Based on LAURA Phase III trial results which showed TAGRISSO extended median progression-free survival by more than three years

AstraZeneca’s TAGRISSO^® (osimertinib)​ has been approved in the US for the treatment of adult patients with unresectable, Stage III epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC) whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy (CRT). TAGRISSO is indicated for patients with exon 19 deletions or exon 21 (L858R) mutations, as detected by a FDA-approved test.

The approval follows a Priority Review by the Food and Drug Administration (FDA) that was based on results from the LAURA Phase III trial, which were presented during the Plenary Session at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and simultaneously published in The New England Journal of Medicine.

TAGRISSO reduced the risk of disease progression or death by 84% compared to placebo (hazard ratio 0.16; 95% confidence interval 0.10-0.24; p<0.001) as assessed by blinded independent central review. Median progression-free survival (PFS) was 39.1 months in patients treated with TAGRISSO versus 5.6 months for placebo.

Overall survival (OS) results remain immature at this current analysis. The trial continues to assess OS as a secondary endpoint.

Each year in the US, there are more than 200,000 people diagnosed with lung cancer, and 80-85% of these patients are diagnosed with NSCLC, the most common form of lung cancer.^1-3 Approximately 15% of NSCLC patients in the US have EGFR mutations.⁴ Nearly one in five people diagnosed with NSCLC has an unresectable tumor.⁵

Suresh Ramalingam, MD, Executive Director of Winship Cancer Institute of Emory University, Atlanta, US, and principal investigator in the trial, said: “This approval represents a major breakthrough for patients with Stage III, EGFR-mutated lung cancer who will now have the opportunity to benefit from osimertinib. Patients treated with osimertinib lived without disease progression by more than three years in the LAURA trial, and this impressive benefit underscores the importance of diagnosing and testing lung cancer patients as early as possible.”

Dave Fredrickson, Executive Vice President, Oncology Business Unit, AstraZeneca, said: “The approval of TAGRISSO for patients with Stage III, unresectable EGFR-mutated non-small cell lung cancer addresses a critical need for patients with these mutations who have never had the option of targeted therapy before. The results of the LAURA trial show the powerful impact TAGRISSO can make as backbone therapy in this disease, and with this approval, patients across all stages of EGFR-mutated non-small cell lung cancer can now benefit.”

The safety and tolerability of TAGRISSO in the LAURA trial was consistent with its established profile and no new safety concerns were identified.

TAGRISSO is approved for patients with EGFR mutations in the 1st-line metastatic setting as a monotherapy and in combination with chemotherapy, and as an adjuvant treatment for early-stage disease. TAGRISSO is currently under review with regulatory authorities in other countries around the world for this indication.

IMPORTANT SAFETY INFORMATION

• There are no contraindications for TAGRISSO

• TAGRISSO can cause severe and fatal interstitial lung disease (ILD)/pneumonitis. ILD/pneumonitis occurred in 4% of the 1813 patients treated with TAGRISSO monotherapy who had not received recent definitive chemoradiation therapy; 0.4% of cases were fatal ILD/Pneumonitis with TAGRISSO in combination with Pemetrexed and Platinum-based Chemotherapy:
  • In the FLAURA2 study, ILD/pneumonitis occurred in 3.3% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 0.4% of cases were fatal

ILD/Pneumonitis Following Definitive Platinum-based Chemoradiation Therapy (CRT):

• In the LAURA study, following definitive platinum-based CRT, ILD/pneumonitis including radiation pneumonitis, occurred in 80 of the 143 patients (56%) who received TAGRISSO monotherapy and 28 of the 73 patients (38%) who received placebo. There was one fatal case (0.7%), 3.5% Grade 3, 34% Grade 2, and 18% Grade 1 adverse reactions of ILD/pneumonitis in TAGRISSO-treated patients. For TAGRISSO-treated patients, ILD/pneumonitis led to permanent discontinuation of TAGRISSO in 7% of patients and dosage interruptions of TAGRISSO in 35% of patients. Among the 46 patients who were rechallenged with TAGRISSO, 11% had recurrence of ILD/pneumonitis. In the 80 TAGRISSO-treated patients, ILD/pneumonitis resolved in 40%, resolved with sequelae in 1.3%, were resolving in 16%, did not resolve in 41%, and resulted in death in 1.3%

For patients receiving TAGRISSO who have not received recent definitive platinum-based CRT, withhold TAGRISSO and promptly investigate for ILD in patients who present with worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Permanently discontinue TAGRISSO if ILD/pneumonitis is confirmed. For patients who have received recent definitive platinum-based CRT with Grade 1 ILD/pneumonitis, continue TAGRISSO or interrupt and restart, as appropriate. Permanently discontinue TAGRISSO in patients diagnosed with Grade ≥2 ILD/pneumonitis

