Five Prime Therapeutics’ Bemarituzumab Shows Promise in Phase 2 FIGHT Trial Against Gastric Cancers

Five Prime Therapeutics’ Bemarituzumab Shows Promise in Phase 2 FIGHT Trial Against Gastric Cancers

Five Prime Therapeutics (NASDAQ: FPRX) in partnership with Zai Lab Ltd. (Shanghai, China) recently shared the results of the global, randomized, double-blind placebo—controlled Phase 2 FIGHT trial evaluating first-in-class targeted therapy bemarituzumab in advanced gastric or gastroesophageal junction (GEJ) cancer. The trial results were recently presented by UCLA Health’s Zev Wainberg, MD, at the 2021 ASCO Gastrointestinal Cancers Virtual Annual Symposium (ASCO GI). The net findings included that those patients with untreated advanced gastric or gastroesophageal junction (GEJ) cancer lived longer than without disease progression with the addition of a fibroblast growth factor (FGFR) inhibitor to chemotherapy according to the data from the randomized trial.  Mean progression-free survival (PFS) increased from 7.4 months with chemotherapy alone to 9.5 months with bemarituzumab. The size of the PFS benefit increased with levels of FGFR2b expression. Median overall survival (OS) was 12.9 months with chemotherapy and not yet reached in patients who also received the FGFR1b inhibitor. 

The Challenge

Gastric cancer, also known as stomach cancer, is the third most common cause of cancer death worldwide and, excluding non-melanoma skin cancer, the fifth most common cancer worldwide, with over 1,000,000 new cases diagnosed each year. For HER2 negative patients, frontline therapy available today is the same systemic chemotherapy available since the 1990s

The Drug

Bemarituzumab (anti-FGFR2b) also known as (FPA144) is a first-in-class targeted antibody that is under development as a targeted therapy for tumors that overexpress FGFR2b. Designed to block tumor growth via two distinct mechanisms including 1) bind specifically to FGFR2b and prevent the binding of certain FGFs that promote tumor growth and 2) engineered to drive killing of tumor cells by antibody-dependent cell-mediated cytotoxicity via the recruitment of natural killer cells.

What is FGFR2b?

Called the fibroblast growth factor (FGF)/fibroblast growth receptor (FGFR) pathway is implicated in the development of cancer cells. FGFR2b is an FGFR found in epithelial cells, such as those in the stomach and skin. 30% of patients with HER2-gastric/gastroesophageal cancers overexpress FGFR2b. And FGFR2b is overexpressed in other cancers such as triple negative breast cancer, ovarian cancer, non-small cell lung cancer, and pancreatic cancer.

Deal with Chinese Biotech

This therapy came about due to a partnership inked in 2017 with a biotech firm in China named Zai Lab who now have the exclusive license to develop and commercialize the novel therapy in China, Hong Kong, Macau and Taiwan. As mentioned above, Zai Lab was a collaborating partner in the Phase 2 FIGHT trial in Greater China.

The Study

Targeting gastric cancer, the global, randomized, double-blind, controlled study (NCT03694522) evaluated the efficacy of Bemarituzumab and mFOLFOX6 (chemotherapy regimen) versus placebo and mFOLFOX6 in patients with FGFR2 selected Gastric Cancer (as determined by prospective IHC FGFR2b overexpression and /or a ctNDA blood assay demonstrating FGFR2 gene amplification). 

Known as the “FIGHT trial,” the study team investigated  bemarituzumab plus chemotherapy (mFOLFOX6) versus placebo plus chemotherapy in patients with fibroblast growth factor receptor 2b-positive (FGFR2b+), non HER2 positive frontline advanced gastric or GEJ cancer. The trial enrolled 155 patients in 15 countries across Asia, the European Union, and the United States, with 77 patients randomized to the bemarituzumab arm and 78 patients to the placebo arm.

The Phase 2 trial met all three efficacy endpoints and demonstrated statistically significant and clinically meaningful improvements in the primary endpoint of progression-free survival (PFS) and secondary endpoints of overall survival (OS) and overall response rate (ORR). Additional analysis showed a positive correlation between benefit and the percentage of FGFR2b+ tumor cells, confirming both the importance of the FGFR2b target and the activity of bemarituzumab against this target.

Adverse Events

The incidence of all grade adverse events was similar in the bemarituzumab and placebo arms of the study (100% vs 98.7%, respectively). Corneal events were reported more frequently in the bemarituzumab arm (67.1% vs 10.4%), with the most common corneal events in the bemarituzumab arm being dry eye (26.3%), keratitis (15.8%) and punctate keratitis (14.5%). Stomatitis (31.6% vs 13.0%) and elevated transaminases (34.2% vs 19.5%) were also more common in the bemarituzumab arm. Grade 3 and higher adverse events (82.9% vs 74.0%), serious adverse events (31.6% vs 36.4%) and deaths (6.6% vs 5.2%) were comparable across arms. For the remaining SAE data follow the link below.

Principal Investigator Point of View

“Systemic chemotherapy is the standard of care for this deadly and aggressive form of gastric cancer. We are strongly encouraged by these data and the potential for a frontline targeted treatment that can improve overall survival,” said Zev A. Wainberg, M.D., Associate Professor of Medicine at UCLA, Co-director of the Gastrointestinal Oncology Program and Director of Early Phase Clinical Research at the Jonsson Comprehensive Cancer Center. “The FIGHT trial results demonstrate that treatment with bemarituzumab in combination with chemotherapy can deliver a significant reduction in the risk of disease progression and death in gastric cancer patients whose tumors overexpress FGFR2b.”

“The Phase 2 FIGHT clinical trial results validate our pioneering work on the role of FGFR2b overexpression in gastric cancer, and we’re excited about the implications of this new scientific understanding for other cancers,” said Helen Collins, M.D., Five Prime’s Executive Vice President and Chief Medical Officer. “With these data in hand, we plan to continue to collaborate with regulatory agencies on next steps, initiate a global Phase 3 trial in gastric cancer and begin studying bemarituzumab in other epithelial cancers that overexpress FGFR2b.”

For more details on the results, including a detailed table, see the company’s press release.

Next Steps

The company announced 2021 priorities for the program which include collaboration with regulatory agencies on next steps, initiating a global Phase 3 trial in gastric and GEJ cancers and evaluating bemarituzumab in other epithelial cancers that overexpress FGFR2b.

About Five Prime Therapeutics

Five Prime is a clinical stage biotechnology company relentlessly focused on rewriting cancer. By tackling the tough scientific questions and untapped pathways, we aim to offer new hope by developing novel, breakthrough therapies that have potential to alter the course of disease in cancers with few treatment options. This vision is what defines us and guides our research, clinical development, and partnerships. To build a better tomorrow for people with cancer, we are teaming up with patients, physicians, scientists, and industry partners to make a meaningful difference in patients’ lives. Five Prime collaborates with leading global pharmaceutical companies and has therapies in pre-clinical and clinical development.

Lead Research/Investigator

Zev A. Wainberg, M.D., Associate Professor of Medicine at UCLA, Co-director of the Gastrointestinal Oncology Program and Director of Early Phase Clinical Research at the Jonsson Comprehensive Cancer Center.

Call to Action: Follow the link for the entire press release and more information.