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

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

Scientific Rationale

Immunotherapies, including checkpoint inhibitors, are treatments that use the body’s own immune system to target and destroy cancer cells. Unfortunately, for many patients, immunotherapy treatments stop working over time. This is known as immunotherapy resistance.

Mirati is developing a medicine that may reverse immune suppression to enable the immune system to fight the disease. This approach includes targeting the TAM (TYRO3, AXL, MERTK) receptor family, which disables how tumor cells turn off the body’s immune response to attack cancer cells. Targeting these receptors creates a way for an immune response to occur, overcoming checkpoint inhibitor resistance.11,12

Unmet Need

Checkpoint inhibitors are not always effective. 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.13

Sitravatinib by the numbers:

Over 100,000 patients in the U.S. and EU taking checkpoint inhibitors needed 2nd line treatment for NSCLC in 2020.13

Around 70,000 of those patients had non-squamous NSCLC.13

Mechanism of Action

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

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

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.14

Sitravatinib in the Tumor Microenvironment

Watch our mechanism of action video

Program Summary

Sitravatinib is being evaluated in multiple clinical trials to treat patients who are resistant to immune checkpoint inhibitor therapy, as well as select patients who are naïve to 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

There is promising evidence that in combination with other immunotherapies, sitravatinib has the potential to provide long-term benefit to patients.