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

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

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.

Study Overview

• Status: Recruiting
• Conditions: KRAS Altered Advanced or Metastatic Solid Tumors
• Intervention / Treatment: Drug: AMG 410; Drug: Pembrolizumab; Drug: Panitumumab

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.

• Study Type: Interventional
• Enrollment (Estimated): 434
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Amgen Call Center; Phone Number: 866-572-6436; Email: medinfo@amgen.com

Study Locations

• Australia
  • New South Wales
    • Camperdown, New South Wales, Australia, 2050
      • Recruiting
      • Chris Obrien Lifehouse
  • South Australia
    • Woodville South, South Australia, Australia, 5011
      • Recruiting
      • The Queen Elizabeth Hospital
  • Victoria
    • Melbourne, Victoria, Australia, 3000
      • Recruiting
      • Peter MacCallum Cancer Centre
• Belgium
  • Ghent, Belgium, 9000
    • Recruiting
    • Universitair Ziekenhuis Gent
• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1Z5
      • Recruiting
      • Princess Margaret Cancer Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • Recruiting
      • Sir Mortimer B Davis - Jewish General Hospital
• China
  • Beijing, China, 100142
    • Recruiting
    • Beijing Cancer hospital
  • Shandong
    • Jinan, Shandong, China, 250013
      • Recruiting
      • Jinan Central Hospital
• Denmark
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Rigshospitalet
• France
  • Lyon, France, 69008
    • Recruiting
    • Centre Leon Berard
  • Villejuif, France, 94805
    • Recruiting
    • Gustave Roussy
• Germany
  • Essen, Germany, 45147
    • Recruiting
    • Universitaetsklinikum Essen
• Italy
  • Milan, Italy, 20162
    • Recruiting
    • Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
  • Pisa, Italy, 56126
    • Recruiting
    • Azienda Ospedaliero Universitaria Pisana
  • Verona, Italy, 37134
    • Recruiting
    • Centro Ricerche Cliniche Di Verona Societa responsabilita limitata
• Japan
  • Aichi-ken
    • Nagoya, Aichi-ken, Japan, 464-8681
      • Recruiting
      • Aichi Cancer Center
  • Chiba
    • Kashiwa-shi, Chiba, Japan, 277-8577
      • Recruiting
      • National Cancer Center Hospital East
  • Tokyo
    • Chuo-ku, Tokyo, Japan, 104-0045
      • Recruiting
      • National Cancer Center Hospital
• Netherlands
  • Utrecht, Netherlands, 3584 CX
    • Recruiting
    • Universitair Medisch Centrum Utrecht
• South Korea
  • Seoul, South Korea, 05505
    • Recruiting
    • Asan Medical Center
  • Seoul, South Korea, 03080
    • Recruiting
    • Seoul National University Hospital
• Spain
  • Madrid, Spain, 28041
    • Recruiting
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28040
    • Recruiting
    • Fundación Jiménez Díaz
• United Kingdom
  • London, United Kingdom, W1G 6AD
    • Recruiting
    • Sarah Cannon Research Institute UK
  • Sutton, United Kingdom, SM2 5PT
    • Recruiting
    • Royal Marsden Hospital
• United States
  • California
    • Duarte, California, United States, 91010
      • Recruiting
      • City of Hope National Medical Center
    • Los Angeles, California, United States, 90095
      • Recruiting
      • University of California Los Angeles
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Recruiting
      • Emory University
  • Massachusetts
    • Boston, Massachusetts, United States, 02114
      • Recruiting
      • Massachusetts General Hospital
  • Missouri
    • St Louis, Missouri, United States, 63110
      • Recruiting
      • Siteman Cancer Center - Washington University
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke Cancer Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19107
      • Recruiting
      • Thomas Jefferson University
  • Tennessee
    • Nashville, Tennessee, United States, 37203
      • Recruiting
      • Sarah Cannon Research Institute Oncology Partners
  • Texas
    • San Antonio, Texas, United States, 78229
      • Recruiting
      • NEXT Oncology
  • Virginia
    • Fairfax, Virginia, United States, 22031
      • Recruiting
      • NEXT Virginia

