New study results reinforce TAGRISSO® (osimertinib) as the backbone therapy for EGFR-mutated lung cancer across stages and settings

In LAURA Phase III trial, TAGRISSO continues to demonstrate improved overall survival trend in unresectable, Stage III setting

SAVANNAH and ORCHARD Phase II trials show the addition of savolitinib or datopotamab deruxtecan-dlnk to TAGRISSO upon disease progression demonstrates strong clinical activity

WILMINGTON, Del.–(BUSINESS WIRE)–New study results presented at the European Lung Cancer Congress (ELCC) 2025, March 26 to 29, demonstrate the role of AstraZeneca’s TAGRISSO^® (osimertinib), as monotherapy and as the backbone for novel combinations, across stages and settings of epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). Highlights include:

• LAURA Phase III trial of TAGRISSO in unresectable, Stage III EGFRm NSCLC after chemoradiotherapy (CRT) (LBA4).
• SAVANNAH Phase II trial of TAGRISSO plus savolitinib in advanced EGFRm NSCLC with high levels of MET overexpression and/or amplification following disease progression on 1st-line TAGRISSO (#2O).
• ORCHARD Phase II platform trial of TAGRISSO plus datopotamab deruxtecan-dlnk in advanced EGFRm NSCLC following disease progression on 1st-line TAGRISSO (#1O).
• FLAURA2 Phase III trial of TAGRISSO plus chemotherapy as 1st-line treatment for advanced EGFRm NSCLC (#53P).

Myung-Ju Ahn, MD, PhD, Professor of Hemato-Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, said: “A critical goal in treating every patient with lung cancer is to not only extend a patient’s life but also maintain quality of life while on treatment. The continued overall survival trend seen here at ELCC in the unresectable Stage III setting and the promising data for combinations that can address progression in the advanced setting, together reinforce osimertinib as an effective, safe and convenient treatment for patients with EGFR-mutated lung cancer across stages and lines of treatment.”

Susan Galbraith, Executive Vice President, Oncology Hematology R&D, AstraZeneca, said: “Having now treated more than one million patients around the world, TAGRISSO has repeatedly transformed expectations for patients with EGFR-mutated lung cancer by not only extending survival but also showing it is possible to maintain quality of life during cancer treatment. The breadth of data at ELCC reinforce TAGRISSO as the backbone therapy for patients with this disease and show that adding savolitinib or datopotamab deruxtecan-dlnk at the time of disease progression can help prolong patients’ responses to treatment.”

Professor Virginia Harrison, EGFR Positive UK, said: “For people undergoing treatment for lung cancer, maintaining quality of life is so important, but it can be challenging. The development of simple and effective treatment regimens that minimize negative side effects can make a huge difference. We are excited to see this progress for patients with EGFR-mutated lung cancer, where there is still significant unmet need.”

TAGRISSO continued to demonstrate encouraging overall survival (OS) trend in unresectable, Stage III setting in LAURA trial

Updated results from the LAURA Phase III trial showed an improved trend towards OS benefit with TAGRISSO compared to placebo in patients with unresectable, Stage III EGFRm NSCLC (hazard ratio [HR] 0.67; 95% confidence interval [CI] 0.40, 1.14, maturity 31%). Median OS was 58.8 months (95% CI 54.1, not calculable [NC]) in patients treated with TAGRISSO versus 54.1 months with placebo (95% CI 42.1, NC), despite 78% of patients on placebo receiving subsequent treatment with TAGRISSO upon progression. The trial will continue to assess OS as a key secondary endpoint at the final analysis.

TAGRISSO previously demonstrated a statistically significant and highly clinically meaningful improvement in progression-free survival (PFS). These results were published in The New England Journal of Medicine and formed the basis for regulatory approvals around the world including in the US, EU and China.

Safety results and discontinuation rates due to adverse events (AEs) were as expected and no new safety concerns were identified.

