From February 20, 2020 to July 2, 2020, 25 patients were screened; a total of 12 patients were enrolled and received treatment (median age of 61 years [range: 27–69], 7 [58.3%] males, 6 [50.0%] ECOG PS 1, 6 [50.0%] metastatic solid tumors), including 4 (33.3%) patients with CRC, 3 (25%) gastric/gastroesophageal junction carcinoma, 2 (16.7%) esophageal carcinoma, 2 (16.7%) CCA, and 1 (8.3%) breast cancer. Five (5/12, 41.7%) patients received ≥ 3 lines of prior systemic anti-cancer treatment. All patients harbored one or more types of FGF/FGFR1-3 alterations including FGFR1 amplification (4/12, 33.3%), FGFR2 point mutation (3/12, 25.0%), FGFR1 point mutation (2/12, 16.7%), FGFR2 amplification (2/12, 16.7%), FGFR2 fusion (2/12, 16.7%), FGF3 point mutation (1/12, 8.3%), FGF3 amplification (1/12, 8.3%), FGF4 amplification (1/12, 8.3%), and FGF19 amplification (1/12, 8.3%). The demographics and baseline characteristics were listed in Table 1.

As of the data cutoff date of March 8, 2021, all patients discontinued treatment due to disease progression. The median duration of treatment was 62 days (range: 35–246) with median treatment cycle of 3.0 (range: 2–12). All patients were in compliance with pemigatinib dosing regimen.

Twelve participants who received pemigatinib 13.5 mg daily on the intermittent schedule were assessed for PK on Cycle 1, Day 1 (C1D1) and Cycle 1, Day 14 (C1D14), respectively. Figure 1 presents pemigatinib concentration over time after dosing of pemigatinib during C1D1 and C1D14 (steady state). A summary of the PK parameters of pemigatinib for C1D1 and C1D14 (steady state) are presented in Table 2.

Mean plasma pemigatinib concentration–time curve (Mean ± SE) after single-dose or multiple-dose administration in Chinese patients with advanced cancer. DOSE 1: Mean Plasma pemigatinib concentration–time curve (Mean ± SE) after first-dose at Cycle 1 Day 1; DOSE 14: Mean Plasma pemigatinib concentration–time curve (Mean ± SE) at Cycle 1 Day 14 (steady state)

Following daily administration of 13.5 mg pemigatinib, it attained peak plasma concentrations after a median tmax of approximately 1.52 h at C1D1 and 1.99 h at steady state. The geometric mean terminal elimination half-life was 11.3 h. The steady-state geometric mean Cmax and AUC were 215.1 nmol/L7 and 2636.9 h·nmol/L, respectively. The degree of drug accumulation was measured by the accumulation ratio, and its geometric mean value was 1.32.

PD characteristics were analyzed in 11 out of 12 patients (with 1 subject excluded due to lack of baseline serum phosphate data). The serum phosphate concentrations increased on days 8 and 15 of cycle 1 (mean: 2.25 mg/dL, CV% [percent coefficient of variation]: 31.3%) and decreased to baseline post 1 week intermission. During subsequent treatment, the serum phosphorus remained below or near the baseline levels.

Overall, confirmed partial response (PR) was observed in two patients per investigator assessments, including one patient with FGFR1-mutant (p.A354V) esophageal carcinoma and one with FGFR2-mutant (p.F276C) CCA (Fig. 2), which contributed to an ORR of 16.7% (95% confidence interval [CI], 2.1%–48.4%; Supplement Table S1). Additionally, three (3/12, 25.0%) patients achieved stable disease (SD), thus contributing to a DCR of 41.7% (95% CI, 15.2%–72.3%). As of the data cutoff, ten patients had progressed disease, one patient died due to disease progression 32 days after last dosing, and one patient was lost to follow-up. Median PFS was 2.1 months (95% CI, 1.5–6.2), with a median follow-up of 5.1 months (range, 1.5–9.3).

Tumor swimmer plot for all patients. Clinical response was evaluated using Response Evaluation Criteria in Solid Tumors v1.1 by investigators. Abbreviations: CRC, colorectal cancer; GC/GEJC, gastric or gastro-esophageal junction carcinoma; CCA, cholangiocarcinoma; EC, esophageal carcinoma; BC, breast cancer

All patients experienced TEAEs (Table 3), most frequently hyperphosphataemia (12/12, 100%), hyponatraemia (8/12, 66.7%), decreased appetite (6/12, 50.0%), hypoalbuminaemia (6/12, 50.0%), and anaemia (6/12, 50.0%). Three (3/12, 25.0%) patients had grade ≥ 3 TEAEs, including hyponatraemia, hypercalcaemia, gamma-glutamyltransferase increased, lipase increased, proteinuria, and arthralgia, each in one patient (1/12, 8.3%); two (2/12, 16.7%) patients experienced grade ≥ 3 treatment-related AEs. No serious TEAEs occurred. No TEAEs led to treatment interruption/discontinuation or death; one (1/12, 8.3%) patient had dose reduction due to proteinuria.

All patients experienced at least one sponsor-defined clinically-notable TEAE, all being grade 1 or 2 in severity, including hyperphosphatemia (12/12, 100%), hypophosphatemia (3/12, 25.0%), nail toxicity (2/12, 16.7%), nail disorder (2/12, 16.7%) and nail discolouration (1/12, 8.3%).