RegulationFast Track (United States), Accelerated Approval (United States), Orphan Drug (United States), Priority Review (China), Breakthrough Therapy (China), Special Review Project (China), Priority Review (Australia), Accelerated assessment (European Union), Priority Review (United States), Breakthrough Therapy (United States)

Structure/Sequence

Molecular FormulaC29H37N7O5S

InChIKeyFUKSNUHSJBTCFJ-UHFFFAOYSA-N

CAS Registry1421373-66-1

373

Clinical Trials associated with Osimertinib mesylate

NCT06918782

/ Not yet recruitingPhase 2

Real-world Experience With Combination Chemotherapy and Osimertinib in Poor Prognostic Group of Metastatic EGFR-mutated Lung Adenocarcinoma

The aims of this study are to determine the potential clinical benefits (in terms of PFS, objective response and OS) of add-on systemic chemotherapy (pemetrexed+carboplatin/cisplatin) to first-line osimertinib treatment among the poor prognostic group of metastatic EGFR-mutant lung adenocarcinoma, i.e. failure of plasma ctDNA EGFR mutant clearance at week 3 after osimertinib treatment

Start Date01 May 2025

Sponsor / Collaborator

The University of Hong Kong

NCT06829459

/ RecruitingPhase 3

A Randomized, Controlled, Open-label Phase III Clinical Study to Evaluate the Efficacy and Safety of Glumetinib Combined With Osimertinib Mesylate Versus Platinum-based Doublet Chemotherapy in Non-Small Cell Lung Cancer Patients With MET Amplification and/or Overexpression After Resistance to EGFR-TKIs

The is a randomized, controlled, open-label Phase III clinical study to evaluate the efficacy and safety of glumetinib combined with osimertinib mesylate versus platinum-based doublet chemotherapy in non-small cell lung cancer( NSCLC) patients with MET amplification and/or overexpression after resistance to EGFR-TKIs..
Approximately 350 NSCLC patients with MET amplification and/or overexpression after previous treatment with EGFR-TKIs are planned to be enrolled. After patients sign the informed consent form (ICF), those who are eligible for enrollment after screening examinations will be randomized to the investigational group or the control group in a 1:1 ratio by the central randomization system (IWRS).

Start Date03 Apr 2025

Sponsor / Collaborator

Shanghai JMT Biological Technology Co Ltd

NCT06908772

/ Not yet recruitingPhase 2/3

A Multicenter Phase II/III Clinical Study on the Efficacy and Safety of Glumetinib Combined With Osimertinib as First-Line Treatment in Non-Small Cell Lung Cancer Patients With Classical EGFR Mutations Accompanied by MET Amplification or Overexpression

To evaluate the efficacy and safety of glumetinib combined with osimertinib as the first-line treatment for locally advanced or metastatic NSCLC.

Start Date01 Apr 2025

Sponsor / Collaborator

Shanghai JMT Biological Technology Co Ltd

100 Clinical Results associated with Osimertinib mesylate

100 Translational Medicine associated with Osimertinib mesylate

100 Patents (Medical) associated with Osimertinib mesylate

4,428

Literatures (Medical) associated with Osimertinib mesylate

01 Dec 2025·Current Neurology and Neuroscience Reports

Emerging Therapies for Brain Metastases in NSCLC, Breast Cancer, and Melanoma: A Critical Review

Review

Author: Gowda, Maya ; Camacho, Alejandra M ; Ranjan, Tulika ; Ahluwalia, Manmeet S ; Podder, Vivek

PURPOSE OF REVIEW:

Advancements in precision medicine have shifted the treatment paradigm of brain metastases (BM) from non-small cell lung cancer (NSCLC), breast cancer, and melanoma, especially through targeted therapies focused on specific molecular drivers. These novel agents have improved outcomes by overcoming challenges posed by the blood-brain barrier (BBB) and resistance mechanisms, enabling more effective treatment of BM.

