Understanding resistance in KRAS-driven cancers

A Non-interventional, Non-treatment, Non-randomized, Single Coordinating Center, Decentralized Bio-specimen Collection Study in USA-based Adult Subjects With Acquired Resistance to KRAS Inhibitors

This study is trying to understand why some patients with KRAS G12C mutant cancers don’t respond to treatments and how to tailor future therapies to help them better.

Quick facts

• Study type: Observational
• Enrollment: 500 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Addario Lung Cancer Medical Institute (other)
• Locations: 1 site (Boston, Massachusetts)
• Trial ID: NCT05272423 on ClinicalTrials.gov

What this trial studies

This observational study aims to investigate the mechanisms of resistance in patients with KRAS G12C mutant cancers who are experiencing disease progression while on KRAS-targeting therapies. Participants will remotely consent and provide plasma samples for analysis using the FoundationOne® Liquid Biopsy Assay. The study will compare resistance mechanisms across different drugs and tumor types, with the goal of personalizing subsequent therapies based on the findings. Data will be collected from two cohorts: one currently progressing on treatment and another who has previously undergone resistance testing.

Who should consider this trial

Good fit: Ideal candidates are adults over 18 with advanced KRAS G12C positive cancer who are experiencing systemic progression on a KRAS-targeting therapy.

Not a fit: Patients who are not experiencing disease progression or those who have not been treated with a KRAS-targeting therapy may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to more personalized treatment options for patients with KRAS G12C mutant cancers.

How similar studies have performed: Other studies have shown promise in characterizing resistance mechanisms in cancer, but this specific approach using remote plasma NGS is relatively novel.

Eligibility criteria

Inclusion Criteria:

* Cohort 1A- Liquid Biopsy

  1. Participants older than 18 years old at the time of consent or age of majority for residential state.
  2. Demonstration of having advanced KRAS G12C positive cancer.
  3. Systemic progression (not CNS only progression) within the past 30 days, having previously been treated with a therapeutic, targeting the specific KRAS mutation.
  4. Patient must not have started a new line of therapy before signing the informed consent form.
  5. Willingness to provide a blood specimen prior to the initiation of a new line of treatment.
  6. Willingness to provide clinical and medical information to the study team as required.
  7. Ability to read, write and communicate in English.
  8. Ability to sign a web-based informed consent form.

Cohort 1B- Data Sharing

1. Participants older than 18 years old at the time of consent or age of majority for residential state.
2. Demonstration of having advanced KRAS G12C positive cancer.
3. Systemic progression (not CNS only progression) after being treated with a therapeutic targeting the specific KRAS mutation.
4. Patient must have prior tumor genotyping available (tissue or plasma) after progression on therapeutic targeting the specific KRAS mutation.
5. Willingness to provide clinical and medical information to the study team as required.
6. Ability to read, write and communicate in English.
7. Ability of the participant or legally authorized representative (LAR) to sign a web-based informed consent form.

Exclusion Criteria:

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

Where this trial is running

Boston, Massachusetts

• Dana-Farber Cancer Institute — Boston, Massachusetts, United States (RECRUITING)

Conditions: KRAS P.G12C