On June 04, 2016 Five Prime Therapeutics, Inc. (Nasdaq:FPRX), a clinical-stage biotechnology company focused on discovering and developing innovative immuno-oncology protein therapeutics, reported that updated data from the ongoing Phase 1b trial of FP-1039/GSK3052230 (hereafter FP-1039) in mesothelioma patients were reported today in a poster presentation at the 2016 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting in Chicago (Press release, Five Prime Therapeutics, JUN 4, 2016, View Source [SID:1234512998]). Dr. Jose Trigo from the Hospital Universitario Virgen de la Victoria, Málaga, Spain, presented the poster, titled Multi-arm, open-label Phase 1b study of FP-1039/GSK3052230 with chemotherapy in malignant pleural mesothelioma (MPM). The poster is available on the Five Prime website: View Source

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The mesothelioma arm of the open-label Phase 1b trial evaluated weekly infusions of FP-1039, an FGF ligand trap, in combination with 1st-line pemetrexed and cisplatin in patients with untreated, unresectable MPM. Following the dose escalation portion of the trial, 15 mg/kg of FP-1039 was identified as the maximum tolerated dose (MTD) and established as the dose for expansion in patients with MPM. The primary study endpoints are safety and response rates, with Progression Free Survival (PFS), duration of response and translational measures as secondary endpoints. The poster includes data from 34 MPM patients who had received doses of FP-1039 as of the April 18, 2016 data cut-off and 18 patients were continuing on the trial at that time point.

Safety Data

The most common adverse events (AEs; all grades) observed were: nausea (53%), decreased appetite (41%) and fatigue (35%)
The vast majority of events were Grades 1-2
Three dose-limiting toxicities (DLTs) were reported at the 20 mg/kg dose (Grade 5 bowel perforation/ischemia, Grade 3 elevated creatinine level and Grade 3 infusion reaction) whereas no DLTs were reported at 15 mg/kg, and thus maximum tolerated dose (MTD) was established at 15 mg/kg
Toxicities associated with small-molecule FGFR inhibitors, such as hyperphosphatemia, retinal detachment and nailbed changes, have not been observed.
Efficacy Data
In the 18 patients evaluable as of April 18, 2016 who had received FP-1039 doses at or below the 15 mg/kg MTD:

Preliminary Objective Response Rate (ORR) was 39%, with a Disease Control Rate (DCR) of 100%, evaluated per mRECIST 1.1
7 confirmed Partial Responses (PRs) and 11 Stable Disease (SD)
Evaluable patients are defined as patients who enrolled at least 42 days (2 cycles) prior to the cutoff date, which was also the minimum time duration utilized in the calculation of DCR
Median Progression Free Survival (PFS) was 6.8 months, though the data are still maturing.
More than 50% (19 out of 34 dosed) of mesothelioma patients are still on trial
"The data continue to evolve and we are hopeful that FP-1039 will be shown to have potential benefit for patients with mesothelioma. Several mesothelioma patients were still on study at the time of the data cut off, so we will continue to follow their progress," said Lewis T. "Rusty" Williams, M.D., Ph.D., president and chief executive officer of Five Prime. "We are currently working with GSK to complete the trial and will be monitoring the quality and durability of patient responses and evaluating drug supply, manufacturing and other considerations as we determine the future plans for FP-1039."

About FP-1039
FP-1039 is a protein drug designed to intervene in FGF signaling. As a ligand trap, FP-1039 binds to FGF ligands circulating in the extracellular space (such as FGF2), preventing these signaling proteins from reaching FGFR1 on the surface of tumor cells. Treatment with FP-1039 treatment has not been shown to cause hyperphosphatemia, a side effect seen with small molecule inhibitors of FGF receptors, which block the activity of both cancer-associated FGFs and FGF-23. GlaxoSmithKline (GSK) is completing the ongoing Phase 1b trial in malignant pleural mesothelioma and will transfer its development and commercialization rights for FP-1039 back to Five Prime upon completion.