AstraZeneca (NASDAQ: AZN) Phase III Sone-Ve data show gastric survival gain

Rhea-AI Filing Summary

AstraZeneca reported positive high-level Phase III results from the global CLARITY-Gastric01 trial, where sonesitatug vedotin (Sone-Ve) showed a statistically significant and highly clinically meaningful improvement in overall survival versus investigator's choice in 2nd and later-line CLDN18.2-positive advanced gastric, gastroesophageal junction and oesophageal adenocarcinoma cancers. The trial met a dual primary endpoint of overall survival in 3rd and later-line treatment and a key secondary endpoint of overall survival in the overall 2nd and later-line population, while progression-free survival showed an improvement trend but did not reach statistical significance.

Eligibility was based on CLDN18.2 expression in at least 25% of tumour cells, a threshold estimated to include about 60% of gastric/GEJ cancers and roughly 183,500 2nd and later-line patients annually in the US, EU, China and Japan. Sone-Ve was well tolerated with no new safety signals and is described as a potential first-in-class CLDN18.2-targeting antibody drug conjugate, supported by Orphan Drug Designation in the US and EU and Breakthrough Designation in China. AstraZeneca plans to present the data at a medical meeting and share them with global regulatory authorities.

Positive

• Sone-Ve significantly improves overall survival versus investigator's choice in 2nd and later-line CLDN18.2-positive advanced gastric/GEJ cancers in the Phase III CLARITY-Gastric01 trial.
• Large target population is implicated, with CLDN18.2 expression in 25% or more of tumour cells estimated in about 60% of gastric/GEJ cancers and roughly 183,500 2nd and later-line patients annually across the US, EU, China and Japan.
• Regulatory momentum is supported by Orphan Drug Designation in the US and EU for gastric and GEJ cancers and Breakthrough Designation in China for 2nd-line gastric cancer.

Negative

• Progression-free survival primary endpoint was not statistically significant in the 2nd and later-line setting, despite a trend toward improved PFS, which may limit the strength of the efficacy profile to overall survival benefits.

Filing Explained

Although the filing calls this the first pivotal readout from AstraZeneca's wholly owned ADC portfolio, it also says AstraZeneca obtained a global exclusive licence from KYM Biosciences in March 2023, so the disclosed structure is an exclusive licence rather than outright ownership.

Key Figures

CLDN18.2 expression threshold: 25% of tumour cells Estimated CLDN18.2-positive gastric/GEJ share: 60% of gastric/GEJ cancers Annual 2nd+ line CLDN18.2-positive gastric/GEJ patients: 183,500 patients +4 more

7 metrics

CLDN18.2 expression threshold 25% of tumour cells Eligibility criterion for CLARITY-Gastric01 and definition of CLDN18.2-positive gastric/GEJ/EAC cancers

Estimated CLDN18.2-positive gastric/GEJ share 60% of gastric/GEJ cancers Cancers expressing CLDN18.2 in 25% or more of tumour cells

Annual 2nd+ line CLDN18.2-positive gastric/GEJ patients 183,500 patients Estimated yearly in the US, EU, China and Japan for advanced or metastatic non-HER2-positive gastric/GEJ cancers

One-year survival in advanced gastric/GEJ less than 20% Proportion of patients with advanced or metastatic gastric/GEJ cancers surviving more than one year

Median survival with 2nd+ line treatment 5-9 months Median survival for patients receiving 2nd and later-line systemic treatments for advanced gastric cancer

CLARITY-Gastric01 trial centres 175 centres Number of centres participating in the trial across 19 countries

Global GI cancer incidence approximately 5 million new cases New gastrointestinal cancer cases worldwide in 2024, with about 3.3 million deaths

Key Terms

antibody drug conjugate, overall survival, progression-free survival, Orphan Drug Designation, +2 more

6 terms

antibody drug conjugate medical

"Sone-Ve is the first CLDN18.2-targeted antibody drug conjugate to demonstrate an overall survival benefit"

An antibody drug conjugate is a targeted medical treatment that combines a special antibody with a powerful drug, allowing precise delivery of the medicine directly to cancer cells or other harmful cells in the body. For investors, it represents a sophisticated approach to therapy that could improve treatment effectiveness and reduce side effects, potentially leading to significant growth opportunities in the biotech and pharmaceutical sectors.

overall survival medical

"demonstrated a statistically significant and highly clinically meaningful improvement in overall survival"

