Multicenter Phase 2 Study Of Nintedanib In Patients With Advanced Progressing Carcinoid Tumors

4105 Background: Serotonin is the cause of carcinoid symptoms and can signal the formation of fibroblasts via fibroblast growth receptors (FGFR). Nintedanib is an oral inhibitor of the FGFR pathway and several angiogenic signaling pathways thought to drive carcinoid tumor progression. We hypothesized that nintedanib may slow tumor progression in pts with progressing carcinoids in a phase 2 study. Methods: Thirty pts with unresectable/metastatic carcinoids on stable dose of somatostatin analogue for ≥3 months were included from two sites (NCT02399215). Primary Endpoint: progression free survival (PFS) rate at 16 wks. Secondary Endpoints: Objective response (complete + partial responses) using standard RECISTv1.1 criteria; overall survival (OS); change in QOL throughout treatment using EORTC QLQ–GI.NET21 questionnaire for carcinoid pts; and toxicity (graded using the NCI CTCAE version 4.0). Results: Baseline characteristics: M/F: 15/15), ECOG PS: 0/1/2: 11/17/2; Median age (years): 64.9 (45.1-77.2); site of origin: small bowel (13), colon (7), lung (4), gastric (1), unknown primary (5); PD on prior everolimus: 10/30 (30%). PFS rate at 16 wks was 86.7%; 95%CI: 72-95.3% (26 pts). The study was designed to compare to a historic PFS rate of 0.30 with everolimus. Kaplan Meier median PFS and OS estimates were 11 and 27.6 months, respectively, with 6 pts currently on active treatment. RECIST response: PR 1(4%), SD 20(83%), PD 2(8%), NE 1(4%). Reasons for coming off therapy: progression 14 (58%), toxicity 5(21%), other (17%), death due to disease 1(4%). QOL was maintained or improved in at least 50% of subjects while on therapy. Treatment was held in 7 pts (23%) due to AEs. Highest grade AEs: gr2 in 14(47%) and gr3 in 8(27%) pts. The most common gr 2 were GI (9), heme (8) and gr 3 were hypertension (6) and decreased appetite (2). From individual Bayesian analysis using the nintedanib pop PK model developed, correlation between actual and predicted exposures, with 61% variability in the absorption rate between pts was seen. Conclusions: Nintedanib is active and well tolerated in pts with advanced carcinoids. PFS data are encouraging and expected to mature. Ongoing biomarker studies may allow optimal pt selection. Clinical trial information: NCT02399215.