Clinical Trials

Date: 2018-09-10

Type of information: Completion of the trial

phase: 1-3

Announcement: completion of the trial

Company: Five Prime Therapeutics (USA - CA)

Product: FPA144 (bemarituzumab) in combination with mFOLFOX6

Action mechanism:

• monoclonal antibody. Bemarituzumab is a first-in-class, isoform-selective, humanized monoclonal antibody in clinical development as a targeted immunotherapy for tumors that overexpress FGFR2b, a splice variant of a receptor for some members of the fibroblast growth factor (FGF) family. Bemarituzumab blocks FGFs 7, 10 and 22 from binding to FGFR2b, and has been engineered for enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) to increase direct tumor cell killing by recruiting natural killer (NK) cells. Clinical results to date suggest that the specificity of bemarituzumab avoids the dose-limiting toxicities that have been seen with less selective pan-FGFR tyrosine kinase inhibitors that act on multiple FGFRs, including FGFR2.
• The antibody is being evaluated as a potential treatment for gastric cancer and bladder cancer. An estimated 10% of patients with gastric cancer have tumors that overexpress FGFR2b or have FGFR2 gene amplification, which is associated with poor prognosis.   
• In December 2017, Five Prime and Zai Lab announced a strategic collaboration for the development and commercialization of bemarituzumab in Greater China.

Disease: previously untreated, advanced gastric or gastroesophageal cancer

Therapeutic area: Cancer - Oncology

Country: USA

Trial details:

• The open label Phase 1 portion of the trial will evaluate ascending doses of FPA144 in combination with the modified FOLFOX6 regimen (mFOLFOX6) to identify a recommended dose for Phase 3. (NCT03343301 )

Latest news:

• • On September 10, 2018, Five Prime Therapeutics announced that the company completed the Phase 1 safety lead-in portion and has initiated the Phase 3 portion of the FIGHT Phase 1/3 clinical trial of bemarituzumab (FPA144), an isoform-selective anti-FGF receptor 2b antibody, in combination with chemotherapy in patients with previously untreated, advanced gastric cancer (GC) or gastroesophageal junction (GEJ) cancer.
• The Phase 1 portion tested bemarituzumab doses of 6 mg/kg and 15 mg/kg in combination with modified FOLFOX6 (mFOLFOX6) with no overlapping toxicities identified.
• The randomized, controlled, double-blinded Phase 3 portion of the FIGHT trial will evaluate bemarituzumab plus mFOLFOX6 versus placebo plus mFOLFOX6 in approximately 550 patients with gastric cancer  or gastroesophageal junction cancer whose tumors overexpress FGFR2b. The Phase 3 trial will include approximately 250 sites in the U.S., Europe and Asia, including China, South Korea and Japan, where the incidence of gastric cancer is high. Zai Lab will manage the Phase 3 portion of the FIGHT trial in China. The primary endpoint of the FIGHT trial is overall survival (OS) with secondary endpoints of progression-free survival (PFS), objective response rate (ORR), safety and pharmacokinetic (PK) parameters.
• • On January 2, 2018, Five Prime Therapeutics announced that on December 27, 2017, the company initiated dosing in the Phase 1 portion of the FIGHT Phase 1/3 clinical trial  of FPA144, an isoform-selective anti-FGF receptor 2b antibody, in combination with chemotherapy in patients with previously untreated, advanced gastric or gastroesophageal cancer.
• The open label Phase 1 portion of the trial will evaluate ascending doses of FPA144 in combination with the modified FOLFOX6 regimen (mFOLFOX6) to identify a recommended dose for Phase 3. Endpoints include safety, tolerability, and pharmacokinetic and pharmacodynamics parameters. Approximately 21 patients with unresectable, locally advanced, or metastatic gastrointestinal cancer will be enrolled during the Phase 1 portion of the FIGHT trial. FGFR2 status will be tested retrospectively but is not a requirement for enrollment.
• This safety lead-in portion of the study is designed to support the Phase 3 portion of the trial, which Five Prime expects to transition to in mid-2018. Five Prime designed the randomized, controlled Phase 3 portion of the trial to serve as a global registrational study. The FIGHT trial will evaluate FPA144 plus mFOLFOX6 versus placebo plus mFOLFOX6 in approximately 550 patients with advanced gastric or gastroesophageal cancer whose tumors overexpress FGFR2b or have FGFR2 gene amplification. Five Prime will use immunohistochemistry and circulating tumor DNA tests to identify patients who would be eligible for inclusion in the trial. The primary Phase 3 endpoint is overall survival with progression free survival, objective response rate, and safety as secondary endpoints. The Phase 3 portion of the trial is expected to include sites in the U.S., Europe and Asia, including China and Japan, where the incidence of gastric cancer is high.

Is general: Yes