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

NCT07094113 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 20240031
• Study Type: interventional
• Target: 434
• Locations: 12 countries
• Sites: 27

Brief 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.

Conditions

KRAS Altered Advanced or Metastatic Solid Tumors

Keywords

Non-small cell lung cancer; NSCLC; Colorectal cancer; CRC; Pancreatic ductal adenocarcinoma; PDAC; AMG 410

Outcome Measures

Primary Outcomes (3)

• 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 Outcomes (13)

• 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

Study Arms (6)

Part 1: Monotherapy Dose Exploration

EXPERIMENTAL

Participants will receive escalating doses of AMG 410.

Drug: AMG 410

Part 1: Food Effect Substudy Cohort

EXPERIMENTAL

A food effect substudy will be conducted. During the substudy, participants will receive AMG 410 under fasted and fed conditions.

Drug: AMG 410

Part 1: China-specific Cohort

EXPERIMENTAL

Participants identified through regionally approved molecular KRAS testing will receive AMG 410.

Drug: AMG 410

Part 2: Monotherapy Dose Expansion

EXPERIMENTAL

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

Part 3a: Combination Therapy Dose Exploration and Dose Expansion

EXPERIMENTAL

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; Drug: Pembrolizumab

Part 3b: Combination Therapy Dose Exploration and Dose Expansion

EXPERIMENTAL

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; Drug: Panitumumab

Interventions

AMG 410 DRUG

Administered as an oral tablet.

Part 1: China-specific Cohort; Part 1: Food Effect Substudy Cohort; Part 1: Monotherapy Dose Exploration; Part 2: Monotherapy Dose Expansion; Part 3a: Combination Therapy Dose Exploration and Dose Expansion; Part 3b: Combination Therapy Dose Exploration and Dose Expansion

Pembrolizumab DRUG

Administered as an intravenous (IV) infusion.

Part 3a: Combination Therapy Dose Exploration and Dose Expansion

Panitumumab DRUG

Administered as an IV infusion.

Part 3b: Combination Therapy Dose Exploration and Dose Expansion

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Amgen: lead

Study Sites (27)

City of Hope National Medical Center

Duarte, California, 91010, United States

RECRUITING

Emory University

Atlanta, Georgia, 30322, United States

RECRUITING

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

RECRUITING

Siteman Cancer Center - Washington University

St Louis, Missouri, 63110, United States

RECRUITING

Duke Cancer Center

Durham, North Carolina, 27710, United States

RECRUITING

Thomas Jefferson University

Philadelphia, Pennsylvania, 19107, United States

RECRUITING

Sarah Cannon Research Institute Oncology Partners

Nashville, Tennessee, 37203, United States

RECRUITING

Next Oncology

San Antonio, Texas, 78229, United States

RECRUITING

Next Virginia

Fairfax, Virginia, 22031, United States

RECRUITING

Chris OBrien Lifehouse

Camperdown, New South Wales, 2050, Australia

RECRUITING

The Queen Elizabeth Hospital

Woodville South, South Australia, 5011, Australia

RECRUITING

Peter MacCallum Cancer Centre

Parkville, Victoria, 3050, Australia

RECRUITING

Universitair Ziekenhuis Gent

Ghent, 9000, Belgium

RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, M5G 1Z5, Canada

RECRUITING

Sir Mortimer B Davis - Jewish General Hospital

Montreal, Quebec, H3T 1E2, Canada

RECRUITING

Rigshospitalet

Copenhagen, 2100, Denmark

RECRUITING

Centre Leon Berard

Lyon, 69008, France

RECRUITING

Gustave Roussy

Villejuif, 94805, France

RECRUITING

Universitaetsklinikum Essen

Essen, 45147, Germany

RECRUITING

Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda

Milan, 20162, Italy

RECRUITING

Centro Ricerche Cliniche Di Verona Societa responsabilita limitata

Verona, 37134, Italy

RECRUITING

Aichi Cancer Center

Nagoya, Aichi-ken, 464-8681, Japan

RECRUITING

National Cancer Center Hospital East

Kashiwa-shi, Chiba, 277-8577, Japan

RECRUITING

National Cancer Center Hospital

Chuo-ku, Tokyo, 104-0045, Japan

RECRUITING

Universitair Medisch Centrum Utrecht

Utrecht, 3584 CX, Netherlands

RECRUITING

Fundacion Jimenez Diaz

Madrid, 28040, Spain

RECRUITING

Royal Marsden Hospital

Sutton, SM2 5PT, United Kingdom

RECRUITING

Related Links

• AmgenTrials clinical trials website

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Colorectal Neoplasms

Interventions

pembrolizumab; Panitumumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases; Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• MD

  Amgen

  STUDY DIRECTOR

Central Study Contacts

Amgen Call Center

CONTACT

866-572-6436; medinfo@amgen.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 23, 2025
• First Posted: July 30, 2025
• Study Start: July 31, 2025
• Primary Completion (Estimated): April 18, 2028
• Study Completion (Estimated): April 20, 2031
• Last Updated: February 12, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR
• 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.
• 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.

Locations

AU (3); NL (1); DK (1); DE (1); CA (2); FR (2); IT (2); GB (1); BE (1); US (9); JP (3); ES (1)