‹‹‹First and solely EGFR inhibitor and focused remedy to point out profit in Stage III setting, extending progression-free survival by greater than three years

WILMINGTON, Del.–(BUSINESS WIRE)–Optimistic outcomes from the LAURA Part III trial confirmed AstraZeneca (NASDAQ:)’s TAGRISSO ® (osimertinib) demonstrated a statistically vital and extremely clinically significant enchancment in progression-free survival (PFS) for sufferers with unresectable, Stage III epidermal progress issue receptor-mutated (EGFRm) non-small cell lung most cancers (NSCLC) whose tumors have exon 19 deletions or exon 21 (L858R) mutations, after chemoradiotherapy (CRT) in comparison with placebo after CRT.

These outcomes will likely be offered at the moment throughout the Plenary Session on the 2024 American Society of Scientific Oncology (ASCO) Annual Assembly (summary #LBA4) and concurrently revealed in The New England Journal of Medication.

Outcomes confirmed TAGRISSO decreased the danger of illness development or demise by 84% in comparison with placebo (hazard ratio [HR] 0.16; 95% confidence interval [CI] 0.10-0.24; p

General survival (OS) information confirmed a positive development for TAGRISSO, though information weren’t mature on the time of this analysis. The trial will proceed to evaluate OS as a secondary endpoint.

Suresh Ramalingam, MD, Govt Director of Winship Most cancers Institute of Emory College, Atlanta, US and principal investigator within the trial, stated: The spectacular progression-free survival outcomes from the LAURA Part III trial characterize a significant breakthrough for sufferers with Stage III EGFR-mutated lung most cancers for whom no focused therapies can be found. Osimertinib delayed the danger of illness development or demise by an unprecedented 84% and may grow to be the brand new normal of take care of sufferers on this setting based mostly on these information.

Susan Galbraith, Govt Vice President, Oncology R&D, AstraZeneca, stated: TAGRISSO prolonged progression-free survival by greater than three years on this doubtlessly healing setting, reinforcing the necessity to take a look at and diagnose sufferers early. These practice-changing information cement the highly effective impression TAGRISSO could make as spine remedy in EGFR-mutated lung most cancers, particularly within the lives of those sufferers who’ve traditionally skilled early development following chemoradiotherapy.

‹Abstract of outcomes: LAURA

Security outcomes and discontinuation charges attributable to hostile occasions (AEs) have been as anticipated and no new security issues have been recognized. Grade 3 or greater AEs from all causes occurred in 35% of sufferers within the TAGRISSO arm versus 12% within the placebo arm.

TAGRISSO is accepted as monotherapy in additional than 100 international locations together with within the US, EU, China and Japan. Authorised indications embody for 1st-line remedy of sufferers with regionally superior or metastatic EGFRm NSCLC, regionally superior or metastatic EGFR T790M mutation-positive NSCLC, and adjuvant remedy of early-stage EGFRm NSCLC. TAGRISSO with the addition of chemotherapy can be accepted within the US and several other different international locations for 1st-line remedy of sufferers with regionally superior or metastatic EGFRm NSCLC.