Overall survival is the average or median length of time patients remain alive after starting a treatment or entering a clinical study, measured regardless of cause of death. Investors care because it is a clear, hard measure of a therapy’s real-world benefit — like timing how long a new battery actually runs — and strong improvements in overall survival can drive regulatory approval, market adoption and revenue potential.

progression-free survival medical

"dual primary endpoints of OS in 3rd and later-line treatment and progression-free survival in the overall trial population"

Progression-free survival is the length of time during and after a treatment that a patient's disease does not get worse, measured from the start of treatment until the disease shows measurable signs of progression or the patient dies. Investors care because longer progression-free survival in clinical trials often signals that a drug is effective, improving chances of regulatory approval, market adoption, and revenue potential—think of it as a stopwatch showing how long a therapy can keep the illness at bay.

Orphan Drug Designation regulatory

"Sone-Ve has received Orphan Drug Designation from the US Food and Drug Administration and the European Commission"

Orphan drug designation is a special status given to medicines developed to treat rare diseases affecting only a small number of people. This status often provides benefits like faster approval processes and financial incentives, making it more attractive for companies to develop these drugs. For investors, it signals potential for exclusive market rights and reduced competition, which can impact the drug’s profitability.

Breakthrough Designation regulatory

"It has also received Breakthrough Designation in China for the 2nd-line treatment of gastric cancer"

A breakthrough designation is a regulatory fast-track status granted to an experimental medical treatment that shows early signs of substantial improvement over existing options. For investors, it matters because it speeds up and intensifies scrutiny by regulators—like giving a promising drug a VIP lane—raising the chance of quicker approval and higher commercial value, though it does not guarantee final approval or market success.

CLDN18.2 medical

"CLDN18.2 has emerged as an important therapeutic target for these patients"

Cldn18.2 is a specific form of a protein that normally helps hold stomach cells together and, when present on the surface of cancer cells, acts as a visible marker for targeted treatments. Investors should care because drugs and tests that recognize cldn18.2 can selectively find and attack tumors—like a lock-and-key system—making it a focal point for developing therapies, clinical trials, and companion diagnostics that can drive revenue and valuation.

AI-generated analysis. How Rhea-AI works. Not financial advice.

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FAQ

What clinical result did AstraZeneca (AZN) report for Sone-Ve in gastric cancer?

AstraZeneca reported that sonesitatug vedotin (Sone-Ve) significantly improved overall survival versus investigator's choice in 2nd and later-line CLDN18.2-positive advanced gastric, gastroesophageal junction and oesophageal adenocarcinoma cancers in the Phase III CLARITY-Gastric01 trial.

What were the primary endpoints in AstraZeneca (AZN)'s CLARITY-Gastric01 trial?

CLARITY-Gastric01 had dual primary endpoints of overall survival in 3rd and later-line treatment and progression-free survival in the overall 2nd and later-line population. Overall survival in 3rd and later-line was met, while PFS showed a trend but was not statistically significant.

How large is the potential Sone-Ve patient population cited by AstraZeneca (AZN)?

AstraZeneca cited an estimated 183,500 patients annually in the US, EU, China and Japan treated in the 2nd and later-line setting for advanced or metastatic CLDN18.2-positive, non-HER2-positive gastric/GEJ cancers, with about 60% of gastric/GEJ cancers expressing CLDN18.2 at the ≥25% threshold.

What safety profile did Sone-Ve show in the Phase III data disclosed by AstraZeneca (AZN)?

Sone-Ve was reported as well tolerated, with a safety profile consistent with prior experience and no new safety signals identified in the CLARITY-Gastric01 trial, supporting its potential as an antibody drug conjugate therapy in this setting.

What regulatory designations has Sone-Ve received according to AstraZeneca (AZN)?

Sone-Ve has Orphan Drug Designation from the US Food and Drug Administration and the European Commission for gastric and GEJ cancers, and Breakthrough Designation in China for 2nd-line treatment of gastric cancer.

What outcomes for advanced gastric and GEJ cancers does AstraZeneca (AZN) highlight?

AstraZeneca notes that for advanced or metastatic gastric/GEJ cancers, less than 20% of patients survive more than one year, and median survival with 2nd and later-line systemic treatments is only 5-9 months, underscoring the high unmet need.

