Abstract CT045: Phase 1, open-label, first-in-human study of AMG 900, an orally administered pan-aurora kinase inhibitor, in adult patients (pts) with advanced solid tumors
Authors: Shaheen Montasser , Markman Ben , Carducci Michael , Hurvitz Sara , Mahadevan Daruka , Kotasek Dusan , Goodman Oscar , Gamelin Erick , Chow Vincent , Juan Gloria , Rasmussen Erik , Friberg Gregory R. , Vogl Florian D. , Desai Jayesh 
Published: July 2016

Abstract
Purpose: Aurora kinases are associated with high proliferation, poor prognosis, and therapeutic resistance in several human tumor types. AMG 900 is an investigational, oral, highly potent, selective, pan-aurora kinase inhibitor. We evaluated the safety, tolerability, pharmacokinetics, and clinical activity of AMG 900 in pts with advanced solid tumors (NCT00858377).
Methods: In the dose escalation phase, eligible pts were ? 18 years old, with advanced solid tumors that were refractory to standard treatment, measurable disease per RECIST, ECOG ? 2, and life expectancy &gt; 3 months. In the dose expansion phase, eligible pts had taxane- and platinum-resistant epithelial ovarian cancer (OC), taxane-resistant triple-negative breast cancer (TNBC), or castration-resistant and taxane- or cisplatin-etoposide-resistant stage IV prostate cancer (CRPC). AMG 900 was administered 4 days on/10 days off at doses of 1 to 50 mg/day (dose escalation), and at the maximum tolerated dose of 40 mg/day with G-CSF support (dose-expansion). The primary objective was safety. Tumor response was determined per RECIST for all pts and additionally by GCIG CA-125 for pts with OC.
Results: Treatment-related AEs were reported by 98 of 105 pts (93.3%). Myelotoxicities were the most common grade ? 3 treatment-related AEs. In the dose escalation (N = 50), 1 pt with OC (30-mg cohort) had a partial response (PR) by RECIST and GCIG. In the dose expansion (N = 55), 3 of 29 pts (10.3%) with OC had a PR by RECIST, and 7 of 29 pts (24.1%) had a PR by GCIG; 72.4% of pts with OC had stable disease (SD), and the disease control rate (PR + SD) was 82.8%. Median (95% CI) duration of response in pts with OC per RECIST was 24.1 (16.1, 34.1) weeks, and median (80% CI) PFS was 31.1 (23.6, 34.1) weeks. See table for additional results.
Conclusions: AMG 900 had manageable toxicity with G-CSF support and promising single-agent activity in pts with heavily pretreated taxane- and platinum-resistant OC. Patient demographics, prior therapy, AEs, and best tumor responseDose escalation - advanced solid tumors (N = 50)OC (N = 29)TNBC (N = 14)CRPC (N = 12)Overall (N = 105)Male, n (%)21 (42.0)0 (0.0)0 (0.0)12 (100.0)33 (31.4)Female, n (%)29 (58.0)29 (100.0)14 (100.0)0 (0.0)72 (68.6)White or Caucasian, n (%)35 (70.0)23 (79.3)12 (85.7)11 (91.7)81 (77.1)Age, mean (SD), years56.5 (11.6)61.1 (11.4)54.6 (11.4)67.7 (8.0)58.8 (11.7)Prior lines of anti-cancer therapy, mean (SD)4.9 (3.2)5.3 (4.3)5.8 (3.0)4.5 (2.6)5.1 (3.4)Treatment-related AEs by preferred term (any grade), n (%)Fatigue21 (42.0)15 (51.7)6 (42.9)6 (50.0)48 (45.7)Neutropenia24 (48.0)14 (48.3)4 (28.6)4 (33.3)46 (43.8)Anemia15 (30.0)16 (55.2)6 (42.9)3 (25.0)40 (38.1)Nausea18 (36.0)10 (34.5)5 (35.7)5 (41.7)38 (36.2)Thrombocytopenia15 (30.0)11 (37.9)1 (7.1)2 (16.7)29 (27.6)Diarrhea14 (28.0)10 (34.5)1 (7.1)2 (16.7)27 (25.7)Alopecia13 (26.0)11 (37.9)1 (7.1)1 (8.3)26 (24.8)Decreased appetite11 (22.0)7 (24.1)2 (14.3)4 (33.3)24 (22.9)Vomiting9 (18.0)7 (24.1)5 (35.7)3 (25.0)24 (22.9)Leukopenia19 (38.0)3 (10.3)0 (0.0)1 (8.3)23 (21.9)Best tumor response - RECIST 1.1 criteria (central read), n (%)Complete response0 (0.0)0 (0.0)0 (0.0)0 (0.0)0 (0.0)Partial response1 (2.0)3 (10.3)0 (0.0)0 (0.0)4 (3.8)Stable disease29 (58.0)21 (72.4)7 (50.0)9 (75.0)66 (62.9)Progressive disease12 (24.0)3 (10.3)4 (28.6)1 (8.3)20 (19.0)Unable to evaluate8 (16.0)2 (6.9)3 (21.4)2 (16.7)15 (14.3)
Citation Format: Montasser Shaheen, Ben Markman, Michael Carducci, Sara Hurvitz, Daruka Mahadevan, Dusan Kotasek, Oscar Goodman, Erick Gamelin, Vincent Chow, Gloria Juan, Erik Rasmussen, Gregory R. Friberg, Florian D. Vogl, Jayesh Desai. Phase 1, open-label, first-in-human study of AMG 900, an orally administered pan-aurora kinase inhibitor, in adult patients (pts) with advanced solid tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr CT045.