Older adults
- Minimum age
- 18 Years
- Healthy volunteers
- No
- 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).
- 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.
- History of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis).
- Live and live-attenuated vaccines are prohibited within 28 days prior to the first dose of study treatment.
- History of solid organ transplant.
- Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, hormonal therapy, or investigational agent) within 28 days of first dose of study treatment.
- Presence or history of any of the following viral infections: HIV, Hepatitis C, Hepatitis B, and active severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
- Toxicities from prior anti-tumor therapy (including radiotherapy) not having improved to at least Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 grade 1.
- Therapeutic or palliative radiation therapy within 2 weeks of first dose of study treatment.
- Major surgery within 28 days of first dose of study treatment.
- History or evidence of any other clinically significant disorder, condition, or disease that, in the opinion of the investigator, would pose a risk to participant safety.
- City of Hope National Medical CenterDuarte, United StatesRecruiting
- University of California Los AngelesLos Angeles, United StatesRecruiting
- Emory UniversityAtlanta, United StatesRecruiting
- Massachusetts General HospitalBoston, United StatesRecruiting
- Siteman Cancer Center - Washington UniversitySt Louis, United StatesRecruiting
- Duke Cancer CenterDurham, United StatesRecruiting
- Thomas Jefferson UniversityPhiladelphia, United StatesRecruiting
- Sarah Cannon Research Institute Oncology PartnersNashville, United StatesRecruiting
- Next OncologySan Antonio, United StatesRecruiting
- Next VirginiaFairfax, United StatesRecruiting
- Chris OBrien LifehouseCamperdown, AustraliaRecruiting
- The Queen Elizabeth HospitalWoodville South, AustraliaRecruiting
- Peter MacCallum Cancer CentreMelbourne, AustraliaRecruiting
- Universitair Ziekenhuis AntwerpenEdegem, BelgiumRecruiting
- Universitair Ziekenhuis GentGhent, BelgiumRecruiting
- Cross Cancer InstituteEdmonton, CanadaRecruiting
- Princess Margaret Cancer CentreToronto, CanadaRecruiting
- Sir Mortimer B Davis - Jewish General HospitalMontreal, CanadaRecruiting
- Beijing Cancer HospitalBeijing, ChinaRecruiting
- Chongqing University Cancer HospitalChongqing, ChinaRecruiting
- Jinan Central HospitalJinan, ChinaRecruiting
- RigshospitaletCopenhagen, DenmarkRecruiting
- Centre Leon BerardLyon, FranceRecruiting
- Gustave RoussyVillejuif, FranceRecruiting
- Universitaetsklinikum EssenEssen, GermanyRecruiting
And 14 more, listed on the interactive page.
- Related resource (www.amgentrials.com)