A phase 1 study evaluating preliminary safety, pharmacokinetic and pharmacodynamic of pemigatinib in Chinese patients with advanced malignancy.

Abstract

e15051 Background: Dysregulation of fibroblast growth factor receptor (FGFR) is strongly associated with establishment and progression of cancer. Pemigatinib is a selective FGFR1–3 inhibitor that are active in a targeted manner against cancers with activated FGFR pathway. The study was aimed at evaluating the tolerability, pharmacokinetic (PK) and pharmacodynamic (PD) of pemigatinib in Chinese patients (pts) with advanced malignancy. Moreover, potential efficacy of pemigatinib was explored in a broad spectrum of FGFR alteration in variety of cancer types. Methods: In this phase 1 study, Chinese patients with advanced, recurrent or metastatic malignancy that were histologically or cytologically confirmed and harboring FGF/ FGFR 1-3 variation were enrolled. Pemigatinib was self-administered orally at 13.5 mg QD on a 3-week cycle (2-weeks-on/1-week-off schedule). Adverse events and other safety factors were monitored throughout the study. Blood samples were obtained at prespecified time points for PK and PD analysis and efficacy was assessed every 9 weeks per RECIST v1.1 guideline. Results: As of Jan 31, 2021, 12 patients with 5 different cancer types (colorectal cancer (4 pts), gastric and gastroesophageal junction carcinoma (3 pts), cholangiocarcinoma (2 pts), esophageal carcinoma (2 pts) and breast cancer (1pts)) were enrolled. Documented FGF/ FGFR1-3 alterations were FGFR amplification (6), FGFR point mutation (5), FGFR2 fusion (2) and FGF alteration (4) with 2 subjects had more than one alteration types. All the subjects were failed to at least 1 line of prior standard therapy. All patients had at least 1 treatment related adverse events (TRAE) and the most common ones were hyperphosphatemia (100%), decreased appetite (50%) and diarrhea (33.3%). Two patients (16.7%) reported ≥ grade 3 TRAEs, which were hyponatremia (8.3%) and proteinuria (8.3%). There were no TEAEs leading to death or treatment discontinuation. Among 11 efficacy evaluable patients, 2 of them had partial responses (PR) as evaluated by investigators with 1 cholagiocarcinoma harboring FGFR2 point mutation (p.F276C) and the other esophageal carcinoma carrying FGFR1 mutation (p.A354V). 3 patients had a best overall response of stable disease (SD). The objective response rate (ORR) was 16.7% (95%CI: 2–48%) and disease control rate was 41.7% (95%CI: 15–72%). Conclusions: Pemigatinib had an acceptable and manageable toxicity and demonstrated a possible anti-cancer benefit in Chinese patients with advanced malignancy that accompanied with FGF/FGFR1-3 aberrance. A significant implication of the data is that it extended the population that potentially benefit from pemigatinib other than FGFR2 fusion/rearrangement. Clinical trial information: NCT04258527.