RECENT FINDINGS:

In NSCLC, therapies such as osimertinib have improved efficacy in treating EGFR-mutant BM, with emerging combinations such as amivantamab and lazertinib offering promising alternatives for patients resistant to frontline therapies. In HER2-positive breast cancer, significant advancements with tucatinib and trastuzumab deruxtecan (T-DXd) have transformed the treatment landscape, achieving improved survival and intracranial control in patients with BM. Similarly, in triple-negative breast cancer (TNBC), novel therapies such as sacituzumab govitecan (SG) and datopotamab deruxtecan (Dato-DXd) offer new hope for managing BM. For melanoma, the combination of immune checkpoint inhibitors such as nivolumab and ipilimumab has proven effective in enhancing survival for patients with BM, both in BRAF-mutant and wild-type cases. Developing targeted therapies penetrating the BBB has revolutionized BM treatment by targeting key drivers like EGFR, ALK, HER2, and BRAF. Despite improved survival, challenges persist, particularly for patients with resistant genetic alterations. Future research should optimise combination therapies, overcome resistance, and refine treatment sequencing. Continued emphasis on personalized, biomarker-driven approaches offers the potential to further improve outcomes, even for complex cases.

01 Dec 2025·CANCER CHEMOTHERAPY AND PHARMACOLOGY

Influence of interleukin-6 on the pharmacokinetics and pharmacodynamics of osimertinib in patients with non-small cell lung cancer

Article

Author: Yokota, Hayato ; Akamine, Yumiko ; Nakayama, Katsutoshi ; Sakamoto, Sho ; Miura, Masatomo ; Sato, Kazuhiro ; Takeda, Masahide ; Okuda, Yuji

Abstract:

Purpose:

The inflammatory cytokine interleukin (IL)-6 reduces the activity of drug metabolic enzymes and promotes tumor progression. We investigated the effect of IL-6 on the pharmacokinetics of osimertinib and the association between an IL-6 polymorphism and clinical outcomes in 30 patients with non-small cell lung cancer (NSCLC).

Methods:

Osimertinib and IL-6 plasma concentrations were measured on day 15 after therapy initiation. The genotype of IL-6 1800796G > C was identified using polymerase chain reaction–restriction fragment length polymorphism. Risk factors affecting overall survival (OS) were assessed by Cox proportional hazard regression analysis.

Results:

The IL-6 concentration was significantly correlated with the osimertinib trough plasma concentration (r = 0.423, P = 0.020) and area under the plasma concentration–time curve (r = 0.420, P = 0.021). The IL-6 concentration was significantly higher in patients with the IL-6 rs1800796G allele versus C/C genotype (P = 0.024). OS was significantly shorter in patients with the IL-6 rs1800796G allele versus C/C genotype (median: 15.1 vs. 48.9 months, P = 0.005). Univariate and multivariate analyses indicated that the IL-6 rs1800796G allele is an independent risk factor for OS (crude hazard ratio = 7.07; P = 0.014; adjusted hazard ratio = 6.38; P = 0.021).

Conclusion:

A higher IL-6 concentration was associated with reduced metabolic activity of osimertinib, leading to increased osimertinib exposure. As the IL-6 concentration was higher in NSCLC patients with the IL-6 rs1800796G allele, it might be an independent prognostic factor for patients treated with osimertinib.

01 Jul 2025·DRUG RESISTANCE UPDATES

CD105 blockade restores osimertinib sensitivity in drug-resistant EGFR-mutant non-small cell lung cancer

Article

Author: Sankar, Kamya ; Li, Xiamo ; Thiruvalluvan, Manish ; Araña, Manuel ; Gayhart, Matthew ; Billet, Sandrine ; Villamejor, Anton L ; Waissengrin, Barliz ; You, Sungyong ; Reckamp, Karen L ; Bhowmick, Neil A ; Lopategui, Jean ; Lownik, Joseph ; Milshteyn, Larry ; Liu, Zhenqiu ; Posadas, Edwin M ; Kim, Hyoyoung

AIM:

To investigate the role of CD105 in mediating drug resistance to EGFR-targeted therapy in non-small cell lung cancer (NSCLC).

