Study of Combination Therapy With the MEK Inhibitor, Cobimetinib, Immune Checkpoint Blockade, Atezolizumab, and the AUTOphagy Inhibitor, Hydroxychloroquine in KRAS-mutated Advanced Malignancies

Summary

This research study is for patients with an advanced cancer that carries a mutation in a gene called KRAS. Genes are parts of our DNA which carry instructions for a cell (the smallest component of an body part). In many cancers, the KRAS gene contains errors (mutations) which allows the tumors to grow. The purpose of this study is to determine if combination treatment with atezolizumab, cobimetinib, and hydroxychloroquine is safe, and if it will decrease the size of the tumor and prolong life in patients whose tumors contain this mutation. Cobimetinib and atezolizumab are both approved by the FDA for use in other cancers, but not in some cancer types being studied in this trial. Hydroxychloroquine is FDA approved to treat malaria and other conditions, but has also not been approved for these cancer types. Preliminary results have shown that this combination of drugs is effective at killing cancer cells and shrinking tumors in several KRAS-mutated cancers in animals.

Timeline

Start

2020-02-12

Primary completion

2022-04-11

Completion

2022-07-01

Publications

• Labadie BW, Obradovic A, Raufi AG, Wasko UN, Tomassoni L, Ge L, May M, Vij M, Li L, Ross I, Sedycius SS, Sender N, Dreher N, Wu L, Abuzaid S, Iuga A, Shah P, Wulfkuhle JD, Bates S, Wong W, Pellicciotta I, Lyashchenko AK, Safran H, Izar B, Petricoin EF, Cremers S, Tan AC, Lee S, Califano A, Olive KP, Manji GA. Targeting of MEK and Autophagy in Pancreatic Adenocarcinoma and Analysis of Treatment Sensitivity in Preclinical and Clinical Models: MEKiAUTO. JCO Precis Oncol. 2026 Jun;10(6):e2600138. doi: 10.1200/PO-26-00138. Epub 2026 Jun 12.

Drugs

Indications