A multicenter phase II study of cabozantinib + nivolumab for patients (pts) with advanced angiosarcoma (AS) previously treated with a taxane (Alliance A091902).

• DOI: 10.1200/jco.2023.41.16_suppl.11503
• Publication Date: 2023-06-04T16:31:33Z
• Authors: Juneko E. Grilley...; Jacob B. Allred; Scott Schuetze; Elizabeth J. Davis; Michael J Wagner; Andrew Stewart Po...; Blake Waechter; Richard F. Riedel; Meng Xu WELLIVER; Stephanie A. Berg; Suzanne George; Steven Ian Robinson; Paul B. Googe; Sandra P. D'Angelo; Gary K. Schwartz
• Keywords: Cabozantinib; Taxane; Clinical endpoint

11503 Background: Collectively, sarcomas have demonstrated less benefit from immunotherapy than many other cancers. Pts with AS limited options, particularly after taxane chemotherapy. Although is a vascular malignancy, anti-VEGF therapies minimal monotherapy clinical activity. Some cutaneous high UV damage signature, but often do not. Cabozantinib (C) multikinase inhibitor that may alter PD-1 expression in regulatory T cells, promoting an immune permissive environment when combined nivolumab (N), fully human anti MAB. We hypothesize the combination of C+N will be effective therapy AS, across subtypes. Methods: This open-label multi-arm study enrolled pts locally advanced/metastatic AS. Arm 3, reported here, who had received for (including adjuvant) prior to enrollment. were not restricted on number lines, and immunotherapies allowed. Eligible C (40 mg po daily) N (480 IV every 4 wks). Treatment was permitted beyond progressive disease (PD) 1 st 12 wks (4 wk confirmatory scan), PD response censored at wks. The Simon 2-stage design (null alternative overall rate (ORR) 10% 35%, respectively) required ≥1 confirmed 9 stage, >4 18 (91.4% power, alpha 0.095) primary endpoint. Secondary endpoints adverse events (AEs), progression free, survival (PFS, OS), pt-reported outcomes (PRO). Results: 21 eligible [median age 66 yrs (32-92), 10 female] dose C+N. Primary sites: (scalp/face), liver, 2 breast, 6 other. All taxanes (11/21 = 52% as adjuvant therapy) 5/21 (24%) also anthracycline (all relapsed AS). endpoint: 13 first evaluable patients (72%) experienced objective (OR, 95%CI: 47%-90%). After median follow-up 11.2 mo, achieved OR (11 partial response, complete), ORR 62% (95%CI: 38-82%). Responses seen 7/12 (58%) noncutaneous 6/9 (67%). Median PFS 9.6 mo (5.3-NR), OS 20.5 (14.4-NR). Off treatment reasons include: (14), comorbid condition unrelated or (1); remain study. Grade (G) 3 hypertension only possibly related AE (TRAE) occurring ³10%. No G 4/5 TRAE reported. Conclusions: + significant antitumor activity taxane-pretreated well tolerated without new safety concerns. Activity PRO exploratory analyses are ongoing. Support: U10CA180821, U10CA180882, U24 CA196171; U10CA180820; https://acknowledgments.alliancefound.org . U10CA180868; U10CA180888. NCT04339738. Clinical trial information: NCT04339738