METHODS:

Imaging mass cytometry was conducted on 66 NSCLC tumors, 44 of which had EGFR mutations. We correlated clinical variables, including overall survival, with CD105 (endoglin) expression, a co-receptor for bone morphogenetic protein (BMP) signaling. Two osimertinib-resistant EGFR-mutant cell lines were developed to study the effects of EGFR and CD105 disruption. Single cell RNA sequencing of the isogenic parental and osimertinib resistant lines was performed. Additionally, ATAC sequencing and Single Cell ENergetIc metabolism by profiling Translation inHibition analysis (SCENITH) was used to assess promoter chromatin status and glycolytic state.

RESULTS:

We found a negative correlation between CD105 expression and overall survival in patients. Treatment with osimertinib or EGFR knockdown significantly elevated CD105 expression in EGFR-mutant cell lines. Single-cell RNA sequencing identified a subset of cells with heightened endothelial characteristics and altered pyrimidine metabolism, associated with osimertinib resistance. These cells exhibited a slow-cycling behavior, characterized by elevated chromatin condensation and reduced glycolysis. Combining osimertinib with carotuximab, a CD105 neutralizing antibody, significantly reduced the slow-cycling transcriptomic signature, increased chromatin accessibility, and restored glycolysis compared to osimertinib treatment alone. Mass spectrometry confirmed that carotuximab re-engaged EGFR signaling by coupling it with CD105. Consequently, carotuximab re-sensitized resistant tumors to osimertinib by increasing their mitotic index and ERK signaling in mouse models.

CONCLUSION:

Carotuximab effectively reduced the slow-cycling cell population and restored osimertinib sensitivity, offering a promising strategy for managing refractory NSCLC.

761

News (Medical) associated with Osimertinib mesylate

07 Apr 2025

·pipelinereview.com

European Commission approves subcutaneous RYBREVANT®▼ (amivantamab) for the treatment of patients with advanced EGFR-mutated non-small cell lung cancer

