Studying Pathways of Resistance in KRAS-driven Cancers

NCT05272423 | Active Not Recruiting

• 1 other identifier: ALCMI-016
• Study Type: observational
• Target: 500
• Locations: 1 country
• Sites: 1

Brief Summary

Up to 250 patients from anywhere in the United States can remotely consent and participate to have plasma drawn locally and submitted to Foundation Medicine, Inc. (FMI), for the FoundationOne® Liquid Biopsy Assay. Patients who have had resistance mechanisms determined through other assays can also consent to share these data. The Investigator(s) will compare mechanisms of acquired resistance across drugs (e.g. sotorasib vs adagrasib) and between tumor types (e.g. NSCLC vs CRC) to determine if different resistance mutations arise in these settings.

Conditions

KRAS P.G12C

Outcome Measures

Primary Outcomes (1)

• Genomic mechanisms of acquired resistance to KRAS inhibitors

  The Investigator(s) will summarize mechanisms of acquired resistance with descriptive statistics (percentage and confidence interval), and compare across drugs (e.g., sotorasib vs adagrasib) and between tumor types (e.g., NSCLC vs CRC) to determine if different resistance mutations arise in these settings, using Fisher's exact test.

  up to 24 months follow-up

Study Arms (2)

Cohort 1A

Patients who are currently progressing on a KRAS G12C inhibitor. Plasma for ctDNA analysis will be collected.

Diagnostic Test: FoundationOne® Liquid CDx

Cohort 1B

Patients who have already had a sequencing assay performed to determine the resistance mechanism to a KRAS G12C inhibitor. These patients will be invited to share their data and medical history. Plasma for ctDNA analysis will be optional.

Diagnostic Test: FoundationOne® Liquid CDx

Interventions

FoundationOne® Liquid CDx DIAGNOSTIC_TEST

The FoundationOne® Liquid CDx is an FDA-approved companion diagnostic that analyzes guideline-recommended genes from a simple blood draw.

Cohort 1A; Cohort 1B

Eligibility Criteria

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

Study Population

Adult subjects with a diagnosis of acquired resistance to KRAS inhibitors

You may qualify if:

• Cohort 1A- Liquid Biopsy
• Participants older than 18 years old at the time of consent or age of majority for residential state.
• Demonstration of having advanced KRAS G12C positive cancer.
• Systemic progression (not CNS only progression) within the past 30 days, having previously been treated with a therapeutic, targeting the specific KRAS mutation.
• Patient must not have started a new line of therapy before signing the informed consent form.
• Willingness to provide a blood specimen prior to the initiation of a new line of treatment.
• Willingness to provide clinical and medical information to the study team as required.
• Ability to read, write and communicate in English.
• Ability to sign a web-based informed consent form.
• Cohort 1B- Data Sharing
• Participants older than 18 years old at the time of consent or age of majority for residential state.
• Demonstration of having advanced KRAS G12C positive cancer.
• Systemic progression (not CNS only progression) after being treated with a therapeutic targeting the specific KRAS mutation.
• Patient must have prior tumor genotyping available (tissue or plasma) after progression on therapeutic targeting the specific KRAS mutation.
• Willingness to provide clinical and medical information to the study team as required.

You may not qualify if:

• Participants who are unable to comply with the study procedures.
• Known existence of an uncontrolled intercurrent illness including, but not limited to, psychiatric illness or social situations that would impair compliance with study requirements.
• Participants who have previously enrolled to the study.

Sponsors & Collaborators

• Addario Lung Cancer Medical Institute: lead

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02215, United States

Location

Related Links

• SPARK study webpage

Biospecimen

Retention: SAMPLES WITH DNA

Whole blood; archival tissue (optional)

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 1, 2022
• First Posted: March 9, 2022
• Study Start: September 8, 2022
• Primary Completion: December 10, 2025
• Study Completion: March 1, 2026
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)