FORM 6-K

SECURITIES AND EXCHANGE COMMISSION

Washington, D.C. 20549

Report of Foreign Issuer

Pursuant to Rule 13a-16 or 15d-16 of

the Securities Exchange Act of 1934

For the month of July 2026 

Commission File Number: 001-11960

AstraZeneca PLC

1 Francis Crick Avenue

Cambridge Biomedical Campus

Cambridge CB2 0AA

United Kingdom

Indicate by check mark whether the registrant files or will file annual reports under cover of Form 20-F or Form 40-F.

Form 20-F X Form 40-F __

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(1):

Indicate by check mark if the registrant is submitting the Form 6-K in paper as permitted by Regulation S-T Rule 101(b)(7): ______

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Yes __ No X

If “Yes” is marked, indicate below the file number assigned to the Registrant in connection with Rule 12g3-2(b): 82-_____________

AstraZeneca PLC

INDEX TO EXHIBITS

1.

Sone-Ve improved survival in gastric cancers

27 July 2026

Sonesitatug vedotin demonstrated a statistically significant and highly clinically meaningful improvement in overall survival in 2nd and later-line CLDN18.2-positive advanced gastric/GEJ cancers

Results provide opportunity to expand CLDN18.2 positivity to ≥25% expression, representing approximately 60% of patients in this setting

CLARITY-Gastric01 is the first Phase III trial to show overall survival benefit with an anti-CLDN18.2 ADC in this setting

First pivotal readout from AstraZeneca's wholly owned ADC portfolio

Positive high-level results from the CLARITY-Gastric01 global Phase III trial showed that sonesitatug vedotin (Sone-Ve) demonstrated a statistically significant and highly clinically meaningful improvement in overall survival (OS) in 2nd and later-line Claudin 18.2-positive advanced gastric cancers versus investigator's choice of therapy. The trial included patients with locally advanced or metastatic gastric cancer, gastroesophageal junction (GEJ) cancer, or oesophageal adenocarcinoma (EAC) with Claudin 18.2 (CLDN18.2) expression on at least 25% of tumour cells at any staining intensity.

The trial had dual primary endpoints of OS in 3rd and later-line treatment and progression-free survival (PFS) in the overall trial population. The trial met the dual primary endpoint of OS in 3rd and later-line treatment, and a key secondary endpoint of OS in the overall trial population of patients treated in the 2nd and later-line setting, demonstrating a statistically significant and highly clinically meaningful improvement.

For the other dual primary endpoint of PFS as assessed by blinded independent central review (BICR), results showed a trend toward improved PFS in patients treated in the 2nd and later-line setting but did not reach statistical significance.

The majority of patients with gastric/GEJ cancers are diagnosed at an advanced or metastatic stage, where the prognosis is especially poor and treatment options are limited, with less than 20% surviving more than one year.1,2 CLDN18.2 has emerged as an important therapeutic target for these patients, with an estimated 60% of gastric/GEJ cancers expressing CLDN18.2 in 25% or more of tumour cells.3 Each year, there are roughly 183,500 patients in the US, EU, China and Japan treated in the 2nd and later-line setting for advanced or metastatic CLDN18.2-positive, non-HER2-positive gastric/GEJ cancers.4

Rui-Hua Xu, M.D., Ph.D., Professor in the Department of Medical Oncology, Sun Yat-Sen University Cancer Center, Guangzhou, China, and principal investigator of the trial said: "Metastatic gastric cancer is an aggressive disease with very limited options once patients progress after first-line treatment. Sone-Ve is the first CLDN18.2-targeted antibody drug conjugate to demonstrate an overall survival benefit in this setting and has the potential to establish a new precision treatment for a broader population of patients with CLDN18.2 expression."

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, said: "Sone-Ve has the potential to reshape the treatment of gastric cancer by replacing classic chemotherapy with this novel targeted antibody drug conjugate to improve outcomes for patients. These transformative results from the first Phase III readout for Sone-Ve, together with our broad development programme, highlight the potential for Sone-Ve to become an important new medicine in CLDN18.2-positive cancers."

Sone-Ve was well tolerated, and its profile was consistent with the known safety profile of Sone-Ve with no new safety signals identified.

Sone-Ve is a potential global first-in-class CLDN18.2-targeting antibody drug conjugate (ADC) with a monomethyl auristatin E (MMAE) payload.

These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

Sone-Ve has received Orphan Drug Designation from the US Food and Drug Administration and the European Commission for the treatment of gastric and GEJ cancers. It has also received Breakthrough Designation in China for the 2nd-line treatment of gastric cancer.