Subcutaneous (SC) amivantamab offers patients greater convenience, reducing administration time from hours to minutes and with a five-fold reduction in infusion-related reactions compared to the IV formulation 1 European Commission (EC) approval based on positive results from the Phase 3 PALOMA-3 study 1 BEERSE, Belgium I April 07, 2025 I Janssen-Cilag International NV, a Johnson & Johnson company, today announced that the European Commission (EC) has approved an extension of marketing authorisation for a subcutaneous (SC) formulation of RYBREVANT ® (amivantamab), in combination with LAZCLUZE ® (lazertinib) for the first-line treatment of adult patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) exon 19 deletions (ex19del) or exon 21 L858R substitution mutations, and as a monotherapy for the treatment of adult patients with advanced NSCLC with activating EGFR exon 20 insertion mutations after failure of platinum-based therapy. For these indications, it is recommended that SC amivantamab is administered weekly from Weeks 1 to 4 (total of four doses), then every two weeks starting at Week 5 onwards. 1 This approval follows the recent presentation of final overall survival (OS) results from the Phase 3 MARIPOSA study ( NCT04487080 ), at the 2025 European Lung Cancer Congress (ELCC), showing statistically superior OS with intravenous (IV) amivantamab plus lazertinib versus osimertinib monotherapy in the first-line treatment of patients with advanced EGFR ex19del or L858R substitution mutated NSCLC (hazard ratio [HR], 0.75; 95 percent Confidence Interval [CI], 0.61-0.92; P<0.005). 2 “While great strides have been made in the treatment of EGFR-mutated non-small cell lung cancer, a critical need still exists for treatment approaches that are not only effective but also more convenient for patients, while optimising experience in the clinic,” said Silvia Novello, M.D., Ph.D., Professor of Medical Oncology in the Oncology Department at San Luigi Hospital in Orbassano, University of Turin, Italy.* “The approval of subcutaneous amivantamab will have a meaningful impact on clinical practice, offering patients greater convenience and an improved treatment experience, without compromising on the well-established efficacy of intravenous amivantamab.” The EC approval is supported by positive results from the Phase 3 PALOMA-3 study ( NCT05388669 ), which evaluated non-inferiority of pharmacokinetics (PK) in addition to efficacy and safety of SC amivantamab (administered via manual injection) compared to IV amivantamab (the already approved route of administration), both in combination with lazertinib, in patients with EGFR-mutated advanced or metastatic NSCLC after disease progression on osimertinib and platinum-based chemotherapy. 1,3 The study demonstrated that SC amivantamab was non-inferior to IV amivantamab, meeting both co-primary PK endpoints as measured by amivantamab levels in the blood (C trough and area under the serum concentration time curve from Cycle 2 day 1 to 15). 1 At a median follow-up of 7 months, the overall response rate (a secondary endpoint) was 30 percent (95 percent confidence interval [CI], 24–37) in the SC arm and 33 percent (95 percent CI, 26–39) for IV (relative risk, 0.92; 95 percent CI, 0.70–1.23; P =0.001), meeting the non-inferiority criteria. 1 Administration time for SC amivantamab was approximately five minutes, and results showed a five-fold reduction in infusion-related reactions (IRRs) compared to IV administration. 1 These results were featured as an oral presentation at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the Journal of Clinical Oncology . 1,4 “The approval of subcutaneous amivantamab represents a welcome improvement of the treatment experience for both patients living with EGFR-mutated advanced non-small cell lung cancer and the healthcare professionals who support them,” said Henar Hevia, PhD., Senior Director, EMEA Therapeutic Area Lead, Oncology, Johnson & Johnson Innovative Medicine. “This advancement presents an important opportunity to reduce the treatment burden, improve quality of life and give patients more time to focus on what truly matters to them.” The rate of IRRs for patients treated with SC amivantamab combined with lazertinib was shown to be approximately five-fold lower than that observed with the IV formulation (13 percent vs 66 percent, respectively). 