KRAS Altered Advanced or Metastatic Solid Tumors
Conditions
Interventions
Experimental: Part 1: Monotherapy Dose Exploration
- Participants will receive escalating doses of AMG 410.
- Interventions: Drug: AMG 410
Experimental: Part 2: Monotherapy Dose Expansion
- Monoth
Sponsors
Nakatani Iwami
Eligibility
Sex/Gender
All
Inclusion criteria
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
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.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 1. Number of Participants with Dose Limiting Toxicities (DLTs) [Time Frame: Up to 28 days] 2. Number of Participants with Treatment Emergent Adverse Events (TEAEs) [Time Frame: Up to approximately 3 years] Clinically significant changes in safety assessments (vital signs, electrocardiograms [ECGs], and clinical laboratory tests) are to be reported as adverse events. 3. Number of Participants with Serious Adverse Events (SAEs) [Time Frame: Up to approximately 3 years] Clinically significant changes in safety assessments (vital signs, ECGs, and clinical laboratory tests) are to be reported as adverse events. | — |
Secondary
| Measure | Time frame |
|---|---|
| 1. Maximum Concentration (Cmax) of AMG 410 [Time Frame: Up to 85 days] 2. Time to Reach Cmax (Tmax) of AMG 410 [Time Frame: Up to 85 days] 3. Area Under the Concentration-time Curve (AUC) Over the Dosing Interval of AMG 410 [Time Frame: Up to 85 days] 4. Confirmed Objective Response (OR) per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 [Time Frame: Up to approximately 3 years] 5. Clinical Benefit per RECIST v1.1 [Time Frame: Up to approximately 3 years] 6. Duration of Response (DoR) per RECIST v1.1 [Time Frame: Up to approximately 3 years] 7. Time to Response (TTR) per RECIST v1.1 [Time Frame: Up to approximately 3 years] 8. Progression-free Survival (PFS) per RECIST v1.1 [Time Frame: Up to approximately 3 years] 9. Overall Survival (OS) [Time Frame: Up to approximately 3 years] 10. Change From Baseline in Tumor Phosphorylated Extracellular Signal Regulated Kinase (pERK) [Time Frame: Baseline up to approximately 3 years] | — |
Countries
Australia, Japan, United States
Contacts
Public ContactContact Local
Amgen K.K.
Outcome results
None listed