This trial hypothesizes that adding anti-angiogenesis therapy to anti-PD1 therapy will reverse PD1 resistance and improve response to immunotherapy with immune checkpoint inhibitors in patients with recurrent endometrial cancer with deficient mismatch repair system. All patients enrolled will receive pembrolizumab as standard of care combined with Sitravatinib, which will be self-administered orally daily at 100 mg. Treatment will continue until disease progression or unacceptable toxicities. For patients with a complete response to therapy, maintenance therapy with both drugs will be continued for 12 months after achieving complete response. The combination of pembrolizumab with sitravatinib is an attractive treatment approach for this patient population. Sitravatinib is an orally-available, potent small molecule inhibitor of a closely related spectrum of receptor tyrosine kinases (RTKs) including MET, Axl, MERTK, VEGFR family, PDGFR family, KIT, FLT3, Trk family, RET, DDR2, and selected Eph family members. In addition to the immunostimulatory effects of Axl and MET inhibition, sitravatinib may further condition the TME in favor of antitumor activity by its immunomodulatory effects mediated through VEGFR and KIT inhibition.
This is a study of pembrolizumab in combination with sitravatinib in adult women with recurrent endometrial cancer or other solid tumors with deficient mismatch repair system. All patients enrolled will receive pembrolizumab as standard of care combined with Sitravatinib, which will be self-administered orally daily.