1 The majority of IRRs were grades 1 and 2, with one patient experiencing a grade 3 IRR in the SC arm. 1 Preventive blood thinning (prophylactic anticoagulation) was used in most patients in the PALOMA-3 study. 1 Patients receiving prophylactic anticoagulation had lower rates of venous thromboembolic events (VTEs) (10 percent) than those who did not receive prophylaxis (21 percent). 1 Furthermore, VTE incidence was numerically lower in the SC arm vs the IV arm (9 percent vs 14 percent) regardless of anticoagulation status. 1 Severe bleeding risk (grade 3 to 4) was low among patients receiving anticoagulants in both the SC (2 percent) and IV (0.6 percent) arms. 1 Otherwise, the overall safety profile of SC amivantamab is consistent with the known profile of IV administration. 1 The most common all-grade adverse events of any cause that occurred for SC amivantamab compared to IV, were paronychia (54 percent vs 51 percent), hypoalbuminaemia (47 percent vs 37 percent) and rash (46 percent vs 43 percent), respectively. 1 “At Johnson & Johnson, we are dedicated to patient-centered innovation in our mission to address the critical unmet needs in lung cancer treatment and care,” said Joshua Bauml, M.D., Vice President, Lung Cancer Disease Area Stronghold Leader, Johnson & Johnson Innovative Medicine. “Our ongoing focus on advancing the clinical development programme for amivantamab reflects our confidence in its potential to become a standard of care for EGFR-and MET-driven lung cancer.” #ENDS# About Amivantamab Amivantamab is a fully-human EGFR-MET bispecific antibody that acts by targeting tumours with activating and resistance EGFR mutations and MET mutations and amplifications, and by harnessing the immune system. 5,6,7,8 The European Commission (EC) has approved amivantamab in the following indications: 8 Intravenous amivantamab: Subcutaneous amivantamab: The recommended dose regimen for SC amivantamab for these indications is 1600 mg (2240 mg for body weight ≥80kg) administered weekly from Weeks 1 to 4 (total of four doses), then every two weeks starting at Week 5 onwards (Q2W). 8 When given in combination with lazertinib, it is recommended to administer SC amivantamab any time after lazertinib when given on the same day. 8 Subcutaneous amivantamab is co-formulated with recombinant human hyaluronidase PH20 (rHuPH20), Halozyme’s ENHANZE ® drug delivery technology. 1 For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using amivantamab, please refer to the Summary of Product Characteristics . 8 ▼ In line with EMA regulations for new medicines, amivantamab is subject to additional monitoring. About Lazertinib In 2018, Janssen Biotech, Inc. entered into a license and collaboration agreement with Yuhan Corporation for the development of lazertinib. Lazertinib is an oral, third-generation, brain-penetrant EGFR tyrosine kinase inhibitor (TKI) that targets both the T790M mutation and activating EGFR mutations while sparing wild-type EGFR. 9 An analysis of the efficacy and safety of lazertinib from the Phase 3 study LASER301 was published in The Journal of Clinical Oncology in 2023. 9 In January 2025, the European Commission EC approved a marketing authorisation for lazertinib, in combination with amivantamab, for the first-line treatment of adult patients with advanced NSCLC with EGFR exon 19 deletion or exon 21 L858R substitution mutations. 10 For a full list of adverse events and information on dosage and administration, contraindications and other precautions when using lazertinib, please refer to the Summary of Product Characteristics . 11 ▼ In line with EMA regulations for new medicines, lazertinib is subject to additional monitoring. About PALOMA-3 PALOMA-3 ( NCT05388669 ), which enrolled 418 patients, is a randomised, open-label Phase 3 study evaluating the non-inferiority of pharmacokinetics (PK), efficacy and safety of subcutaneous amivantamab (administered via manual injection) combined with lazertinib compared to IV amivantamab and lazertinib in patients with EGFR-mutated advanced or metastatic NSCLC after progression on osimertinib and platinum-based chemotherapy. 