Astellas Announces Zolbetuximab Meets Primary Endpoint in Phase 3 SPOTLIGHT Trial as First-Line Treatment in Claudin18.2 Positive, HER2-Negative Locally Advanced or Metastatic Gastric and Gastroesophageal Junction (GEJ) Cancers

• Astellas’ SPOTLIGHT trial meets primary endpoint of progression-free survival (PFS)
• Full data to be presented at future scientific congress

– Last week Astellas Pharma announced positive topline results from the Phase 3 SPOTLIGHT clinical trial evaluating the efficacy and safety of zolbetuximab in combination with mFOLFOX6 (a combination regimen that includes oxaliplatin, leucovorin and fluorouracil). Zolbetuximab is an investigational first-in-class monoclonal antibody targeting Claudin 18.2 (CLDN18.2), for the first-line treatment of patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction (GEJ) adenocarcinoma.

The SPOTLIGHT trial enrolled 566 patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or GEJ adenocarcinoma. The study met its primary endpoint showing statistical significance in progression-free survival (PFS) for patients treated with zolbetuximab plus mFOLFOX6 compared to placebo plus mFOLFOX6. In addition, the study met a secondary endpoint, overall survival (OS), showing statistical significance for patients treated with zolbetuximab plus mFOLFOX6 compared to placebo plus mFOLFOX6. The most frequent treatment-emergent adverse events (TEAEs) in patients treated with zolbetuximab plus mFOLFOX6 were nausea, vomiting, and decreased appetite. Detailed results will be presented at a future scientific congress and submitted for publication.

“The positive topline results from the SPOTLIGHT trial provides hope for patients with metastatic gastric and GEJ cancer. There are currently limited treatment options for this patient group. We have increased confidence in advancing development of zolbetuximab for the first-line treatment of patients with locally advanced or metastatic gastric cancer,” says Birgitte Claudius, Senior Medical Director at Astellas Nordics. “The topline results further support the role of CLDN18.2 as an emerging biomarker in gastric and GEJ cancer. The full results will be presented at a scientific congress in the near future.”

Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. In pre-clinical studies, this binding interaction then induces cancer cell death by activating two distinct immune system pathways — antibody-dependent cellular toxicity and complement-dependent cytotoxicity.¹ CLDN18.2 is a type of transmembrane protein found in normal gastric cells and is a major component of epithelial and endothelial tight junctions controlling the flow of molecules between cells.²Pre-clinical studies have shown that CLDN18.2, which can also be present in gastric tumors, may become more exposed and accessible to targeted therapies with antibodies as gastric tumors develop.^3,4,5 Based on this study, approximately 38% of screened patients have CLDN18.2-positive tumors, defined as CLDN18.2 expression in ≥75% of tumor cells with strong-to-moderate staining intensity based on a validated immunohistochemistry assay.⁶

The Phase 3 SPOTLIGHT trial is a global, multi-center, double-blind, randomized study assessing the efficacy and safety of zolbetuximab plus mFOLFOX6 compared to placebo plus mFOLFOX6. Specifically, this study and the Phase 3 GLOW trial, which is evaluating the efficacy and safety of zolbetuximab plus capecitabine and oxaliplatin (CAPOX) compared to placebo plus CAPOX, are being conducted to provide foundational data for regulatory submissions in the U.S., Europe, Asia and other countries globally.

Gastric cancer is often diagnosed in the advanced or metastatic stage, or once it has spread from the tumor’s origin to other body tissues or organs.⁷ The five-year relative survival rate for patients at the metastatic stage is approximately six percent.⁸

About Zolbetuximab

Zolbetuximab is an investigational, first-in-class chimeric IgG1 monoclonal antibody (mAb) that targets and binds to CLDN18.2, a transmembrane protein. Zolbetuximab acts by binding to CLDN18.2 on the cancer cell surface of gastric epithelial cells. In pre-clinical studies, this binding interaction then induces cancer cell death by activating two distinct immune system pathways — antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC).¹The safety and efficacy of zolbetuximab are under investigation in gastric, gastroesophageal and pancreatic cancers and have not been established. There is no guarantee the agent will receive regulatory approval or become commercially available for the uses being investigated.

About SPOTLIGHT Phase 3 Clinical Trial

SPOTLIGHT is a Phase 3, global, multi-center, double-blind, randomized study, assessing the efficacy and safety of zolbetuximab (IMAB362) plus mFOLFOX6 (combination regimen of oxaliplatin, leucovorin and fluorouracil) compared to placebo plus mFOLFOX6 as a first-line treatment of patients with CLDN18.2-positive, HER2-negative, locally advanced unresectable or metastatic gastric or gastroesophageal junction cancer. The study enrolled 566 patients at 220 study locations in the U.S., United Kingdom, Australia, Europe, South America and Asia. The primary endpoint is progression-free survival of participants treated with combination of zolbetuximab plus mFOLFOX6 compared to those treated with placebo plus mFOLFOX6. Secondary endpoints include overall survival, objective response rate, duration of response, safety and tolerability and quality-of-life parameters.

