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

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.

Interventions

• AMG 410 · DRUG

  Administered as an oral tablet.

• Pembrolizumab · DRUG

  Administered as an intravenous (IV) infusion.

• Panitumumab · DRUG

  Administered as an IV infusion.

Published eligibility criteria

Verbatim from the registry. Only the site can decide how these apply to a specific patient.

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.

Sites (39)

• City of Hope National Medical Center, Duarte, California · RECRUITING
• University of California Los Angeles, Los Angeles, California · RECRUITING
• Emory University, Atlanta, Georgia · RECRUITING
• Massachusetts General Hospital, Boston, Massachusetts · RECRUITING
• Siteman Cancer Center - Washington University, St Louis, Missouri · RECRUITING
• Duke Cancer Center, Durham, North Carolina · RECRUITING
• Thomas Jefferson University, Philadelphia, Pennsylvania · RECRUITING
• Sarah Cannon Research Institute Oncology Partners, Nashville, Tennessee · RECRUITING
• Next Oncology, San Antonio, Texas · RECRUITING
• Next Virginia, Fairfax, Virginia · RECRUITING
• Chris OBrien Lifehouse, Camperdown, New South Wales, Australia · RECRUITING
• The Queen Elizabeth Hospital, Woodville South, South Australia, Australia · RECRUITING
• Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia · RECRUITING
• Universitair Ziekenhuis Antwerpen, Edegem, Belgium · RECRUITING
• Universitair Ziekenhuis Gent, Ghent, Belgium · RECRUITING
• Cross Cancer Institute, Edmonton, Alberta, Canada · RECRUITING
• Princess Margaret Cancer Centre, Toronto, Ontario, Canada · RECRUITING
• Sir Mortimer B Davis - Jewish General Hospital, Montreal, Quebec, Canada · RECRUITING
• Beijing Cancer Hospital, Beijing, Beijing Municipality, China · RECRUITING
• Chongqing University Cancer Hospital, Chongqing, Chongqing Municipality, China · RECRUITING
• Jinan Central Hospital, Jinan, Shandong, China · RECRUITING
• Rigshospitalet, Copenhagen, Denmark · RECRUITING
• Centre Leon Berard, Lyon, France · RECRUITING
• Gustave Roussy, Villejuif, France · RECRUITING
• Universitaetsklinikum Essen, Essen, Germany · RECRUITING
• Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, Milan, Italy · RECRUITING
• Azienda Ospedaliero Universitaria Pisana, Pisa, Italy · RECRUITING
• Centro Ricerche Cliniche Di Verona Societa responsabilita limitata, Verona, Italy · RECRUITING
• Aichi Cancer Center, Nagoya, Aichi-ken, Japan · RECRUITING
• National Cancer Center Hospital East, Kashiwa-shi, Chiba, Japan · RECRUITING
• National Cancer Center Hospital, Chuo-ku, Tokyo, Japan · RECRUITING
• Universitair Medisch Centrum Utrecht, Utrecht, Netherlands · RECRUITING
• Seoul National University Hospital, Seoul, South Korea · RECRUITING
• Asan Medical Center, Seoul, South Korea · RECRUITING
• Hospital Universitari Vall d Hebron, Barcelona, Catalonia, Spain · RECRUITING
• Fundacion Jimenez Diaz, Madrid, Spain · RECRUITING
• Hospital Universitario 12 de Octubre, Madrid, Spain · RECRUITING
• Sarah Cannon Research Institute UK, London, United Kingdom · RECRUITING
• Royal Marsden Hospital, Sutton, United Kingdom · RECRUITING