1 The co-primary PK endpoints of the study were trough concentration (C trough on Cycle [C] 2 Day [D] 1 or C4D1) and C2 area under the curve (AUCD1-D15). 1 Key secondary endpoints were objective response rate (ORR) and progression-free survival (PFS). 1 Overall survival was a predefined exploratory endpoint. 1 Prophylactic anticoagulation was recommended for the first four months of treatment. 1 About Non-Small Cell Lung Cancer In Europe, it is estimated that 484,306 people were diagnosed with lung cancer in 2022. 12 NSCLC accounts for 85 percent of all lung cancer cases. 13 Lung cancer is Europe’s biggest cancer killer, with more deaths than breast cancer and prostate cancer combined. 12 The main subtypes of NSCLC are adenocarcinoma, squamous cell carcinoma and large cell carcinoma. 13 Among the most common driver mutations in NSCLC are alterations in EGFR, which is a receptor tyrosine kinase controlling cell growth and division. 13,14 EGFR mutations are present in 10 to 15 percent of Western patients with NSCLC with adenocarcinoma histology and occur in 40 to 50 percent of Asian patients. 15,16,17,18 EGFR ex19del or EGFR exon 21 L858R mutations are the most common EGFR mutations. 19 The five-year survival rate for all patients with advanced NSCLC and EGFR mutations treated with EGFR TKIs is less than 20 percent and between 25-32 percent of patients receiving the current first-line standard of care, osimertinib, do not survive long enough to reach second-line treatment. 20,21,22,23,24,25,26 EGFR exon 20 insertion (ex20ins) mutations are the third most prevalent activating EGFR mutation. 27 Patients with EGFR ex20ins mutations have a real-world five-year OS of eight percent in the frontline setting, which is worse than patients with EGFR ex19del or L858R mutations, who have a real-world five-year OS of 19 percent. 21 About Johnson & Johnson At Johnson & Johnson, we believe health is everything. Our strength in healthcare innovation empowers us to build a world where complex diseases are prevented, treated, and cured, where treatments are smarter and less invasive, and solutions are personal. Through our expertise in Innovative Medicine and MedTech, we are uniquely positioned to innovate across the full spectrum of healthcare solutions today to deliver the breakthroughs of tomorrow and profoundly impact health for humanity. Learn more at https://innovativemedicine.jnj.com/emea/ . Follow us at http://www.linkedin.com/company/jnj-innovative-medicine-emea . Janssen-Cilag International NV, Janssen Research & Development, LLC, Janssen Biotech, Inc. and Janssen-Cilag, S.A. are Johnson & Johnson companies. References 1 Leighl NB et al. Subcutaneous Versus Intravenous Amivantamab, Both in Combination With Lazertinib, in Refractory Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer: Primary Results From the Phase III PALOMA-3 Study. ASCO Journal of Clinical Oncology . 2024;42(3):3593-3605. 2 Yang J, et al. Amivantamab Plus Lazertinib vs Osimertinib in First-line (1L) EGFR-mutant (EGFRm) Advanced NSCLC: Final Overall Survival (OS) from the Phase 3 MARIPOSA Study. 2025 European Lung Cancer Congress. March 26, 2025. 3 ClinicalTrials.gov. A Study of Lazertinib With Subcutaneous Amivantamab Compared With Intravenous Amivantamab in Participants With Epidermal Growth Factor Receptor (EGFR)-Mutated Advanced or Metastatic Non-small Cell Lung Cancer (PALOMA-3). https://clinicaltrials.gov/ct2/show/NCT05388669 . Accessed April 2025. 4 Leighl N, et al. Subcutaneous Amivantamab Plus Lazertinib Vs Intravenous Amivantamab Plus Lazertinib In EGFR-mutated, Advanced Non-small Cell Lung Cancer (NSCLC): PALOMA-3, A Phase 3, Global, Randomized, Controlled Trial. 2024 American Society of Clinical Oncology Annual Meeting. May 31, 2024. 5 Moores SL, et al. A Novel Bispecific Antibody Targeting EGFR and cMet Is Effective against EGFR Inhibitor-Resistant Lung Tumors. Cancer Res 2016;76(13)(suppl 27216193):3942-3953. 6 Grugan KD, et al. Fc-mediated activity of EGFR x c-Met bispecific antibody JNJ-61186372 enhanced killing of lung cancer cells. Mabs . 