For more information, please visit clinicaltrials.gov under Identifier NCT03504397.

About Locally Advanced Unresectable Metastatic Gastric and Gastroesophageal Junction Cancer
Gastric cancer, also commonly known as stomach cancer, is the fifth most commonly diagnosed cancer
worldwide.⁹ Signs and symptoms can include indigestion or heartburn; pain or discomfort in the abdomen; nausea and vomiting; diarrhea or constipation; bloating of the stomach after meals; and loss of appetite and sensation of food getting stuck in the throat while eating.¹⁰ Signs of more advanced gastric cancer can include unexplained weight loss; weakness and fatigue; and vomiting blood or having blood in the stool.⁷ Risk factors associated with gastric cancer can include older age, male gender, family history, H. pylori infection, smoking and gastroesophageal reflux disease (GERD).^7,11 Because early-stage gastric cancer symptoms frequently overlap with more common stomach-related conditions, gastric cancer is often diagnosed in the advanced or metastatic stage once it has spread from the tumor’s origin to other body tissues or organs.⁷ The five-year relative survival rate for patients at the metastatic stage is approximately six percent.⁸ Gastroesophageal junction (GEJ) adenocarcinoma is a cancer that starts at the area where the esophagus joins the stomach.¹²

About Astellas

Astellas Pharma är ett företag som fokuserar på att förbättra människors hälsa runt om i världen genom att tillhandahålla innovativa och tillförlitliga läkemedel. Vi är främst verksamma inom sjukdomsområdena urologi, onkologi, transplantation, immunologi och nefrologi. Astellas vision är att ligga i framkant av vårdutvecklingen och skapa värde för patienter genom innovativ forskning och vetenskap. Med det nordiska huvudkontoret i Köpenhamn finns Astellas representerat i hela Norden. För mer information, besök vår hemsida www.astellas.se

För mer information kontakta

Birgitte Claudius, Senior Medical Director, Astellas Pharma, birgitte.claudius@astellas.com, +45 4343 0355

References

1. Sahin U, et al. FAST: a randomised phase II study of zolbetuximab (IMAB362) plus EOX versus EOX alone for first-line treatment of advanced CLDN18.2-positive gastric and gastro-oesophageal adenocarcinoma. Ann Oncol. 2021;32(5):609-19.

2. Sahin U, et al. Claudin-18 splice variant 2 is a pan-cancer target suitable for therapeutic antibody development. Clin Cancer Res. 2008;14(23):7624-34.

3. Niimi T, et al. Claudin-18, a novel downstream target gene for the T/EBP/NKX2.1 homeodomain transcription factor, encodes lung- and stomach-specific isoforms through alternative splicing. Mol Cell Biol. 2001;21(21):7380-90.

4. Türeci O, et al. A multicentre, phase IIa study of zolbetuximab as a single agent in patients with recurrent or refractory advanced adenocarcinoma of the stomach or lower oesophagus: the MONO study. Ann Oncol. 2019;30(9):1487-95.

5. Rohde C, et al. Comparison of Claudin 18.2 expression in primary tumors and lymph nodes metastases in Japanese patients with gastric adenocarcinoma. Jpn J Clin Oncol. 2019;49(9):870-6.

6. Data on file. Northbrook, Ill. Astellas Pharma Inc.

7. National Cancer Institute. Gastric cancer treatment (PDQ®): patient version (08-24-2021). Available at https://www.cancer.gov/types/stomach/patient/stomach-treatment-pdq. Last accessed November 16, 2022.

8. American Cancer Society. Stomach Cancer Survival Rates. Available at https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/survival-rates.html. Last accessed November 16, 2022.

9. Sung H, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2021;71(3):209-49.

10. American Cancer Society. Signs and symptoms of stomach cancer (01-22-2021). Available at

https://www.cancer.org/cancer/stomach-cancer/detection-diagnosis-staging/signs-symptoms.html. Last accessed November 16, 2022

11. American Cancer Society. Esophageal cancer risk factors (06-09-2020). Available at https://www.cancer.org/cancer/esophagus-cancer/causes-risks-prevention/risk-factors.html. Last accessed November 16, 2022.

12. American Cancer Society. About esophagus cancer (03-20-2020). Available at https://www.cancer.org/content/dam/CRC/PDF/Public/8614.00.pdf. Last accessed November 16, 2022.

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