TAGRISSO plus savolitinib showed durable response rates in lung cancer patients with high levels of MET overexpression and/or amplification whose disease progressed on 1st-line TAGRISSO in SAVANNAH trial

Results from the SAVANNAH Phase II trial showed TAGRISSO plus savolitinib (300 mg twice-daily [BID]) demonstrated a clinically meaningful and durable objective response rate (ORR) in patients with EGFRm NSCLC with high levels of MET overexpression and/or amplification whose disease progressed on treatment with 1st-line TAGRISSO. Among patients screened for enrollment in SAVANNAH, an estimated 62% had tumors with MET overexpression and/or amplification, and approximately 34% met the defined high MET level cut-off.

TAGRISSO plus savolitinib demonstrated a confirmed ORR of 56% (95% CI 45-67%), with a median duration of response (DoR) of 7.1 months (95% CI 5.6-9.6). Median PFS (mPFS) was 7.4 months (95% CI 5.5-7.6).

Safety results and discontinuation rates due to AEs were consistent with the established profiles of each medicine and no new safety concerns were reported. In all patients treated with TAGRISSO plus savolitinib (300 mg BID), Grade 3 or higher AEs occurred in 57% of patients.

Savolitinib is an oral, potent and highly selective MET tyrosine kinase inhibitor (TKI) being jointly developed and commercialized by AstraZeneca and HUTCHMED. In 2023, TAGRISSO plus savolitinib received Fast Track designation from the Food and Drug Administration (FDA) in this setting.

TAGRISSO plus datopotamab deruxtecan-dlnk showed encouraging response rates in patients whose disease progressed on 1st-line TAGRISSO in ORCHARD trial

First results from the TAGRISSO plus datopotamab deruxtecan-dlnk module of the ORCHARD Phase II platform trial showed the combination demonstrated promising efficacy and manageable safety in patients with advanced EGFRm NSCLC whose disease progressed on treatment with TAGRISSO.

The module enrolled an all-comer population of patients with EGFRm NSCLC and evaluated two doses of datopotamab deruxtecan-dlnk (4 or 6 mg/kg) which, in combination with TAGRISSO, showed similar ORRs of 43% (80% CI 31-55%) and 36% (80% CI 25-49%), respectively. PFS and DoR results favored the 6 mg/kg dose with a mPFS of 11.7 months (95% CI 8.3, NC) and 64% of patients continuing to respond at 9 months versus a mPFS of 9.5 months (95% CI 7.2-9.8) and 15% of patients continuing to respond at 9 months on the 4 mg/kg dose.

The safety profile of TAGRISSO plus datopotamab deruxtecan-dlnk was consistent with the known safety profiles of each medicine and no new safety concerns were identified at either dose level. Grade 3 or higher treatment-related AEs occurred in 34% and 56% of patients receiving the 4 mg/kg or 6 mg/kg doses, respectively.

Datopotamab deruxtecan-dlnk is a specifically engineered TROP2-directed antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialized by AstraZeneca and Daiichi Sankyo. The Companies are evaluating datopotamab deruxtecan-dlnk alone and with TAGRISSO as treatment for patients with advanced or metastatic EGFRm NSCLC in the TROPION-Lung14 and TROPION-Lung15 Phase III trials.

New results for TAGRISSO plus chemotherapy in the 1st-line setting reinforce strong PFS benefit in FLAURA2 Phase III trial

An exploratory post-hoc analysis of the FLAURA2 Phase III trial assessed PFS by length of exposure to pemetrexed maintenance treatment in patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with TAGRISSO with the addition of chemotherapy (pemetrexed plus cisplatin) followed by maintenance treatment with TAGRISSO and chemotherapy (pemetrexed) or TAGRISSO alone. Results showed an mPFS of more than two years regardless of length of pemetrexed maintenance exposure, with a trend associating longer PFS with longer pemetrexed treatment.

The safety profile of TAGRISSO plus chemotherapy was consistent with the established profiles of the individual medicines. Grade 3 or higher chemotherapy-related AEs were reported in 16% of patients who received maintenance treatment for 3 to less than 9 months, and 10% for patients who received maintenance for 9 or more months. Chemotherapy discontinuation rates due to AEs were 18% and 10%, respectively.

