Phase II study of cabozantinib and nivolumab in refractory metastatic microsatellite stable (MSS) colorectal cancer (CRC).

229 Background: Current data suggest that combining tyrosine kinase inhibitors with immune checkpoint inhibitors may be a promising treatment strategy in patients with metastatic MSS CRC. This prospective, open-label, single-arm, phase II study (NCT04963283) evaluated the efficacy of cabozantinib in combination with nivolumab in patients with metastatic refractory MSS CRC. Methods: Patients with metastatic/unresectable MSS CRC who were refractory to chemotherapy in the 3 rd line setting and beyond were eligible. Patients were treated with cabozantinib 40 mg orally daily and nivolumab 480 mg IV every 28 days. Tumor assessments were obtained every 8 weeks for the first 16 weeks, and then every 12 weeks thereafter. Response was assessed via RECIST v1.1. The primary endpoint was 16-week disease control rate (16-wk DCR); secondary endpoints were objective response rate (ORR), progression free survival (PFS), overall survival (OS), safety and tolerability, and correlative studies (to be presented at a future date). Results: Between June 2021 and January 2024, 49 pts were enrolled; 63% were male; median age 55 [50-64]. Median prior treatment regimens were 4 [2-14]. Most patients (84%) had not received prior trifluridine/tipiracil; only 1 patient had received prior regorafenib. The 16-wk DCR was 40% (19/47) (95% CI 0.264 – 0.557). The 16-wk ORR was 8.5% (4/47) (95% CI 0.024 – 0.204). mPFS was 3.4 months (95% CI 1.8-5.0) and mOS was 10.9 months (95% CI 4.7-13.8). Thirty nine percent of patients experienced a serious adverse event (SAE), with 4% Gr 1, 37% Gr 2, 35% Gr 3 and 4% Gr 4; there were no Gr 5 treatment related adverse events. The most common AEs were diarrhea (53%), fatigue (43%), hypothyroidism (31%), weight loss (29%), nausea (29%), and hypertension (27%). Two patients remain on study at time of abstract submission. Conclusions: The combination of cabozantinib and nivolumabwas well tolerated and provided modest benefit in a population of patients with metastatic, chemotherapy refractory, MSS CRC. Clinical trial information: NCT04963283 .