Notes

Gastric and GEJ cancers

Gastric (stomach) cancer is the fifth most common cancer worldwide and the fifth-leading cause of cancer-related death.5 Nearly one million new patients were diagnosed with gastric cancer in 2024, with approximately 650,000 deaths reported globally. In many regions, its incidence has been increasing in patients younger than 50 years old, along with other gastrointestinal (GI) malignancies.5

GEJ cancer is a type of gastric cancer that arises from and spans the area where the oesophagus connects to the stomach.6

Most advanced gastric cancer patients will eventually experience disease progression after standard 1st-line therapies, and subsequent lines yield poor outcomes, with median survival of 5-9 months for patients receiving 2nd and later-line systemic treatments.7-9

CLARITY-Gastric01

CLARITY-Gastric01 is a randomised, open-label, sponsor-blinded, multicentre, global Phase III trial evaluating Sone-Ve as a 2nd and later-line therapy for patients with advanced or metastatic gastric cancer, GEJ cancer, or EAC with CLDN18.2 expression in 25% or more of tumour cells, with IHC+ of any intensity. In the trial, patients were randomised 1:1:1 in Stage 1 (dose selection) to Sone-Ve monotherapy 2.2 mg/kg or 1.8 mg/kg every three weeks, or investigator's choice of therapy, the comparator arm. In Stage 2, the trial continued with Sone-Ve 2.2 mg/kg as the recommended Phase III dose.

The efficacy analyses from this study will also provide the basis to evaluate the clinical performance of the Ventana SP455 assay for the identification of patients with advanced or metastatic gastric, GEJ or EAC cancers expressing CLDN18.2 who may benefit from Sone-Ve.

The trial is being conducted in 175 centres across 19 countries, including in North America, Europe, South America and Asia. Its dual primary endpoints are PFS as assessed by BICR in the 2nd and later-line setting and OS in the 3rd and later-line setting. A key secondary endpoint is OS in the 2nd and later-line setting.

Sonesitatug Vedotin (Sone-Ve)

Sone-Ve is a novel ADC targeting CLDN18.2, a protein found in the stomach lining and a validated therapeutic target in oncology, particularly for GI cancers. Sone-Ve consists of an anti-CLDN18.2 monoclonal antibody, a protease-degradable linker and a cytotoxic small molecule MMAE payload.

AstraZeneca entered into a global exclusive licence agreement with KYM Biosciences to develop and commercialise Sone-Ve in March 2023.

In addition to CLARITY-Gastric01, Sone-Ve is being evaluated in the CLARITY-Gastric02 Phase III trial in combination with capecitabine, with or without rilvegostomig, as a 1st-line treatment for advanced or metastatic gastric cancer, GEJ cancer and EAC. In Phase II development, Sone-Ve is being evaluated in patients with advanced solid tumours in multiple combinations across settings, including in CLDN18.2-positive pancreatic and biliary tract cancers (BTC).

AstraZeneca in GI cancers

AstraZeneca has a broad development programme for the treatment of GI cancers across several medicines and a variety of tumour types and stages of disease. In 2024, GI cancers collectively represented approximately 5 million new cancer cases leading to approximately 3.3 million deaths.10

Within this programme, the Company is committed to improving outcomes in gastric, liver, biliary tract, oesophageal, pancreatic and colorectal cancers.

Imfinzi (durvalumab), an anti-PDL1 antibody, is approved in the US, China, EU, Japan and other countries in combination with chemotherapy in locally advanced or metastatic BTC, in combination with Imjudo (tremelimumab) in unresectable hepatocellular carcinoma (HCC) and in combination with FLOT chemotherapy (fluorouracil, leucovorin, oxaliplatin, and docetaxel) in early-stage and locally advanced gastric and GEJ cancers. Imfinzi is also approved as a monotherapy in unresectable HCC in Japan, China and the EU.

Enhertu (trastuzumab deruxtecan), a HER2-directed ADC is approved in the US, China, EU, Japan and several other countries for HER2-positive advanced gastric cancer. Enhertu is jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Lynparza (olaparib), a first-in-class PARP inhibitor, is approved in the US and several other countries for the treatment of BRCA-mutated metastatic pancreatic cancer. Lynparza is developed and commercialised in collaboration with MSD (Merck & Co., Inc. inside the US and Canada).

