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

NCT ID: NCT07094113

Last Updated: 2025-11-06

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE1

Total Enrollment

434 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-31

Study Completion Date

2030-09-09

Brief Summary

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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

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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.

Conditions

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KRAS Altered Advanced or Metastatic Solid Tumors

Keywords

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

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SEQUENTIAL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Part 1: Monotherapy Dose Exploration

Participants will receive escalating doses of AMG 410.

Group Type EXPERIMENTAL

AMG 410

Intervention Type DRUG

Administered as an oral tablet.

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.

Group Type EXPERIMENTAL

AMG 410

Intervention Type DRUG

Administered as an oral tablet.

Part 1: China-specific Cohort

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

Group Type EXPERIMENTAL

AMG 410

Intervention Type DRUG

Administered as an oral tablet.

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.

Group Type EXPERIMENTAL

AMG 410

Intervention Type DRUG

Administered as an oral tablet.

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.

Group Type EXPERIMENTAL

AMG 410

Intervention Type DRUG

Administered as an oral tablet.

Pembrolizumab

Intervention Type DRUG

Administered as an intravenous (IV) infusion.

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.

Group Type EXPERIMENTAL

AMG 410

Intervention Type DRUG

Administered as an oral tablet.

Panitumumab

Intervention Type DRUG

Administered as an IV infusion.

Interventions

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AMG 410

Administered as an oral tablet.

Intervention Type DRUG

Pembrolizumab

Administered as an intravenous (IV) infusion.

Intervention Type DRUG

Panitumumab

Administered as an IV infusion.

Intervention Type DRUG

Eligibility Criteria

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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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Amgen

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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MD

Role: STUDY_DIRECTOR

Amgen

Locations

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City of Hope National Medical Center

Duarte, California, United States

Site Status RECRUITING

Next Oncology

San Antonio, Texas, United States

Site Status RECRUITING

Next Virginia

Fairfax, Virginia, United States

Site Status RECRUITING

The Queen Elizabeth Hospital

Woodville South, South Australia, Australia

Site Status RECRUITING

Peter MacCallum Cancer Centre

Parkville, Victoria, Australia

Site Status RECRUITING

Princess Margaret Cancer Centre

Toronto, Ontario, Canada

Site Status RECRUITING

Countries

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United States Australia Canada

Central Contacts

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Amgen Call Center

Role: CONTACT

Phone: 866-572-6436

Email: [email protected]

Related Links

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http://www.amgentrials.com

AmgenTrials clinical trials website

Other Identifiers

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20240031

Identifier Type: -

Identifier Source: org_study_id