2017;9(1):114-126. 7 Yun J, et al. Antitumor Activity of Amivantamab (JNJ-61186372), an EGFR–MET Bispecific Antibody, in Diverse Models of EGFR Exon 20 Insertion–Driven NSCLC. Cancer Discov . 2020;10(8):1194-1209. 8 European Medicines Agency. Amivantamab Summary of Product Characteristics. January 2025. Available at: https://www.ema.europa.eu/en/documents/product-information/rybrevant-epar-product-information_en.pdf . Accessed: April 2025. 9 Cho, BC, et al. Lazertinib versus gefitinib as first-line treatment in patients with EGFR -mutated advanced non-small-cell lung cancer: Results From LASER301. J Clin Oncol. 2023;41(26):4208-4217. 10 Innovativemedicine.jnj.com/EMEA. European Commission approves LAZCLUZE®▼ (lazertinib) in combination with RYBREVANT®▼ (amivantamab) for the first-line treatment of patients with EGFR-mutated advanced non-small cell lung cancer. Available at: https://www.jnj.com/media-center/press-releases/european-commission-approves-lazcluze-lazertinib-in-combination-with-rybrevant-amivantamab-for-the-first-line-treatment-of-patients-with-egfr-mutated-advanced-non-small-cell-lung-cancer . Accessed: April 2025 11 European Medicines Agency. Lazcluze. January 2025. Available at: https://www.ema.europa.eu/en/medicines/human/EPAR/lazcluze . Accessed April 2025. 12 Global Cancer Observatory. Cancer Today. Available at: https://gco.iarc.fr/en . Accessed April 2025. 13 Zappa C, et al. Non-small cell lung cancer: current treatment and future advances. Transl Lung Cancer Res . 2016;5(3):288–300. 14 Wee P, Wang Z. Epidermal Growth Factor Receptor Cell Proliferation Signaling Pathways. Cancers. 2017;9(5):52. 15 Pennell NA, et al. A phase II trial pf adjuvant erlotinib in patients with resected epidermal growth factor receptor-mutant non-small cell lung cancer. J Clin Oncol . 2019;37(7);97-104. 16 Burnett H, et al. Epidemiological and clinical burden of EGFR exon 20 insertion in advanced non-small cell lung cancer: a systematic literature review. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 17 Zhang YL, et al. The prevalence of EGFR mutation in patients with non-small cell lung cancer: a systematic review and meta-analysis. Oncotarget . 2016;7(48):78985-78993. 18 Midha A, et al. EGFR mutation incidence in non-small-cell lung cancer of adenocarcinoma histology: a systematic review and global map by ethnicity. Am J Cancer Res . 2015;5(9):2892-2911. 19 American Lung Association. EGFR and Lung Cancer. Available at: https://www.lung.org/lung-health-diseases/lung-disease-lookup/lung-cancer/symptoms-diagnosis/biomarker-testing/egfr . Accessed April 2025. 20 Lin JJ, et al. Five-Year Survival in EGFR-Mutant Metastatic Lung Adenocarcinoma Treated with EGFR-TKIs. J Thorac Oncol 2016 Apr;11(4):556-65. 21 Girard N, et al. Comparative clinical outcomes for patients with NSCLC harboring EGFR exon 20 insertion mutations and common EGFR mutations. Abstract presented at: World Conference on Lung Cancer Annual Meeting; January 29, 2021; Singapore. 22 Shao J et al. The number of brain metastases predicts the survival of non-small cell lung cancer patients with EGFRR mutation status. Cancer Rep (Hoboken). 2022;5(9): e1550. 23 Achrol A et al. Brain metastases. Nat Rev Dis Primers . 2019;17(5): 5. 24 Rangachari D et al. Brain metastases in patients with EGFR-mutated or ALK-rearranged non-small-cell lung cancers. Lung Cancer . 2015;88(1): 108-111. 25 Nieva J, et al. A real-world (rw) observational study of long-term survival (LTS) and treatment patterns after first-line (1L) osimertinib in patients (pts) with epidermal growth factor receptor (EGFR) mutation-positive (m) advanced non-small cell lung cancer (NSCLC). Ann Oncol . 2023;34, S774. 26 Girard N, Leighl NB, Ohe Y, et al. Mortality among EGFR-mutated advanced NSCLC patients after starting frontline osimertinib treatment: a real-world, US attrition analysis. Presented at: the European Lung Cancer Congress; March 29-April 1, 2023; Copenhagen, Denmark. Poster 19P. 27 Arcila, M. et al. EGFR exon 20 insertion mutations in lung adenocarcinomas: prevalence, molecular heterogeneity, and clinicopathologic characteristics. Mol Cancer Ther. 2013 Feb; 12(2):220-9. SOURCE: Johnson & Johnson

