Back to Trials
NCT07094113PHASE1Recruiting

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

Amgen

Start Date

7/31/2025

Completion Date

4/20/2031

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.

Detailed Description

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

Age Range: 18 years to No maximum

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.

Interventions

DRUG

AMG 410

DRUG

Pembrolizumab

DRUG

Panitumumab

Interested in This Trial?

Contact the trial locations directly using the information below to learn more about enrollment.

Expressing interest lets you review the study and consent before we connect you with the research site.

Conditions

KRAS Altered Advanced or Metastatic Solid Tumors

Locations

City of Hope National Medical Center

Duarte, California 91010

United States

University of California Los Angeles

Los Angeles, California 90095

United States

Emory University

Atlanta, Georgia 30322

United States

Massachusetts General Hospital

Boston, Massachusetts 02114

United States

Siteman Cancer Center - Washington University

St Louis, Missouri 63110

United States

Duke Cancer Center

Durham, North Carolina 27710

United States

Thomas Jefferson University

Philadelphia, Pennsylvania 19107

United States

Sarah Cannon Research Institute Oncology Partners

Nashville, Tennessee 37203

United States

Next Oncology

San Antonio, Texas 78229

United States

Next Virginia

Fairfax, Virginia 22031

United States

Chris OBrien Lifehouse

Camperdown, New South Wales 2050

Australia

The Queen Elizabeth Hospital

Woodville South, South Australia 5011

Australia

Peter MacCallum Cancer Centre

Melbourne, Victoria 3000

Australia

Universitair Ziekenhuis Antwerpen

Edegem, 2650

Belgium

Universitair Ziekenhuis Gent

Ghent, 9000

Belgium

Cross Cancer Institute

Edmonton, Alberta T6G 1Z2

Canada

Princess Margaret Cancer Centre

Toronto, Ontario M5G 1Z5

Canada

Sir Mortimer B Davis - Jewish General Hospital

Montreal, Quebec H3T 1E2

Canada

Beijing Cancer Hospital

Beijing, Beijing Municipality 100142

China

Chongqing University Cancer Hospital

Chongqing, Chongqing Municipality 400044

China

Jinan Central Hospital

Jinan, Shandong 250013

China

Rigshospitalet

Copenhagen, 2100

Denmark

Centre Leon Berard

Lyon, 69008

France

Gustave Roussy

Villejuif, 94805

France

Universitaetsklinikum Essen

Essen, 45147

Germany

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162

Italy

Azienda Ospedaliero Universitaria Pisana

Pisa, 56126

Italy

Centro Ricerche Cliniche Di Verona Societa responsabilita limitata

Verona, 37134

Italy

Aichi Cancer Center

Nagoya, Aichi-ken 464-8681

Japan

National Cancer Center Hospital East

Kashiwa-shi, Chiba 277-8577

Japan

National Cancer Center Hospital

Chuo-ku, Tokyo 104-0045

Japan

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX

Netherlands

Seoul National University Hospital

Seoul, 03080

South Korea

Asan Medical Center

Seoul, 05505

South Korea

Hospital Universitari Vall d Hebron

Barcelona, Catalonia 08023

Spain

Fundacion Jimenez Diaz

Madrid, 28040

Spain

Hospital Universitario 12 de Octubre

Madrid, 28041

Spain

Sarah Cannon Research Institute UK

London, W1G 6AD

United Kingdom

Royal Marsden Hospital

Sutton, SM2 5PT

United Kingdom