IMPORTANT SAFETY INFORMATION

• There aren’t any contraindications for TAGRISSO
• Interstitial lung illness (ILD)/pneumonitis occurred in 4% of the 1813 TAGRISSO-treated sufferers; 0.4% of instances have been deadly. Within the FLAURA2 examine, ILD/pneumonitis occurred in 3.3% of the 276 sufferers who acquired TAGRISSO together with pemetrexed and platinum-based chemotherapy; 0.4% of instances have been deadly. Withhold TAGRISSO and promptly examine for ILD in sufferers who current with worsening of respiratory signs which can be indicative of ILD (eg, dyspnea, cough and fever). Completely discontinue TAGRISSO if ILD/pneumonitis is confirmed
• Coronary heart rate-corrected QT (QTc) interval prolongation happens in TAGRISSO-treated sufferers. Of the 1813 TAGRISSO monotherapy-treated sufferers in scientific trials, 1.1% have been discovered to have a QTc >500 msec, and 4.3% of sufferers had a rise from baseline QTc >60 msec. Of the 276 sufferers handled with TAGRISSO together with pemetrexed and platinum-based chemotherapy within the FLAURA2 examine, 1.8% have been discovered to have a QTc >500 msec, and 10.5% of sufferers had a rise from baseline QTc >60 msec. No QTc-related arrhythmias have been reported. Conduct periodic monitoring with ECGs and electrolytes in sufferers with congenital lengthy QTc syndrome, congestive coronary heart failure, electrolyte abnormalities, or those that are taking medicines identified to lengthen the QTc interval. Completely discontinue TAGRISSO in sufferers who develop QTc interval prolongation with indicators/signs of life-threatening arrhythmia
• Cardiomyopathy occurred in 3.8% of the 1813 TAGRISSO-treated sufferers; 0.1% of cardiomyopathy instances have been deadly. Within the FLAURA2 examine, cardiomyopathy occurred in 9% of the 276 sufferers who acquired TAGRISSO together with pemetrexed and platinum-based chemotherapy; 1.1% of cardiomyopathy instances have been deadly. A decline in left ventricular ejection fraction (LVEF) ‰¥10% from baseline and to
• Keratitis was reported in 0.6% of 1813 sufferers handled with TAGRISSO monotherapy in scientific trials. Promptly refer sufferers with indicators and signs suggestive of keratitis (comparable to eye irritation, lacrimation, gentle sensitivity, blurred imaginative and prescient, eye ache and/or crimson eye) to an ophthalmologist
• Postmarketing instances in step with erythema multiforme main (EMM), Stevens-Johnson syndrome (SJS) and poisonous epidermal necrolysis (TEN) have been reported in sufferers receiving TAGRISSO. Withhold TAGRISSO if EMM, SJS, or TEN is suspected and completely discontinue if confirmed
• Postmarketing instances of cutaneous vasculitis together with leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in sufferers receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, consider for systemic involvement, and think about dermatology session. If no different etiology could be recognized, think about everlasting discontinuation of TAGRISSO based mostly on severity
• Aplastic anemia has been reported in sufferers handled with TAGRISSO in scientific trials (0.06% of 1813) and postmarketing. Some instances had a deadly end result. Inform sufferers of the indicators and signs of aplastic anemia together with however not restricted to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and acquire a hematology session. If aplastic anemia is confirmed, completely discontinue TAGRISSO. Carry out full blood rely with differential earlier than beginning TAGRISSO, periodically all through remedy, and extra continuously if indicated
• Confirm being pregnant standing of females of reproductive potential previous to initiating TAGRISSO. Advise pregnant ladies of the potential threat to a fetus. Advise females of reproductive potential to make use of efficient contraception throughout remedy with TAGRISSO and for six weeks after the ultimate dose. Advise males with feminine companions of reproductive potential to make use of efficient contraception for 4 months after the ultimate dose
• Due to the potential for critical hostile reactions in breastfed infants from TAGRISSO, ladies mustn’t breastfeed throughout remedy with TAGRISSO and for two weeks after the ultimate dose
• Commonest ( ‰¥20%) hostile reactions, together with laboratory abnormalities, have been:
  • TAGRISSO monotherapy: leukopenia, lymphopenia, thrombocytopenia, anemia, diarrhea, rash, musculoskeletal ache, neutropenia, nail toxicity, dry pores and skin, stomatitis, and fatigue
  • TAGRISSO together with pemetrexed and platinum-based chemotherapy: leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry pores and skin, and elevated blood creatinine

INDICATIONS

• TAGRISSO is indicated as adjuvant remedy after tumor resection in grownup sufferers with non-small cell lung most cancers (NSCLC) whose tumors have epidermal progress issue receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved take a look at
• TAGRISSO is indicated for the first-line remedy of grownup sufferers with metastatic non-small cell lung most cancers (NSCLC) whose tumors have epidermal progress issue receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved take a look at
• TAGRISSO is indicated together with pemetrexed and platinum-based chemotherapy, for the first-line remedy of grownup sufferers with regionally superior or metastatic NSCLC whose tumors have epidermal progress issue receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved take a look at
• TAGRISSO is indicated for the remedy of grownup sufferers with metastatic epidermal progress issue receptor (EGFR) T790M mutation-positive NSCLC, as detected by an FDA-approved take a look at, whose illness has progressed on or after EGFR tyrosine kinase inhibitor (TKI) remedy

Please see full Prescription Info, together with Affected person Info for TAGRISSO.

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Notes

Lung most cancers

Lung most cancers is the main explanation for most cancers demise amongst each women and men, accounting for about one-fifth of all most cancers deaths.1 Lung most cancers is broadly break up into NSCLC and small cell lung most cancers.2 Annually there are an estimated 2.4 million individuals identified with lung most cancers globally, with 80-85% of sufferers identified with NSCLC, the most typical type of lung most cancers. The vast majority of all NSCLC sufferers are identified with superior illness.1-4

Roughly 10-15% of NSCLC sufferers within the US and Europe, and 30-40% of sufferers in Asia have EGFRm NSCLC.5-7 Sufferers with EGFRm NSCLC are significantly delicate to remedy with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signaling pathways that drive the expansion of tumor cells.8

LAURA

LAURA is a randomized, double-blind, placebo-controlled, multi-center, international Part III trial in sufferers with unresectable, Stage III EGFRm NSCLC whose illness has not progressed following definitive platinum‘based mostly CRT. Sufferers have been handled with TAGRISSO 80mg as soon as each day oral tablets till illness development, unacceptable toxicity or different discontinuation standards have been met. Upon development, sufferers within the placebo arm have been permitted to be handled with TAGRISSO.

