The first part of a Phase 2 trial investigating the AXL inhibitor bemcentinib in combination with Keytruda (pembrolizumab) in advanced non-small cell lung cancer (NSCLC) patients has completed enrollment of the planned 22 patients, BerGenBio announced.
Bemcentinib, formerly known as BGB324, is a small molecule that inhibits the AXL enzyme, which is a protein that helps cancer cells in two ways. First, it is an important regulator of the tumor cell capacity to migrate and invade other organs. Second, it is a key suppressor of anti-tumor immune responses, which allows cancer cells to resist and survive.
Preclinical studies have shown that bemcentinib enhances the effects of immune checkpoint inhibitors — such as anti-CTLA-4 and anti-PD-1 — in aggressive adenocarcinomas.
BerGenBio, in collaboration with Merck (or MSD outside the U.S. and Canada), is now designing an open-label Phase 2 trial (NCT03184571) testing bemcentinib with Keytruda in advanced NSCLC patients.
“We are encouraged by strong pre-clinical data combining bemcentinib with immune-therapy to increase and deepen responses as well as early clinical data suggesting that bemcentinib in combination with Keytruda has a favorable safety profile across several cancer indications,” Richard Godfrey, CEO of BerGenBio, said in a press release.
“This trial forms an important part in our strategy to provide proof of concept that selective AXL inhibition in combination with established and emerging cancer therapies may improve patient outcomes,” he said.
The study, taking place at more than 12 clinical sites across the U.S., U.K., Norway, and Spain, has two stages. First, 22 patients with previously treated NSCLC whose disease is progressing will receive the combination. Depending on the treatment’s safety and effectiveness in this group, another 26 participants might be enrolled.
Patients will receive 400 mg of bemcentinib orally in the first three days of treatment, which will then be tapered to 200 mg daily for the remainder of the trial. Keytruda will be given at a 200 mg dose every three weeks.
Investigators will evaluate the safety of the combination, along with patients’ anti-tumor activity and objective responses. They will also assess if certain biomarkers — including AXL and PD-L1 expression — can predict response to treatment.
The company is developing a diagnostic test that uses these and other biomarkers to identify patients who will likely benefit from a bemcentinib-Keytruda combination. Interim results from the Phase 2 trial are expected in 2018.
This combination is also being evaluated in triple-negative breast cancer patients in a Phase 2 trial (NCT031845580). In NSCLC, bemcentinib is also being tested with Tarceva (erlotinib) in a Phase 1/2 trial (NCT02424617) and with the chemotherapy Taxotere (docetaxel).
