Now Enrolling: ComboMATCH treatment trial E5 is testing a new option for patients with advanced solid tumors that have a KRAS G12C mutation

Another ECOG-ACRIN Cancer Research Group (ECOG-ACRIN) treatment trial has opened as part of the ComboMATCH precision medicine study platform. ComboMATCH is a set of clinical trials to study cancer treatment directed by genetic testing, rather than by cancer type (where the cancer first started in the body). Patients may be eligible if they have a tumor test result that shows they have one or more of the gene abnormalities being studied in the ComboMATCH trials. The first ECOG-ACRIN trial in ComboMATCH opened in July 2023, and there are currently seven approved treatment trials across the National Clinical Trials Network.

The new trial, ComboMATCH-E5, is studying a combination of two drugs in patients with advanced solid tumors that harbor the KRAS G12C mutation. The two drugs are sotorasib (pronounced SOH-tə-RAS-ib) and panitumumab (pan-i-TOO-moo-mab).

Sotorasib (brand name Lumakras^TM) is in a class of medications called KRAS inhibitors that work by blocking the action of the KRAS G12C mutation that causes cancer cells to multiply and spread. Sotorasib is approved by the FDA as a single therapy for patients with advanced non‒small cell lung cancer with the KRAS G12C mutation.

Panitumumab (brand name Vectibix®) is in a class of medications called monoclonal antibodies. It is approved by the FDA as a single therapy for adults with advanced colorectal cancer that has been tested and confirmed to be wild-type RAS.

Researchers are looking to find out whether these two drugs working together may kill more tumor cells in patients with KRAS G12C-mutated solid tumors than when the drugs are given alone. Prior research has found promising signs that this combination is effective in patients with KRAS G12C metastatic colorectal cancer. E5 is looking at the combination across a range of solid tumors.

Not all tumors with a KRAS G12C mutation respond to KRAS inhibitor drugs. Even those that do tend to quickly develop resistance to them. The E5 trial is studying whether sotorasib and panitumumab working in tandem may help to overcome this resistance.

Adults with a solid tumor harboring the KRAS G12C mutation and whose cancer has progressed on at least one prior therapy may be eligible for the E5 trial. Doctors aim to enroll a total of 105 patients; enrollment will be limited to 15 patients in a given solid tumor type to ensure that the trial includes multiple types of cancer. Patients must first enroll in the ComboMATCH registration trial (EAY191) to help determine eligibility. 

Participants in the E5 trial who have never received treatment with a KRAS G12C inhibitor will be randomly assigned by a computer to Group 1 or Group 2. Patients in Group 1 will take sotorasib as a once-daily pill for 28 days and have panitumumab administered intravenously on days 1 and 15 of each 28-day cycle. Patients in Group 2 will receive sotorasib only.

Those who have previously received a KRAS G12C inhibitor to treat their cancer will be assigned to Group 3 and also receive the sotorasib-panitumumab combination. Patients in Group 2 receiving sotorasib alone and whose cancer has progressed will be eligible to switch to Group 3 and receive the combination.

Patients may stay on treatment so long as the tumors shrink or remain stable, and they are able to tolerate any side effects. Patients will have imaging (CT scans or MRI) before, during, and after treatment to measure tumor size and thus monitor which tumors respond to—or resist—the combination treatment.

If this trial is successful, the positive results would be a strong signal that the combination should move on to a larger randomized phase 3 trial for confirmation outside of ComboMATCH.

This phase 2 treatment trial is led by Kristen Spencer, MD, of New York University Langone Perlmutter Cancer Center.

Learn more about EAY191-E5 at ecog-acrin.org.