First Patient Dosed in Phase 1b Trial of Sitravatinib-Tislelizumab Combo for Advanced Solid Tumors

First Patient Dosed in Phase 1b Trial of Sitravatinib-Tislelizumab Combo for Advanced Solid Tumors

A Phase 1b clinical trial studying a combination of Mirati Therapeutics‘ small molecule inhibitor sitravatinib and BeiGene‘s immune checkpoint inhibitor tislelizumab has begun dosing patients.

The open-label, multicenter trial (NCT03666143), expected to include 100 patients with advanced ovarian, lung, and kidney cancers, is being conducted in China and Australia. It is part of a collaboration between Mirati and BeiGene.

“We’re excited to move into the next phase of our collaboration with BeiGene. BeiGene’s ability to rapidly enroll patients into this clinical trial has the potential to significantly expand and accelerate our development efforts for sitravatinib and provide access to additional patient populations,” Charles Baum, MD, PhD, president and CEO of Mirati, said in a press release. “This clinical trial also has the potential to provide proof of concept clinical data in multiple solid tumor types.”

Sitravatinib is an inhibitor of tyrosine kinase receptors, essential players in multiple cell processes, including cell proliferation, differentiation, cell death, and cell-to-cell communication. Specifically, the molecule is a potent inhibitor of TAM family receptors and split family receptors, and is thought to disrupt the immunosuppressive environment of certain tumors, enhancing anti-tumor immune responses.

Sitravatinib is believed to work well in combination with immune checkpoint inhibitors, and is already being studied in combination with the PD-1 inhibitor Opdivo (nivolumab) in head and neck (NCT03575598), urothelial (NCT03606174), and kidney cancers (NCT03680521).

This Phase 1b trial is now testing sitravatinib with Beigene’s investigational PD-1 inhibitor, tislelizumab, which has been showing promise in non-small cell lung cancer (NSCLC) and urothelial cancer.

It will include patients with advanced or metastatic tumors, including non-squamous NSCLC, renal cell carcinoma (RCC), and ovarian cancer. Patients will receive 120 mg of oral sitravatinib once daily and 200 mg of tislelizumab injected into the blood once every three weeks.

Specifically, the trial will include five groups each with approximately 20 patients: NSCLC patients who failed prior PD-1/PD-L1 treatment, NSCLC patients who have never received PD-1/PD-L1 antibodies, RCC patients who failed prior PD-1/PD-L1 therapy, RCC patients who never received PD-1/PD-L1 treatment, and ovarian cancer patients who have never received PD-1/PD-L1 treatment and are resistant to platinum-based chemotherapy.

The trial’s primary objective is to assess the treatment’s safety, measured by the incidence of adverse events and serious adverse events. After the first six patients are enrolled at each site, patient recruitment will be on hold until the combination is deemed safe and well-tolerated.

“This collaboration has progressed quickly, and we are pleased that we can investigate the potential complementary activity of sitravatinib and tislelizumab in patients with advanced solid tumors in China and Australia,” said Amy Peterson, MD, chief medical officer of immuno-oncology at BeiGene.

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