Orpathys (savolitinib), an oral, potent, and highly selective MET tyrosine kinase inhibitor (TKI), has received conditional approval in China for the treatment of patients with locally advanced or metastatic gastric cancer or GEJ adenocarcinoma harbouring MET amplification who have progressed on at least two prior lines of systemic therapy. Orpathys is being jointly developed and commercialised by AstraZeneca and HUTCHMED.

The Company is also assessing rilvegostomig, a PD-1/TIGIT bispecific antibody, in combination with chemotherapy as an adjuvant therapy in BTC, and in combination with Enhertu in previously untreated, HER2-expressing, locally advanced or metastatic BTC. Rilvegostomig is also being evaluated in combination with bevacizumab with or without Imjudo as a 1st-line treatment in patients with advanced HCC, and as a 1st-line combination treatment in patients with HER2-positive, or CLDN18.2-positive and HER2-negative, locally advanced unresectable or metastatic gastric and GEJ cancers.

In addition to Sone-Ve, AstraZeneca is also advancing AZD5863, a novel CLDN18.2/CD3 T-cell engager bispecific antibody licensed from Harbour Biomed in Phase I development.

In early development, AstraZeneca is developing AZD7003, a Glypican 3 armoured CAR T, in HCC. The Company is also advancing a pan-KRAS inhibitor programme licensed from Jacobio Pharma, which is being evaluated in Phase I trials in advanced solid tumours with KRAS alterations, including in pancreatic ductal adenocarcinoma.

AstraZeneca in oncology

AstraZeneca is leading a revolution in oncology with the ambition to provide cures for cancer in every form, following the science to understand cancer and all its complexities to discover, develop and deliver life-changing medicines to patients.

The Company's focus is on some of the most challenging cancers. It is through persistent innovation that AstraZeneca has built one of the most diverse portfolios and pipelines in the industry, with the potential to catalyse changes in the practice of medicine and transform the patient experience.

AstraZeneca has the vision to redefine cancer care and, one day, eliminate cancer as a cause of death.

AstraZeneca

AstraZeneca (LSE/STO/NYSE: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Disease, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca's innovative medicines are sold in more than 125 countries and used by millions of patients worldwide. Please visit astrazeneca.com and follow the Company on Social Media @AstraZeneca.

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References 

1.   Davis JA, et al. Treatment heterogeneity and overall survival in patients with advanced/metastatic gastric or gastroesophageal junction adenocarcinoma in the United States. J Gastrointest Oncol. 2022 Jun;13(3):949-957.  

2.   Cancer Research UK. Survival for stomach cancer. https://www.cancerresearchuk.org/about-cancer/stomach-cancer/survival. Accessed July 2026.  

3.   Poniewierska-Baran A, et al. Claudin18.2 as a Promising Therapeutic Target in Gastric Cancer. Cells. 2025;14(16):1285.  

4.   AstraZeneca PLC. Investor Relations Epidemiology Spreadsheet. Top 8 Countries. Available at: https://www.astrazeneca.com/investor-relations.html. Accessed July 2026. 

5.   World Health Organization. International Agency for Research on Cancer. Stomach Fact Sheet. Available at: https://gco.iarc.who.int/today/en/fact-sheets-cancers/7/stomach. Accessed July 2026.  

6.   National Cancer Institute. Gastroesophageal junction. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/gastroesophageal-junction. Accessed July 2026. 

7.   Abderhalden LA, et al. Clinical Outcomes for Previously Treated Patients with Advanced Gastric or Gastroesophageal Junction Cancer: A Systematic Literature Review and Meta-Analysis. J Gastrointest Cancer. 2023;54(4):1031-1045. 

8.   Ford HE, et al. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. ⁠The Lancet Oncology, 2014;15(1), 78-86.

9.   Wilke H, et al. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a randomised, multicentre, double-blind, phase 3 trial. ⁠The Lancet Oncology, 2014;15(11), 1224-1235.

10.  World Health Organization. World Cancer Fact Sheet. Available at https://gco.iarc.who.int/today/en/fact-sheets-populations/900/world. Accessed July 2026. 

Matthew Bowden

Company Secretary

AstraZeneca PLC

SIGNATURES

Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned, thereunto duly authorized.

AstraZeneca PLC

Date: 27 July 2026

By: /s/ Matthew Bowden

Name: Matthew Bowden

Title: Company Secretary