AMG 510 Ethnic Sensitivity Study (CodeBreaK 105).

A Phase 1, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, and Efficacy of AMG 510 in Subjects of Chinese Descent With Advanced/Metastatic Solid Tumors With KRAS p.G12C Mutation (CodeBreaK 105)

To evaluate safety, tolerability, PK, and preliminary efficacy of AMG 510 PO QD in subjects of Chinese descent with KRAS p.G12C-mutant advanced/metastatic solid tumors.

Study Overview

• Status: Active, not recruiting
• Conditions: Advanced/Metastatic Solid Tumors With KRAS p.G12C Mutation
• Intervention / Treatment: Drug: AMG 510

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Phase 1

Contacts and Locations

Study Locations

• Hong Kong
  • Hong Kong, Hong Kong
    • University of Hong Kong, Queen Mary Hospital
  • Shatin, New Territories, Hong Kong
    • Prince of Wales Hospital
• Taiwan
  • Taichung, Taiwan, 40705
    • Veterans General Hospital - Taichung
  • Taipei, Taiwan, 10002
    • National Taiwan University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

• Male or female subjects greater than or equal to 18 years old
• Subject is of Chinese ancestry
• Pathologically documented, advanced/metastatic solid tumor with KRAS p.G12C mutation identified

Exclusion Criteria:

• Active brain metastases from non-brain tumors.
• Myocardial infarction within 6 months of study day 1.
• Gastrointestinal (GI) tract disease causing the inability to take oral medication

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Arm; Subjects will be enrolled and will receive AMG 510 PO QD.	Drug: AMG 510; Subjects will be enrolled and will receive AMG 510 PO QD.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Dose-limiting Toxicities (DLT)	DLTs were defined as any of the following adverse events (AEs) where a relationship to sotorasib could not be ruled out. Hematological toxicity; febrile neutropenia; neutropenic infection; grade 4 neutropenia; grade ≥ 3 thrombocytopenia for > 7 days; grade 3 thrombocytopenia with grade ≥ 2 bleeding; grade 4 thrombocytopenia; grade 4 anemia. Non-hematological toxicity; grade ≥ 4 vomiting or diarrhea; grade 3 diarrhea or grade 3 vomiting lasting more than 3 days despite optimal medical support; grade ≥ 3 nausea for 3 days or more despite optimal medical support; any other grade ≥ 3 adverse event.	Day 1 to Day 21
Number of Participants With Treatment-emergent AEs (TEAEs)	An AE was any untoward medical occurrence in a clinical study participant irrespective of a causal relationship with the study treatment. A TEAE was defined as an AE starting on or after first dose of study treatment. Treatment-related TEAEs were any TEAEs considered related to investigational product by the investigator. If relationship was missing, the event was assumed treatment-related. Clinically significant changes from the participant's baseline values in vital signs, 12-lead electrocardiograms, and clinical laboratory safety tests were reported as AEs.	Day 1 until the end of study (or primary data cut-off date for ongoing participants); median [min, max] duration was 5.57 [1.5, 13.7] months
Maximum Observed Plasma Concentration (Cmax) of Sotorasib	Pharmacokinetic (PK) parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.	Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Days 1 and 8
Time to Achieve Cmax (Tmax) of Sotorasib	PK parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.	Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Days 1 and 8
Area Under the Plasma Concentration-Time Curve From Time 0 to 24 Hours (AUC0-24h) of Sotorasib	PK parameters were determined from the concentration-time profile using standard non-compartmental approaches and considering the profile over the complete sampling interval.	Pre-dose and 0.25, 0.5, 1, 2, 4, 6, and 24 hours post-dose on Days 1 and 8

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Objective Response (OR)	Measured by computed tomography (CT) or magnetic resonance imaging (MRI). Assessed per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 guidelines.	Day 1 until the end of study (approximately 12 months)
Duration of Response (DoR)	Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines.	Day 1 until the end of study (approximately 12 months)
Progression-free Survival (PFS)	Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines.	Day 1 until the end of study (approximately 12 months)
Disease Control Rate (DCR)	Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines.	Day 1 until the end of study (approximately 12 months)
Time to Response (TTR)	Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines.	Day 1 until the end of study (approximately 12 months)
Duration of Stable Disease	Measured by CT or MRI. Assessed per RECIST version 1.1 guidelines.	Day 1 until the end of study (approximately 12 months)

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): April 28, 2020
• Primary Completion (Actual): December 31, 2021
• Study Completion (Estimated): July 15, 2024

Study Registration Dates

• First Submitted: May 6, 2020
• First Submitted That Met QC Criteria: May 7, 2020
• First Posted (Actual): May 8, 2020

Study Record Updates

• Last Update Posted (Actual): March 22, 2024
• Last Update Submitted That Met QC Criteria: September 12, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Keywords: Advanced Solid Tumors; KRAS p.G12C Mutation; AMG510 phase 1; Chinese Descent
• Additional Relevant MeSH Terms: Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Sotorasib
• Other Study ID Numbers: 20190147

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 (or other new use) 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, and if not approved, may be further arbitrated by a Data Sharing Independent Review Panel. 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 link 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
• product manufactured in and exported from the U.S.: Yes