Dr Van Tine on Investigating Cabozantinib With PD-1 and CTLA-4 Inhibition in Sarcoma

Brian A. Van Tine, MD, PhD, professor of medicine, Division of Oncology, Section of Medical Oncology, Washington University School of Medicine, Siteman Cancer Center, discusses the rationale for launching a randomized phase 2 trial (NCT04551430) investigating cabozantinib (Cabometyx) combined with nivolumab (Opdivo) and ipilimumab (Yervoy) vs cabozantinib alone in metastatic soft tissue sarcoma and discusses key findings from the trial.

Findings from the multicenter investigator-initiated trial were presented at the 2023 ASCO Annual Meeting, Van Tine begins. The rationale for this research can be traced back to findings from the randomized phase 2 A091401 trial (NCT02500797), which demonstrated activity with nivolumab with or without ipilimumab in patients with metastatic sarcoma, Van Tine explains. However, the development of this approach proved difficult due to the number of varying histologies in the sarcoma space. As such, investigators have been evaluating agents that can be added to immunotherapies to elicit a better response rate in patients with sarcoma, Van Tine adds.

VEGF plays an important role in enhancing the activity of immunotherapy, Van Tine expands. This led to the hypothesis that the addition of cabozantinib to combined checkpoint blockade may improve or prime for responses with the combination. As such, investigators allowed for cross over from the monotherapy arm to the combination arm upon progressive disease, Van Tine notes.

The primary end point of the trial was objective response rate, which has not been met yet at 11% (n = 7), Van Tine continues. Results from the trial demonstrated an 80% disease control rate (DCR) for patients treated with cabozantinib plus nivolumab and ipilimumab vs a 42% DCR in patients treated with cabozantinib alone (n = 36). In the control arm, disease control consisted of 2 partial responses and 11 cases of stable disease, Van Tine says, adding that these were both patients with leiomyosarcoma. Overall, the depth of response was greater with the triplet, Van Tine concludes.