First Patient Enrolled in Phase 1 Trial of INCB01158, Keytruda Combo for Solid Cancers

First Patient Enrolled in Phase 1 Trial of INCB01158, Keytruda Combo for Solid Cancers

The first patient has been treated in a Phase 1 clinical trial evaluating a combination of INCB01158 (aka CB-1158) plus Keytruda (pembrolizumab) in patients with advanced solid tumors.

The trial, sponsored by Calithera Biosciences, is evaluating the safety and effectiveness of INCB01158, given alone or in combination with an anti-PD-1 immune checkpoint inhibitor like Keytruda.

Developed by Calithera in collaboration with Incyte Corporation, INCB01158 is an immunotherapy that targets selectively the arginase enzyme.

“Arginase is involved in the metabolism of a key amino acid that is required for optimal anti-cancer immune function,” Susan M. Molineaux, PhD, founder, CEO, and president of Calithera Biosciences, said in a press release.

Arginase is an enzyme that is produced in the tumor microenvironment by immunosuppressive cells, like myeloid-derived suppressor cells (MDSCs). Its activity depletes the amino acid arginine, which is essential for immune T-cells to proliferate and survive.

Inhibiting arginase is thus expected to promote the T-cell expansion at the tumor site in cancers where arginase-secreting MDSCs are known to play an immunosuppressive role. These include renal cell cancer, breast cancer, lung cancer, and acute myeloid leukemia.

Because INCB01158 increases the amount of T-cells within the tumors, researchers believe it might work in synergy with other immunotherapies that unleash T-cells’ tumor-killing functions.

“In combination with an anti-PD1 therapy, an inhibitor of arginase may reduce immunosuppression caused by myeloid cells and broaden the reach of immuno-oncology therapies,” said Molineaux.

The Phase 1 trial (NCT02903914) is designed to assess the safety of INCB01158 and define a recommended dose to be used in planned Phase 2 studies, both as a monotherapy and in combination with immune checkpoint therapy.

The study is being conducted in the U.S. and is expected to include 236 patients with advanced or metastatic solid tumors. Enrollment is ongoing.

In an initial phase of the study, participants received increasing doses of the drug alone. After the optimal dose was selected, patients with advanced non-small cell lung cancer, colorectal cancer, and other solid tumors were included in monotherapy expansion groups.

Now, the investigators have started evaluating the safety of INCB01158 in combination with Keytruda. The recommended Phase 2 dose will be determined by testing up to six dose levels, ranging between 200 and 1,000 mg of oral INCB01158, along with the approved Keytruda dose and regimen.

This part of the study is designed to include patients with clear cell renal cell carcinoma, melanoma, non-small cell lung cancer, urothelial cell carcinoma, colorectal cancer, gastroesophageal cancer, squamous cell head and neck cancer, and mesothelioma.