A phase Ib/II single-arm study of cabozantinib plus dostarlimab in women with recurrent gynecologic carcinosarcoma

The multi-tyrosine kinase inhibitor cabozantinib has demonstrated modest activity alone or in combination with other agents in the treatment of endometrial cancer. While the efficacy of immunotherapy as single-agent therapy for gynecologic cancer has been limited, vascular endothelial growth factor (VEGF) inhibitors are thought to augment the therapeutic effects of immunotherapy by improving antigen presentation. Given the inhibitory effect of cabozantinib on VEGF as well as other targets important for tumor growth and invasion, it is hypothesized that the combination of cabozantinib with the immunotherapeutic agent dostarlimab will demonstrate efficacy in the treatment of recurrent gynecologic carcinosarcoma.

This prospective single-arm trial will enroll 37 patients. Patients with a histologically confirmed diagnosis of gynecologic carcinosarcoma who have received at least 1 prior chemotherapy regimen with measurable disease as defined by iRECIST are eligible. Patients must not have previously received cabozantinib, but prior immunotherapy is allowed. All patients will receive four 21-day cycles of 500 mg IV dostarlimab with 40 mg of daily oral cabozantinib. After 4 cycles, dostarlimab will be increased to 1000 mg and given on 42-day cycles and cabozantinib will continue to be a daily, oral medication at a dose of 40 mg. Treatment will continue until disease progression, unacceptable toxicity, withdrawal of consent, or until 2 years of therapy have been completed.

In the absence of effective treatments to prolong overall or progression-free survival, this innovative combination of therapies provides an opportunity to make significant improvements in outcomes following first-line therapy for patients with recurrent gynecologic carcinosarcoma.