TAGRISSO plus chemotherapy previously demonstrated a statistically significant and clinically meaningful improvement in PFS. These results were published in The New England Journal of Medicine and formed the basis for regulatory approvals around the world including in the US, EU, Japan and China. Previously presented OS data from the second interim analysis showed a favorable trend with the TAGRISSO plus chemotherapy arm (HR 0.75; 95% CI 0.57-0.97, maturity 41%), with consistent results across all prespecified subgroups. The trial will continue to assess OS as a key secondary endpoint.

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

Notes

NSCLC

Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths.¹ Lung cancer is broadly split into small cell lung cancer or NSCLC, the latter accounting for about 80% of cases.² Approximately 10 to 15% of patients with NSCLC in the US and Europe and 30 to 40% of patients in Asia have an EGFR mutation.^3-5

While EGFR-TKIs have significantly improved outcomes in the 1st-line setting, mechanisms of resistance and disease progression are extremely common, and a significant unmet need exists in later-line settings for effective and well-tolerated treatment options.^6-9

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 (QD) 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.

SAVANNAH

SAVANNAH is an ongoing randomized, global Phase II trial studying the efficacy of savolitinib added to TAGRISSO in patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression and/or amplification whose disease progressed following treatment with TAGRISSO. Based on the original single-arm trial design, patients were treated with savolitinib 300 or 600 mg QD or 300 mg BID, in combination with oral TAGRISSO 80 mg QD. In 2022, a comparison of savolitinib 300 mg BID and TAGRISSO 80 mg QD to savolitinib 300 mg BID and placebo was added to the trial to evaluate contribution of components.

The trial has enrolled 369 patients to date in more than 80 centers globally, including in the US, Canada, Europe, South America and Asia. The primary endpoint is ORR and key secondary endpoints include PFS and DoR.

In August 2022, positive interim ORR results from the SAVANNAH trial were presented at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer (WCLC).

The global SAFFRON Phase III trial will further assess the TAGRISSO plus savolitinib combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following treatment with TAGRISSO. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH.

ORCHARD

ORCHARD (Osimertinib Resistance CoHorts, Addressing 1L Relapse Drivers) is an open-label, multi-center Phase II platform trial evaluating numerous TAGRISSO-based combinations as a treatment for patients with advanced EGFRm NSCLC whose disease has progressed on 1st-line TAGRISSO. The trial has 10 modules examining the efficacy, safety and tolerability of these targeted and non-targeted combination options, including TAGRISSO 80 mg QD plus datopotamab deruxtecan-dlnk given intravenously at 4 or 6 mg/kg on day one of every three-week cycle.

The trial has enrolled 247 patients to date in more than 40 centers globally, including in the US, Europe and Asia. The primary endpoint is ORR. Key secondary endpoints include PFS and DoR.

FLAURA2

FLAURA2 is a randomized, open-label, multi-center, global Phase III trial in the 1st-line treatment of patients with locally advanced (Stage IIIB-IIIC) or metastatic (Stage IV) EGFRm NSCLC. Patients were treated with TAGRISSO 80 mg QD oral tablets with the addition of chemotherapy (pemetrexed (500 mg/m2) plus cisplatin (75 mg/m2) or carboplatin (AUC5) every three weeks for four cycles, followed by TAGRISSO with pemetrexed maintenance every three weeks.

The trial enrolled 557 patients in more than 150 centers across more than 20 countries, including in the US, Europe, South America and Asia. The primary endpoint is 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 metastases. TAGRISSO (40 mg and 80 mg QD oral tablets) has been used to treat 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 in EGFRm NSCLC. TAGRISSO is the only targeted therapy to improve patient outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials, locally advanced stages in the LAURA Phase III trial and late-stage disease in the FLAURA and FLAURA2 Phase III trials.

As part of AstraZeneca’s ongoing commitment to treating patients as early as possible in lung cancer, TAGRISSO is also being investigated in the early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

Savolitinib

Savolitinib is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors.

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