Treating Advanced Solid Tumors with Targeted Therapies Called RAS(ON) Inhibitors Combined With the Targeted Immunotherapy Ivonescimab

About the Study

This study is testing whether combining a new type of targeted drug called RAS(ON) inhibitors with an immunotherapy drug called ivonescimab is safe and may help slow or shrink cancer in people with advanced or metastatic solid tumors that have a biomarker called a RAS mutation.

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 people with advanced pancreatic cancer through a program known as expanded access. You can read more about expanded access for daraxonrasib. 

Ivonescimab combines a type of immunotherapy called an immune checkpoint inhibitor with a type of targeted therapy known as a VEGF inhibitor that blocks the blood supply to tumors. Ivonescimab is not FDA-approved and is only available in the United States through participation in a clinical trial. 

What the Study Involves

Participants will receive one of the following RAS(ON) inhibitors to be taken orally (by mouth) daily:

• Daraxonrasib
• Elironrasib
• Zoldonrasib

Ivonescimab is given as an injection IV (into the vein).

Some participants may also receive additional cancer treatments, depending on their cancer type, such as:

• Platinum‑based chemotherapy with pemetrexed
• Cetuximab

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

This is an open‑label study, meaning participants and researchers know which treatments are being given.

In order to participate, people must have the following:

• Diagnosed with an advanced or metastatic solid tumor (such as lung or colorectal cancer).
• Their cancer must have a biomarker known as a RAS mutation (KRAS, NRAS, or HRAS).
• Their cancer can be seen and measured on scans.
• They are able to take oral medication.
• Good overall physical functioning.

Some parts of the study are for people who:

• Have already received standard treatments and their cancer progressed, or
• Have non‑squamous non‑small cell lung cancer with no other biomarkers with a targeted therapy option and have not yet received systemic treatment.

See clinicaltrials.gov for full eligibility criteria. 

People with any of the following cannot join the study:

• Have head or neck squamous cell cancer.
• Have a medical condition that could interfere with taking or absorbing oral medications.
• Have had major surgery within the past 4 weeks.