FDA Approves Astellas’ Vyloy for Advanced Gastric and Gastroesophageal Junction Adenocarcinoma

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The FDA has approved Astellas Pharma’s Vyloy (zolbetuximab-clzb) in combination with chemotherapy for locally advanced unresectable or metastatic human epidermal growth factor receptor 2 (HER2)-negative gastric or gastroesophageal junction (GEJ) adenocarcinoma whose tumors are claudin (CLDN) 18.2 positive. According to the company, the treatment is the first CLDN18.2-targeted therapy for advanced GEJ adenocarcinoma to be approved by the FDA. The approval was based on results of the Phase III SPOTLIGHT and GLOW trials, which showed significant improvements in progression-free survival (PFS) and overall survival (OS).¹

“The approval of Vyloy as the first and only targeted therapy for CLDN18.2-positive patients in the US further delivers on our relentless pursuit of scientific progress for devastating diseases like gastric and GEJ cancers, which are often only discovered at the advanced stage. This achievement is the result of years of dedicated research and development focused on targeting a novel biomarker, and we are grateful to the patients, investigators, and Astellas team members who have made this important advancement for patients a reality,” said Moitreyee Chatterjee-Kishore, PhD, MBA, SVP, head, immune-oncology development, Astellas, in a press release.

The global, multi-center, double-blind, randomized SPOTLIGHT study assessed the efficacy and safety of Vyloy plus mFOLFOX6 compared to placebo plus mFOLFOX6 as a first-line treatment. The trial enrolled 565 patients at 215 study locations across the United States, Canada, the United Kingdom, Asia, Australia, Europe, and South America. The primary endpoint was PFS, with secondary endpoints including OS, objective response rate, duration of response, safety and tolerability, and quality-of-life parameters.

The multi-center, double-blind, randomized GLOW study assessed the efficacy and safety of Vyloy plus Capox compared to placebo plus Capox as a first-line treatment. This study included 507 patients at 166 locations, with the same primary and secondary endpoints as the SPOTLIGHT trial.

Results of the SPOTLIGHT trial found that the combination of Vyloy and mFOLFOX6 reduced the risk of progression or death by 24.9%, with a median PFS of 10.61 months and a 25% reduction in the risk of death.² In the GLOW trial, Vyloy plus Capox demonstrated a 31.3% decrease in risk of progression or death and a median PFS of 8.21 months.³

In both trials, common treatment-emergent adverse events (AEs) were nausea, vomiting, and decreased appetite in the Vyloy arm;1 however, many of the same AEs were also reported in the placebo arm of both trials.^2,3

According to Beaumont Health, adenocarcinoma can occur in many different organs or parts of the body, including the colon, breasts, prostate, pancreas, esophagus, or lungs, and is the most common form of cancer in a number of these cancers. Ninety-nine percent of all prostate cancers, 85% of all pancreatic cancers, and 40% of all lung cancers are adenocarcinomas. It forms in glands that secrete mucus.⁴

“While there have been advances in the first-line treatment of locally advanced unresectable and metastatic gastric and GEJ cancers in the last several years, there is still a tremendous unmet need among our patients. The approval of Vyloy, based on the pivotal Phase III SPOTLIGHT and GLOW trials, brings forward a novel biomarker and new therapy for patients whose tumors are CLDN18.2 positive, and for those on the frontlines of treatment decision-making,” said Samuel J. Klempner, MD, associate professor, Harvard Medical School, medical oncologist, Massachusetts General Hospital, Boston, in the press release.

References

1. Astellas’ VYLOYTM (zolbetuximab-clzb) Approved by U.S. FDA for Treatment of Advanced Gastric and GEJ Cancer. Astellas. October 21, 2024. Accessed October 21, 2024. https://www.astellas.com/en/news/29291

2. Astellas to Present Positive Findings from Phase 3 SPOTLIGHT Trial of Zolbetuximab during 2023 ASCO GI Cancers Symposium. Astellas. January 19, 2023. Accessed October 21, 2024. https://www.astellas.com/en/system/files/news/2023-01/20230120_en_1.pdf?utm_source=press_release&utm_medium=pr%20&utm_campaign=us_vyloy_approval

3. Astellas Announces Positive Findings from Phase 3 GLOW Trial of Zolbetuximab during March ASCO Plenary Series. Astellas. March 22, 2023. Accessed October 21, 2024. https://www.astellas.com/en/system/files/news/2023-03/20230322_en_2.pdf?utm_source=press_release&utm_medium=pr%20&utm_campaign=us_vyloy_approval

4. Adenocarcinoma. Corewell Health. Accessed October 21, 2024. https://www.beaumont.org/conditions/adenocarcinoma#:~:text=Adenocarcinoma%20is%20the%20most%20common,women%20who%20have%20never%20smoked