Sitravatinib

Sitravatinib is an investigational spectrum-selective kinase inhibitor that inhibits receptor tyrosine kinases (RTKs).

Scientific Rationale

Immunotherapies, including checkpoint inhibitors (CPI), are treatments that use the body’s own immune system to target and destroy cancer cells.

For many patients, immunotherapy treatments stop working overtime. This is known as immunotherapy resistance.

Mirati is developing a medicine that when combined with a CPI may help augment the antitumor response.

Sitravatinib may promote a more immunostimulatory tumor microenvironment and may combine with CPI to overcome resistance to prior CPI therapy.^13,14,15

Unmet Need

As many as 70% of patients with non-small cell lung cancer (NSCLC) do not respond to single-agent checkpoint inhibitor therapy or progress after single agent immunotherapy.

By the numbers:

Over 100,000 patients in the U.S. and EU taking checkpoint inhibitors needed 2nd line treatment for NSCLC in 2020¹²

~70,000 of those patients had non-squamous NSCLC¹²

Mechanism of Action

Sitravatinib is an investigational oral spectrum-selective kinase inhibitor. It potently inhibits receptor tyrosine kinases (RTKs), including:

TAM family receptors (TYRO3, AXL, MERTK)¹³
Split family receptors (VEGFR2, KIT)¹³

By targeting specific RTK receptors with sitravatinib, the immunosuppressive tumor microenvironment (TME) is converted to an immune-supportive TME. This way, cancers are more likely to respond to checkpoint inhibitor treatment.¹⁶

Tumor Microenvironment

Program Summary

Sitravatinib is being evaluated in multiple clinical trials to treat patients who are resistant to immune checkpoint inhibitor therapy.

Clinical trials include:

A registration-enabling Phase 3 clinical trial in combination with a checkpoint inhibitor in second or third line NSCLC patients

Combination clinical trials evaluating the impact of sitravatinib with checkpoint inhibitors for select checkpoint inhibitor naïve patients, including those with NSCLC or bladder cancer