A Phase IB/II Study of Alectinib Combined With Cobimetinib in Advanced ALK-Rearranged (ALK+) NSCLC

This is a Phase I/II clinical trial. A Phase I clinical trial tests the safety of investigational drugs or new combinations of approved drugs. In addition, a Phase I study tries to define the appropriate dose of the investigational drugs to use for further studies. "Investigational" means that the drugs are being studied. Following the phase I study, additional participants will be enrolled to the Phase II component. The phase II component will test the safest doses of alectinib and cobimetinib (as identified in the Phase I component) in a larger group of patients.

The FDA (the U.S. Food and Drug Administration) has approved alectinib as a treatment option for this disease.

The FDA has not approved cobimetinib as a treatment for this specific disease. However, cobimetinib is approved for treatment of melanoma, another type of cancer.

Alectinib is an oral ALK inhibitor made by the pharmaceutical company Genentech. The term ALK inhibitor means that alectinib targets the abnormal ALK protein that is causing your lung cancer cells to grow. Alectinib has been tested in other clinical research studies and results show that the drug may help stop the growth and spread of ALK+ lung cancer cells.

Cobimetinib is an oral inhibitor of MEK, a signaling protein that can cause some types of lung cancer to grow. Cobimetinib is also made by Genentech. Laboratory studies suggest that ALK and MEK may work together to help ALK+ lung cancer cells grow. In the laboratory, combination treatment with drugs targeting ALK and MEK prevented lung cancer cells from growing. It is possible that combination treatment with alectinib and cobimetinib will work better than alectinib alone to control the spread of the cancer.

In this research study, the investigators are trying to determine whether the combination of alectinib and cobimetinib is safe and well tolerated. This study will help determine the doses of the drugs that should be used in the Phase II portion of this study. Another purpose of this study is to determine whether adding cobimetinib to alectinib is effective for treating lung cancer that has already stopped responding to alectinib alone. In order to help understand why the cancer may have stopped responding to alectinib and whether treatment with the two drugs effectively blocks growth signals, all participants in this study will have periodic blood collections and undergo multiple biopsies.