The trial enrolled 216 sufferers in additional than 145 facilities throughout greater than 15 international locations, together with within the US, Europe, South America and Asia. That is the analysis of the first endpoint of PFS. The trial is ongoing and can proceed to evaluate the secondary endpoint of OS.

TAGRISSO

TAGRISSO ® (osimertinib) is a third-generation, irreversible EGFR-TKI with confirmed scientific exercise in NSCLC, together with in opposition to central nervous system (CNS) metastases. TAGRISSO (40 mg and 80 mg once-daily oral tablets) has been used to deal with practically 800,000 sufferers throughout its indications worldwide and AstraZeneca continues to discover TAGRISSO as a remedy for sufferers throughout a number of phases of EGFRm NSCLC.

There may be an in depth physique of proof supporting the usage of TAGRISSO in EGFRm NSCLC. TAGRISSO is the one focused remedy to enhance affected person outcomes in early-stage illness within the ADAURA Part III trial, regionally superior phases within the LAURA Part III trial and late-stage illness within the FLAURA Part III trial and FLAURA2 Part III trial.

As a part of AstraZeneca’s ongoing dedication to treating sufferers as early as potential in lung most cancers, TAGRISSO can be being investigated within the neoadjuvant setting within the NeoADAURA Part III trial with outcomes anticipated later this yr and within the early-stage adjuvant resectable setting within the ADAURA2 Part III trial.

The Firm can be researching methods to deal with tumor mechanisms of resistance via the SAVANNAH and ORCHARD Part II trials, and the SAFFRON Part III trial, which take a look at TAGRISSO plus savolitinib, an oral, potent and extremely selective MET TKI, in addition to different potential new medicines.

AstraZeneca in lung most cancers

AstraZeneca is working to convey sufferers with lung most cancers nearer to remedy via the detection and remedy of early-stage illness, whereas additionally pushing the boundaries of science to enhance outcomes within the resistant and superior settings. By defining new therapeutic targets and investigating progressive approaches, the Firm goals to match medicines to the sufferers who can profit most.

The Firm’s complete portfolio consists of main lung most cancers medicines and the following wave of improvements, together with TAGRISSO and gefitinib; durvalumab and tremelimumab-actl; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; in addition to a pipeline of potential new medicines and combos throughout numerous mechanisms of motion.

AstraZeneca is a founding member of the Lung Ambition Alliance, a worldwide coalition working to speed up innovation and ship significant enhancements for individuals with lung most cancers, together with and past remedy.

AstraZeneca in oncology

AstraZeneca is main a revolution in oncology with the ambition to supply cures for most cancers in each kind, following the science to grasp most cancers and all its complexities to find, develop and ship life-changing medicines to sufferers.

The Firm’s focus is on a few of the most difficult cancers. It’s via persistent innovation that AstraZeneca has constructed probably the most numerous portfolios and pipelines within the business, with the potential to catalyze modifications within the apply of drugs and rework the affected person expertise.

AstraZeneca has the imaginative and prescient to redefine most cancers care and, sooner or later, get rid of most cancers as a explanation for demise.

About AstraZeneca

AstraZeneca is a worldwide, science-led biopharmaceutical firm that focuses on the invention, improvement and commercialization of prescription medicines in Oncology, Uncommon Illnesses and BioPharmaceuticals, together with Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Primarily based in Cambridge, UK, AstraZeneca operates in over 100 international locations and its progressive medicines are utilized by tens of millions of sufferers worldwide. Please go to www.astrazeneca-us.com and observe us on social media @AstraZeneca.

References

1. World Well being Group. Worldwide Company for Analysis on Most cancers. Lung Reality Sheet. Obtainable at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed Could 2024. ‹
2. LUNGevity Basis. Forms of Lung Most cancers. Obtainable at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed Could 2024. ‹‹
3. Cheema PK, et al. Views on remedy advances for stage III regionally superior unresectable non-small-cell lung most cancers. Curr Oncol. 2019;26(1):37-42.
4. Cagle P, et al. Lung Most cancers Biomarkers: Current Standing and Future Developments. Archives Pathology Lab Med. 2013;137:1191-1198.‹‹
5. Keedy VL, et al. American Society of Scientific Oncology Provisional Scientific Opinion: Epidermal Development Issue Receptor (EGFR) Mutation Testing for Sufferers with Superior Non-Small-Cell Lung Most cancers Contemplating First-Line EGFR Tyrosine Kinase Inhibitor Remedy. J Clin Oncol. 2011;29:2121-27.‹
6. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Most cancers: a Polish, Single Establishment Examine and Systematic Evaluation of European Incidence. Int J Clin Exp Pathol. 2013;6:2800-12. ‹
7. Ellison G, et al. EGFR Mutation Testing in Lung Most cancers: a Evaluation of Obtainable Strategies and Their Use for Evaluation of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013;66:79-89.
8. Cross DA, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Most cancers. Most cancers Discov. 2014;4(9):1046-1061.‹

US-90204 Final Up to date 06/24

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