Updated results of the Phase 2 FIGHT trial (NCT03694522) investigating bemarituzumab in combination with chemotherapy alone in patients with FGFR2b-positive, HER2-negative frontline advanced gastric or gastroesophageal junction cancers (GEJ) was presented during the annual meeting of the American Society of Clinical Oncology (ASCO) taking place virtually from June 4-8, 2021.

ASCOThe new data includes median Overall Survival (OS), a secondary endpoint that was reached with longer follow-up, as well as additional analyses of patient subgroups.

With a median follow-up of 12.5 months, the addition of bemarituzumab to chemotherapy resulted in a median OS of 19.2 months versus 13.5 months for chemotherapy alone in all randomized patients (n=155, HR: 0.6; 95% CI: 0.38, 0.94). In an exploratory pre-specified subgroup analysis, in patients with >10% of tumor cells overexpressing FGFR2b by immunohistochemistry (IHC), the median OS for bemarituzumab was 25.4 months versus 11.1 months (n=96, HR: 0.41; 95% CI: 0.23, 0.74).

The incidence of all-grade adverse events was similar in the bemarituzumab plus chemotherapy and chemotherapy only arm of the study (100% versus 98.7%, respectively). The incidence of corneal adverse events was higher in the bemarituzumab plus chemotherapy arm versus the chemotherapy arm (all grade AEs 67.1% versus 10.4%), with dry eye reported as the most common corneal event (26.3%). The majority of the corneal adverse events were reversible.

“Gastric cancer is the fourth leading cause of cancer death globally and 30% of frontline HER2-negative gastric cancer patients have tumors that overexpress FGFR2b,” said David M. Reese, M.D., executive vice president of Research and Development at Amgen.

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“These updated results underscore the benefits that bemarituzumab plus chemotherapy may bring to patients who have been fighting this aggressive disease with chemotherapy alone,” he said.

“We now look forward to advancing bemarituzumab into Phase 3 development,” he concluded.

More than one million new gastric cancer cases are diagnosed annually, and gastric cancer is particularly prevalent in Asia. [1][2]

Approximately 80 to 85% of advanced gastric and GEJ cancers are HER2-negative, and approximately 30% of these tumors overexpress FGFR2b. [3][4][5]

“These updated results further validate our work on the role of FGFR2b overexpression in gastroesophageal cancer and demonstrate that treatment with bemarituzumab in combination with chemotherapy can deliver a clinically significant reduction in the risk of disease progression for patients whose tumors overexpress FGFR2b,” said Daniel V.T. Catenacci, MD, Ph.D., medical oncologist and principal investigator at the University of Chicago.

Breakthrough therapy
Bemarituzumab (anti-FGFR2b) is a potential first-in-class, investigational targeted antibody that is designed to block specific fibroblast growth factors (FGFs) from binding and activating FGFR2b, inhibiting several downstream pro-tumor signaling pathways and potentially slowing cancer progression. Bemarituzumab is being developed in gastric and GEJ cancer as a targeted therapy for tumors that overexpress FGFR2b.

In April 2021, bemarituzumab was granted Breakthrough Therapy Designation by the U.S. FDA based upon a subset of patients from the FIGHT trial who showed at least 10% of tumor cells overexpressing FGFR2b.

Scientists at Amgen continue to investigate the role of FGFR2b and will continue to work with regulatory agencies on the next steps, including Phase 3 development, to bring this potential first-in-class therapy to patients.

Clinical trials
A Study of Bemarituzumab (FPA144) Combined With Modified FOLFOX6 (mFOLFOX6) in Gastric/Gastroesophageal Junction Cancer (FIGHT) – NCT03694522

[1]Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2018 Nov;68(6):394-424. doi: 10.3322/caac.21492. Epub 2018 Sep 12. Erratum in: CA Cancer J Clin. 2020 Jul;70(4):313. PMID: 30207593.
[2] Rawla P, Barsouk A. Epidemiology of gastric cancer: global trends, risk factors and prevention. Prz Gastroenterol. 2019;14(1):26-38. doi: 10.5114/pg.2018.80001. Epub 2018 Nov 28. PMID: 30944675; PMCID: PMC6444111.
[3] Shitara K, Bang YJ, Iwasa S, Sugimoto N, Ryu MH, Sakai D, Chung HC, Kawakami H, Yabusaki H, Lee J, Saito K, Kawaguchi Y, Kamio T, Kojima A, Sugihara M, Yamaguchi K; DESTINY-Gastric01 Investigators. Trastuzumab Deruxtecan in Previously Treated HER2-Positive Gastric Cancer. N Engl J Med. 2020 Jun 18;382(25):2419-2430. doi: 10.1056/NEJMoa2004413. Epub 2020 May 29. PMID: 32469182.
[4] Wainberg ZA, Enzinger PC, Kang YK, Yamaguchi K, Qin S, Lee KW, Oh SC, Li J, et al. Randomized double-blind placebo-controlled phase 2 study of bemarituzumab combined with modified FOLFOX6 (mFOLFOX6) in first-line (1L) treatment of advanced gastric/gastroesophageal junction adenocarcinoma (FIGHT). Presented at: ASCO Gastrointestinal Cancer Symposium; held January 15-16, 2021; Online Virtual Scientific Program (Abstract LBA160 and oral presentation).
[5] Catenacci DVT, Kang YK, Saeed A, Yamaguchi K, Qin S, Lee KW, Kim IH, et al. FIGHT: A randomized, double-blind, placebo-controlled, phase II study of bemarituzumab (bema) combined with modified FOLFOX6 in 1L FGFR2b+ advanced gastric/gastroesophageal junction adenocarcinoma (GC). Abstract: 4010; Presented at: American Society of Clinical Oncology (ASCO), held June 4 – 8, 2021.J Clin Oncol 39, 2021 (suppl 15; abstr 4010)

Featured image: General views of the 55th Annual Meeting of the American Association of Clinical Oncology (ASCO) – held in the McCormick Place in Chicago, Ill. Photo Courtesy: © 2019 ASCO/Max Gersh. Used with permission.

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