Abstract CT058: Phase I study of LY2874455, a fibroblast growth factor (FGF) receptor inhibitor, in patients with advanced cancer
Authors: Tie Jeanne , Bang Yung-Jue , Park Young Suk , Kang Yoon-Koo , Monteith David , Hartsock Kimberly , Hamid Oday , Thornton Donald E. , Michael Michael 
Published: July 2016

Abstract
Background: The fibroblast growth factor (FGF) and FGF receptor pathway has been implicated in several cancers. Inhibition of this pathway has led to the attenuation of tumor growth in preclinical models1. This phase I, first in human dose (FIH) study evaluated safety, tolerability, pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of LY2874455, an oral FGF receptor inhibitor.
Methods: This study had 2 open-label parts. Part A: standard 3+3 patient dose escalation study, identified 16 mg BID as the recommended dose2. Part B: dose expansion study, evaluated 16 mg BID dose in patients (pts) with pretreated advanced gastric cancer (GC) or non-small cell lung carcinoma (NSCLC), who also had ECOG performance status 0-2 and adequate organ function. Treatment continued until disease progression or intolerability. We report here results from Part B of the study.
Results: Overall 27 pts in the NSCLC cohort and 31 pts in the GC cohort were treated. Median age was 58.5 years: majority of pts were Asian (89.7%). Pts had received a median of 4 previous lines of chemotherapy. FGFR1 amplification status in the NSCLC group: 29.6% were negative, 7.4% were positive, and status was unknown in 63.0%. For GC pts: 80.6% negative for FGFR2 amplification, 6.5% positive, and status unknown in 12.9%. Both cohorts each received a median of 2 cycles. All 58 pts experienced at least 1 treatment emergent adverse event (TEAE) possibly related to study drug, with 39 pts (67.2%) experiencing at least 1 Grade 3 or 4 TEAE possibly related to study drug. The most common drug-related AEs included: hyperphosphatemia (79.3%), diarrhea (77.6%), anorexia (72.4%), and fatigue (51.7%). Eighteen pts (31.0%) experienced at least 1 serious adverse event (SAE), and 9 pts had SAE possibly related to study drug related. SAEs possibly related to study drug were: fatigue (n = 4), anorexia (n = 3), heamoptysis, central serous retinopathy, keratoconjunctivitis sicca, diarrhea, and hyponatremia. Eleven pts discontinued due to AE or SAE. In the GC cohort, 1 patient, who was FGFR2 amplification negative, had a partial response, and 6 FGFR2 negative pts had stable disease (SD), with 1 patient on treatment for 9 cycles. None of the NSCLC pts responded, but 4 pts had SD (FGFR1 positive n = 2; FGFR1 negative n = 2).
Conclusion: Treatment with LY2874455 had a manageable toxicity profile, and preliminary findings suggest anti-tumor activity in gastric cancer.
1. Hattori Y, Itoh H, Uchino S, Hosokawa K, Ochiai A, Ino Y, et al. Immunohistochemical detection of K-sam protein in stomach cancer. Clinical cancer research : an official journal of the American Association for Cancer Research. 1996;2:1373-81.
2. Tie, J., et al. “A phase I trial of LY2874455, a fibroblast growth factor receptor inhibitor, in patients with advanced cancer.” Proceedings of the 105th annual meeting of the American Association for Cancer Research 2014;74(19 Suppl):Abstract nr CT215.
Citation Format: Jeanne Tie, Yung-Jue Bang, Young Suk Park, Yoon-Koo Kang, David Monteith, Kimberly Hartsock, Oday Hamid, Donald E. Thornton, Michael Michael. Phase I study of LY2874455, a fibroblast growth factor (FGF) receptor inhibitor, in patients with advanced cancer. [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 CT058.