• TAGRISSO can cause heart rate-corrected QT (QTc) interval prolongation. Of the 1813 TAGRISSO monotherapy-treated patients in clinical trials, 1.1% were found to have a QTc >500 msec, and 4.3% of patients had an increase from baseline QTc >60 msec. Of the 276 patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy in the FLAURA2 study, 1.8% were found to have a QTc >500 msec, and 10.5% of patients had an increase from baseline QTc >60 msec. No QTc-related arrhythmias were reported. Clinical trials of TAGRISSO did not enroll patients with baseline QTc of >470 msec. Conduct periodic monitoring with ECGs and electrolytes in patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or those who are taking medications known to prolong the QTc interval. Permanently discontinue TAGRISSO in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia

• TAGRISSO can cause cardiomyopathy, including cardiac failure, chronic cardiac failure, congestive heart failure, pulmonary edema or decreased ejection fraction. Cardiomyopathy occurred in 3.8% of the 1813 TAGRISSO-treated patients; 0.1% of cardiomyopathy cases were fatal. In the FLAURA2 study, cardiomyopathy occurred in 9% of the 276 patients who received TAGRISSO in combination with pemetrexed and platinum-based chemotherapy; 1.1% of cardiomyopathy cases were fatal. A decline in left ventricular ejection fraction (LVEF) ≥10% from baseline and to <50% LVEF occurred in 4.2% of 1557 patients who had baseline and at least one follow-up LVEF assessment. In the ADAURA study, 1.5% (5/325) of TAGRISSO-treated patients experienced LVEF decreases ≥10% from baseline and a drop to <50%. In the LAURA study, following platinum-based CRT, 3% (4/135) of TAGRISSO-treated patients and no placebo-treated patients experienced LVEF decreases ≥10% and a drop to <50%. In the FLAURA2 study, 8% (21/262) of patients treated with TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, who had baseline and at least one follow-up LVEF assessment, experienced LVEF decreases ≥10% and a drop to <50%. For patients receiving TAGRISSO monotherapy, conduct cardiac monitoring in patients with cardiac risk factors, including assessment of LVEF at baseline and during treatment. For patients receiving TAGRISSO in combination with pemetrexed and platinum-based chemotherapy, conduct cardiac monitoring in all patients, including assessment of LVEF at baseline and during treatment. Assess LVEF in patients who develop relevant cardiac signs or symptoms during treatment. For symptomatic congestive heart failure, permanently discontinue TAGRISSO

• Keratitis was reported in 0.6% of 1813 patients treated with TAGRISSO monotherapy in clinical trials. Promptly refer patients with signs and symptoms suggestive of keratitis (such as eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) to an ophthalmologist

• Postmarketing cases consistent with erythema multiforme major (EMM), Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if EMM, SJS, or TEN is suspected and permanently discontinue if confirmed

• Postmarketing cases of cutaneous vasculitis including leukocytoclastic vasculitis, urticarial vasculitis, and IgA vasculitis have been reported in patients receiving TAGRISSO. Withhold TAGRISSO if cutaneous vasculitis is suspected, evaluate for systemic involvement, and consider dermatology consultation. If no other etiology can be identified, consider permanent discontinuation of TAGRISSO based on severity

• Aplastic anemia has been reported in TAGRISSO-treated patients in clinical trials (0.06% of 1813) and postmarketing. Some cases had a fatal outcome. Inform patients of the signs and symptoms of aplastic anemia including but not limited to, new or persistent fevers, bruising, bleeding, and pallor. If aplastic anemia is suspected, withhold TAGRISSO and obtain a hematology consultation. If aplastic anemia is confirmed, permanently discontinue TAGRISSO. Perform complete blood count with differential before starting TAGRISSO, periodically throughout treatment, and more frequently if indicated

• Verify pregnancy status of females of reproductive potential prior to initiating TAGRISSO. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TAGRISSO and for 6 weeks after the last dose. Advise males with female partners of reproductive potential to use effective contraception for 4 months after the last dose

• Because of the potential for serious adverse reactions in breastfed infants from TAGRISSO, women should not breastfeed during treatment with TAGRISSO and for 2 weeks after the last dose

• Most common (≥20%) adverse reactions, including laboratory abnormalities, were:
  • TAGRISSO monotherapy: leukopenia, lymphopenia, thrombocytopenia, anemia, diarrhea, rash, musculoskeletal pain, neutropenia, nail toxicity, dry skin, stomatitis, and fatigue
  • TAGRISSO monotherapy following platinum-based chemoradiation therapy: lymphopenia, leukopenia, ILD/pneumonitis, thrombocytopenia, neutropenia, rash, diarrhea, nail toxicity, musculoskeletal pain, cough and COVID-19
  • TAGRISSO in combination with pemetrexed and platinum-based chemotherapy: leukopenia, thrombocytopenia, neutropenia, lymphopenia, rash, diarrhea, stomatitis, nail toxicity, dry skin, and increased blood creatinine

INDICATIONS

• TAGRISSO is indicated as adjuvant therapy after tumor resection in adult patients with non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

• TAGRISSO is indicated for the treatment of adult patients with locally advanced, unresectable (stage III) NSCLC whose disease has not progressed during or following concurrent or sequential platinum-based chemoradiation therapy and whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

• TAGRISSO is indicated for the first-line treatment of adult patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

• TAGRISSO is indicated in combination with pemetrexed and platinum-based chemotherapy, for the first-line treatment of adult patients with locally advanced or metastatic NSCLC whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test

• TAGRISSO is indicated for the treatment of adult patients with metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive NSCLC, as detected by an FDA-approved test, whose disease has progressed on or after EGFR tyrosine kinase inhibitor (TKI) therapy

Please see complete Prescription Information, including Patient Information for TAGRISSO.