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Monotherapy Dose Exploration; Participants will receive escalating doses of AMG 410.	Drug: AMG 410; Administered as an oral tablet.
Experimental: Part 1: Food Effect Substudy Cohort; A food effect substudy will be conducted. During the substudy, participants will receive AMG 410 under fasted and fed conditions.	Drug: AMG 410; Administered as an oral tablet.
Experimental: Part 1: China-specific Cohort; Participants identified through regionally approved molecular KRAS testing will receive AMG 410.	Drug: AMG 410; Administered as an oral tablet.
Experimental: Part 2: Monotherapy Dose Expansion; Monotherapy dose expansion of AMG 410 may proceed in KRAS altered tumors in non-small cell lung cancer (NSCLC), colorectal cancer (CRC), pancreatic ductal adenocarcinoma (PDAC), and other KRAS altered tumor types.	Drug: AMG 410; Administered as an oral tablet.
Experimental: Part 3a: Combination Therapy Dose Exploration and Dose Expansion; Part 3a allows for AMG 410 dose exploration and expansion in combination with pembrolizumab in KRAS altered advanced or metastatic solid tumors.	Drug: AMG 410; Administered as an oral tablet.; Drug: Pembrolizumab; Administered as an intravenous (IV) infusion.
Experimental: Part 3b: Combination Therapy Dose Exploration and Dose Expansion; Part 3b allows for AMG 410 dose exploration and expansion in combination with panitumumab in advanced or metastatic CRC and/or PDAC.	Drug: AMG 410; Administered as an oral tablet.; Drug: Panitumumab; Administered as an IV infusion.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants with Dose Limiting Toxicities (DLTs)		Up to 28 days
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.	Up to approximately 3 years
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.	Up to approximately 3 years

Secondary Outcome Measures

Outcome Measure	Time Frame
Overall Survival (OS)	Up to approximately 3 years
Time to Response (TTR) per RECIST v1.1	Up to approximately 3 years
Progression-free Survival (PFS) per RECIST v1.1	Up to approximately 3 years
Maximum Concentration (Cmax) of AMG 410	Up to 85 days
Time to Reach Cmax (Tmax) of AMG 410	Up to 85 days
Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 410	Up to 85 days
Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1	Up to approximately 3 years
Clinical Benefit per RECIST v1.1	Up to approximately 3 years
Duration of Response (DoR) per RECIST v1.1	Up to approximately 3 years
Food Effect Substudy Cohort: Cmax of AMG 410 in the Fed and/or Fasted State	Up to 24 days
Food Effect Substudy Cohort: Tmax of AMG 410 in the Fed and/or Fasted State	Up to 24 days
Food Effect Substudy Cohort: AUC Over the Dosing Interval of AMG 410 in the Fed and/or Fasted State	Up to 24 days
Change From Baseline in Tumor Phosphorylated Extracellular Signal Regulated Kinase (pERK)	Baseline up to approximately 3 years

Collaborators and Investigators

• Sponsor: Amgen
• Investigators: Study Director: MD, Amgen

Publications and helpful links

Helpful Links

• AmgenTrials clinical trials website

Study record dates

Study Major Dates

• Study Start (Actual): July 31, 2025
• Primary Completion (Estimated): April 18, 2028
• Study Completion (Estimated): April 20, 2031

Study Registration Dates

• First Submitted: July 23, 2025
• First Submitted That Met QC Criteria: July 23, 2025
• First Posted (Actual): July 30, 2025

Study Record Updates

• Last Update Posted (Actual): June 12, 2026
• Last Update Submitted That Met QC Criteria: June 11, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: NSCLC; Colorectal cancer; Non-small cell lung cancer; Pancreatic ductal adenocarcinoma; CRC; PDAC; AMG 410
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Intestinal Diseases; Respiratory Tract Diseases; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Lung Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Colonic Diseases; Lung Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Colorectal Neoplasms; Carcinoma, Non-Small-Cell Lung; Amino Acids, Peptides, and Proteins; Proteins; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Serum Globulins; Globulins; Panitumumab; pembrolizumab
• Other Study ID Numbers: 20240031

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request.
• IPD Sharing Time Frame: Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
• IPD Sharing Access Criteria: Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No