Treating Advanced Solid Tumors with a KRAS G12C Mutation Using Targeted Therapies Called RAS(ON) Inhibitors

About the Study

This study is testing two new investigational targeted drugs called RAS(ON) inhibitors to learn how safe they are and how well they may work in people with advanced or metastatic solid tumors that have a biomarker called a KRAS G12C mutation.

Researchers are studying these drugs:

• On their own, and
• Together as a combination

The study is also looking at how the drugs move through the body and whether tumors shrink or stop growing.

RAS(ON) inhibitors are oral targeted therapies designed to block a pathway called RAS, which plays a role in several types of  cancer. RAS(ON) inhibitors are not yet FDA‑approved and are only available through participation in a clinical trial. One  RAS(ON) inhibitor, known as daraxonrasib is available for some people with advanced pancreatic cancer through a program known as expanded access. You can read more about expanded access for daraxonrasib. 

What the Study Involves

All participants will receive one or both of the study drugs. This is an open label study, all participants will know which study drug they received. The study will enroll in two phases. 

• Phase 1 will be a dose-finding phase to determine the ideal dose. 
• Phase 2 will be a dose-expansion phase once the ideal dose is determined. 

Participants will be assigned to one of three groups and will receive one or both RAS(ON) inhibitors to be taken orally (by mouth) daily:

• Daraxonrasib alone
• Elironrasib alone
• Daraxonrasib and elironrasib in combination

This is an open‑label study, meaning participants and researchers know which treatments are being given. Treatment group will be determined based on: 

• The study phase (dose‑finding vs dose‑expansion).
• The specific group that is currently enrolling.
• The participant’s cancer type and prior treatments.

While participants are receiving daraxonrasib, elironrasib, or both, follow‑up care includes close monitoring by the study team, such as:

• Regular clinic visits.
• Blood tests to monitor safety, organ function, and drug levels.
• Physical exams and vital signs.
• Imaging scans (such as CT or MRI) to see whether tumors are shrinking, staying the same or growing.
• Ongoing monitoring and management of side effects.

Participants will receive the study drugs and remain on the study as long as the drugs are helping and side effects are manageable.

In order to participate, people must have the following:

• Diagnosed with an advanced or metastatic solid tumor that cannot be treated with surgery or radiation.
• Their cancer must have a biomarker known as a KRAS G12C mutation.
• Their cancer can be seen and measured on scans.
• They are able to take oral medication.
• They have good overall physical functioning.

See clinicaltrials.gov for full eligibility criteria. 

People with any of the following cannot join the study:

• Have active or untreated spread to the brain or central nervous system.
• Have any other conditions that may affect the ability to take or absorb the study drug.
• Had major surgery within the past 4 weeks.