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AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid Tumors

NCT07094113 · Amgen
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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
About this study
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 criteria
Inclusion Criteria: 1. Age ≥ 18 years (or \> legal age within the country if it is older than 18 years). 2. 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. 3. Participants must have no standard of care treatment options or have actively refused such therapy. 4. Able to swallow and retain per oral administered study treatment. 5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1. 6. Disease measurable as defined by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1), as determined by the site investigator. 7. Adequate organ function. 8. 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). Exclusion Criteria: 1. Untreated symptomatic central nervous system or leptomeningeal metastases. 2. Uncontrolled pleural effusion and/or ascites. 3. History of other malignancy within the past 5 years. 4. 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. 5. History of arterial or venous thrombosis (eg, stroke, transient ischemic attack, pulmonary embolism, or deep vein thrombosis). 6. Live and live-attenuated vaccines are prohibited within 28 days prior to the first dose of study treatment. 7. History of solid organ transplant. 8. Anti-tumor therapy (chemotherapy, antibody therapy, molecular targeted therapy, hormonal therapy, or investigational agent) within 28 days of first dose of study treatment. 9. 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). 10. 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. 11. Therapeutic or palliative radiation therapy within 2 weeks of first dose of study treatment. 12. Major surgery within 28 days of first dose of study treatment. 13. 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.
Study design
Enrollment target: 434 participants
Allocation: non_randomized
Masking: none
Age groups: adult, older_adult
Timeline
Starts: 2025-07-31
Estimated completion: 2031-04-20
Last updated: 2026-02-12
Interventions
Drug: AMG 410Drug: PembrolizumabDrug: Panitumumab
Primary outcomes
  • Number of Participants with Dose Limiting Toxicities (DLTs) (Up to 28 days)
  • Number of Participants with Treatment Emergent Adverse Events (TEAEs) (Up to approximately 3 years)
  • Number of Participants with Serious Adverse Events (SAEs) (Up to approximately 3 years)
Sponsor
Amgen · industry
Contacts & investigators
ContactAmgen Call Center · contact · medinfo@amgen.com · 866-572-6436
InvestigatorMD · study_director, Amgen
All locations (27)
City of Hope National Medical CenterRecruiting
Duarte, California, United States
Emory UniversityRecruiting
Atlanta, Georgia, United States
Massachusetts General HospitalRecruiting
Boston, Massachusetts, United States
Siteman Cancer Center - Washington UniversityRecruiting
St Louis, Missouri, United States
Duke Cancer CenterRecruiting
Durham, North Carolina, United States
Thomas Jefferson UniversityRecruiting
Philadelphia, Pennsylvania, United States
Sarah Cannon Research Institute Oncology PartnersRecruiting
Nashville, Tennessee, United States
Next OncologyRecruiting
San Antonio, Texas, United States
Next VirginiaRecruiting
Fairfax, Virginia, United States
Chris OBrien LifehouseRecruiting
Camperdown, New South Wales, Australia
The Queen Elizabeth HospitalRecruiting
Woodville South, South Australia, Australia
Peter MacCallum Cancer CentreRecruiting
Parkville, Victoria, Australia
Universitair Ziekenhuis GentRecruiting
Ghent, Belgium
Princess Margaret Cancer CentreRecruiting
Toronto, Ontario, Canada
Sir Mortimer B Davis - Jewish General HospitalRecruiting
Montreal, Quebec, Canada
RigshospitaletRecruiting
Copenhagen, Denmark
Centre Leon BerardRecruiting
Lyon, France
Gustave RoussyRecruiting
Villejuif, France
Universitaetsklinikum EssenRecruiting
Essen, Germany
Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano NiguardaRecruiting
Milan, Italy
Centro Ricerche Cliniche Di Verona Societa responsabilita limitataRecruiting
Verona, Italy
Aichi Cancer CenterRecruiting
Nagoya, Aichi-ken, Japan
National Cancer Center Hospital EastRecruiting
Kashiwa-shi, Chiba, Japan
National Cancer Center HospitalRecruiting
Chuo-ku, Tokyo, Japan
Universitair Medisch Centrum UtrechtRecruiting
Utrecht, Netherlands
Fundacion Jimenez DiazRecruiting
Madrid, Spain
Royal Marsden HospitalRecruiting
Sutton, United Kingdom
AMG 410 Alone and in Combination With Other Agents in Participants With KRAS Altered Advanced or Metastatic Solid Tumors · TrialPath