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Notes

Lung cancer

Each year, an estimated 2.4 million people are diagnosed with lung cancer globally.⁶ Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.⁶ Lung cancer is broadly split into NSCLC and small cell lung cancer.² The majority of all NSCLC patients are diagnosed with advanced disease.⁷

Approximately 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia have EGFRm NSCLC.^4,8-9 Patients with EGFRm NSCLC are particularly sensitive to treatment with an EGFR-tyrosine kinase inhibitor (EGFR-TKI) which blocks the cell-signaling pathways that drive the growth of tumor cells.¹⁰

LAURA

LAURA is a randomized, double-blind, placebo-controlled, multi-center, global Phase III trial in patients with unresectable, Stage III EGFRm NSCLC whose disease has not progressed following definitive platinum-based CRT. Patients were treated with TAGRISSO 80 mg once-daily oral tablets until disease progression, unacceptable toxicity or other discontinuation criteria were met. Upon progression, patients in the placebo arm were offered treatment with TAGRISSO.

The trial enrolled 216 patients in more than 145 centers across more than 15 countries, including in the US, Europe, South America and Asia. This is the analysis of the primary endpoint of PFS. The trial is ongoing and will continue to assess the secondary endpoint of OS.

TAGRISSO

TAGRISSO^® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. TAGRISSO (40 mg and 80 mg once-daily oral tablets) has been used to treat nearly 800,000 patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC.

There is an extensive body of evidence supporting the use of TAGRISSO as standard of care in EGFRm NSCLC. TAGRISSO improved patient outcomes in early-stage disease in the ADAURA Phase III trial, locally advanced disease in the LAURA Phase III trial, late-stage disease in the FLAURA Phase III trial, and with chemotherapy in the FLAURA2 Phase III trial.

As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, TAGRISSO is also being investigated in the neoadjuvant setting in the NeoADAURA Phase III trial with results expected later this year and in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

The Company is also researching ways to address tumor mechanisms of resistance through the SAVANNAH and ORCHARD Phase II trials, and the SAFFRON Phase III trial, which test TAGRISSO plus savolitinib, an oral, potent and highly selective MET TKI, as well as other potential new medicines.

AstraZeneca in lung cancer

AstraZeneca is working to bring patients with lung cancer closer to cure through the detection and treatment of early-stage disease, while also pushing the boundaries of science to improve outcomes in the resistant and advanced settings. By defining new therapeutic targets and investigating innovative approaches, the Company aims to match medicines to the patients who can benefit most.

The Company’s comprehensive portfolio includes leading lung cancer medicines and the next wave of innovations, including TAGRISSO and gefitinib; durvalumab and tremelimumab-aclt; fam-trastuzumab deruxtecan-nxki and datopotamab deruxtecan in collaboration with Daiichi Sankyo; savolitinib in collaboration with HUTCHMED; as well as a pipeline of potential new medicines and combinations across diverse mechanisms of action.

AstraZeneca is a founding member of the Lung Ambition Alliance, a global coalition working to accelerate innovation and deliver meaningful improvements for people with lung cancer, including and beyond treatment.

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 catalyze 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 is a global, science-led biopharmaceutical company that focuses on the discovery, development and commercialization of prescription medicines in Oncology, Rare Diseases and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Based in Cambridge, UK, AstraZeneca operates in over 125 countries, and its innovative medicines are used by millions of patients worldwide. For more information, please visit www.astrazeneca-us.com and follow us on social media @AstraZeneca.

References

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2. ​LUNGevity Foundation. Types of Lung Cancer. Available at: https://www.lungevity.org/lung-cancer-basics/types-of-lung-cancer. Accessed August 2024.
3. American Cancer Society. What Is Lung Cancer? Available at: https://www.cancer.org/cancer/types/lung-cancer/about/what-is.html. Accessed August 2024.
4. Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011;29(15):2121-2127.
5. ​Quint LE. Lung cancer: assessing resectability. Cancer Imaging. 2004;4(1):15-18.
6. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed August 2024.
7. ​Cagle P, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med. 2013;137(9):1191-1198.
8. Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013;6(12): 2800-2812.
9. Ellison G, et al. EGFR Mutation Testing in Lung Cancer: a Review of Available Methods and Their Use for Analysis of Tumour Tissue and Cytology Samples. J Clin Pathol. 2013;66(2):79-89.
10. ​Cross DAE, et al. AZD9291, an Irreversible EGFR TKI, Overcomes T790M-Mediated Resistance to EGFR Inhibitors in Lung Cancer. Cancer Discov. 2014;4(9):1046-1061.

US-93979 Last Updated 9/24

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