Phase 2 FIGHT Trial Results Presented at ASCO GI Validate Importance of FGFR2b Overexpression and Reinforce Potential of Bemarituzumab Plus Chemotherapy as a Frontline Targeted Treatment for FGFR2b+ Gastric and GEJ Cancers
SOUTH SAN FRANCISCO, Calif.: Five Prime Therapeutics, Inc. has announced clinical results from 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. Trial results were presented in a late-breaking oral presentation today by UCLA Health’s Zev Wainberg, M.D., at the 2021 ASCO Gastrointestinal Cancers Virtual Annual Symposium (ASCO GI). The ASCO GI presentation slides are available on the company’s website.
The FIGHT trial evaluated 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.
“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.”
Phase 2 FIGHT Trial: Summary of Efficacy*
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Control Arm Placebo + mFOLFOX6 |
Investigational Arm Bema + mFOLFOX6 |
Statistical Measures |
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Median PFS, months |
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All patients (n=155) |
7.4 |
9.5 |
HR (95% CI): 0.68 (0.44, 1.04); p=0.073 |
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IHC 2+/3+ ≥ 5% (n=118) |
7.3 |
10.2 |
HR (95% CI): 0.54 (0.33, 0.87) |
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IHC 2+/3+ ≥ 10% (n=96) |
7.3 |
14.1 |
HR (95% CI): 0.44 (0.25, 0.77) |
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Median OS, months |
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All patients (n=155) |
12.9 |
Not Reached |
HR (95% CI): 0.58; (0.35, 0.95); p=0.027 |
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IHC 2+/3+ ≥ 5% (n=118) |
12.5 |
Not Reached |
HR (95% CI): 0.52 (0.30, 0.91) |
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IHC 2+/3+ ≥ 10% (n=96) |
11.1 |
Not Reached |
HR (95% CI): 0.41 (0.22, 0.79) |
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ORR, % |
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ORR (Intent to Treat) |
33 |
47 |
Improved by 13.1% (p=0.106) |
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ORR (measurable disease at baseline) |
40 |
53 |
Improved by 13% |
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* All three efficacy endpoints in the FIGHT Phase 2 trial met pre-specified statistical significance (2-sided alpha of 0.20) |
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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.
Ocular events are common in therapies targeting FGFR and were also reported in the FIGHT trial. More patients in the FIGHT trial discontinued bemarituzumab compared to placebo due to an adverse event (34.2% vs 5.2%) and the majority of these patients (21 of 26 patients) discontinued due to an ocular event.
The discontinuation of bemarituzumab due to an ocular event decreased the median duration of exposure to bemarituzumab by 3.2 weeks; from 25.3 weeks (n=55, range: 2.0 to 71.7 weeks) to 22.1 weeks (n=21, range: 12.0 to 46.7 weeks).
In designing the Phase 3 trial, the company plans to incorporate findings from the FIGHT trial including baseline eye exams, prophylactic lubricating eye drops and close monitoring for signs and symptoms of corneal toxicity, including dry eye.