Clinical ResultPhase 3ASCODrug ApprovalLicense out/in

04 Apr 2025

·pipelinereview.com

Imfinzi-based perioperative regimen approved in the EU for resectable non-small cell lung cancer

Approval based on AEGEAN Phase III trial results which showed a 32% reduction in the risk of recurrence, progression or death vs. neoadjuvant chemotherapy alone LONDON, UK I April 04, 2025 I AstraZeneca’s Imfinzi (durvalumab) in combination with chemotherapy has been approved in the European Union (EU) for the treatment of adults with resectable non-small cell lung cancer (NSCLC) at high risk of recurrence and no epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. In this regimen, patients are treated with Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery. The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the pivotal AEGEAN trial, which were published in The New England Journal of Medicine . Each year in Europe, there are more than 450,000 people diagnosed with lung cancer. 1 Around 25-30% of all patients with NSCLC, the most common form of lung cancer, are diagnosed at an early stage to have surgery with curative intent. 2-3 However, the majority of patients with resectable disease will develop recurrence and only 36-46% of patients with Stage II disease will survive for five years. 4-5 This decreases to 24% for patients with Stage IIIA disease and 9% for patients with Stage IIIB disease, reflecting a high unmet medical need. 4 Professor Martin Reck, Head of the Department of Thoracic Oncology at the Lung Clinic Grosshansdorf, Germany, member of the AEGEAN Steering Committee and investigator in the trial, said: “Today’s approval provides an important new treatment option that should become a backbone combination approach for patients in Europe with resectable non-small cell lung cancer, who have historically faced high rates of recurrence and a poor prognosis. When added to neoadjuvant chemotherapy, perioperative durvalumab meaningfully improved outcomes in this curative-intent setting, significantly extending the time patients lived without their cancer returning.” Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “Today’s approval marks an important step towards improving outcomes for patients in Europe with resectable non-small cell lung cancer, enabling more patients to access this important immunotherapy-based regimen. This new indication builds on the established role of Imfinzi in unresectable disease and underscores our commitment to transforming care in the early stages of lung cancer where there is the greatest potential for cure.” Results from a planned interim analysis of event-free survival (EFS) showed a statistically significant and clinically meaningful 32% reduction in the risk of recurrence, progression events or death versus neoadjuvant chemotherapy alone in patients treated with the Imfinzi -based perioperative regimen (32% data maturity; EFS hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.53-0.88; p=0.003902). In a final analysis of pathologic complete response (pCR), treatment with Imfinzi plus neoadjuvant chemotherapy before surgery resulted in a pCR rate of 17.2% versus 4.3% for patients treated with neoadjuvant chemotherapy alone (difference in pCR 13.0%; 95% CI 8.7-17.6). Additionally, interim overall survival (OS) results presented at the 2024 World Conference on Lung Cancer showed a favourable trend with the Imfinzi- basedperioperative regimen (35% data maturity; median OS: not reached [NR] versus 53.2 months; HR=0.89; 95% CI 0.70-1.14). The OS data were not tested for statistical significance at this interim analysis and will continue to be assessed as a key secondary endpoint at final analysis. Imfinzi was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients’ ability to complete surgery versus chemotherapy alone. Imfinzi is approved in the US, China and several other countries in this setting based on the AEGEAN results. Regulatory applications are currently under review in Japan and additional countries in this indication. Imfinzi is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease as not progressed after chemoradiotherapy (CRT) based on the PACIFIC Phase III trial. Notes Lung cancer Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths. 6-7 Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC), with 80-85% of patients diagnosed with NSCLC. 8-9 An estimated 28,000 people are treated for resectable NSCLC across the five major European countries each year. 10 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition. 11-12 The majority of patients with resectable disease eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy. 5 AEGEAN AEGEAN is a randomised, double-blind, multi-centre, placebo-controlled global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage IIA-IIIB (Eighth Edition AJCC Cancer Staging Manual) NSCLC, irrespective of PD-L1 expression. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 802 patients were randomised to receive a 1500mg fixed dose of Imfinzi plus chemotherapy or placebo plus chemotherapy every three weeks for four cycles prior to surgery, followed by Imfinzi or placebo every four weeks (for up to 12 cycles) after surgery. Patients with known EGFR or ALK genomic tumour aberrations were excluded from the primary efficacy analyses. In the AEGEAN trial, the primary endpoints were pCR, defined as no viable tumour in the resection specimen (including lymph nodes) following neoadjuvant therapy, and EFS, defined as the time from randomisation to an event like tumour recurrence, progression precluding definitive surgery, or death. Key secondary endpoints were major pathologic response, defined as residual viable tumour of less than or equal to 10% in the resected primary tumour following neoadjuvant therapy, disease-free survival, OS, safety and quality of life. The final pathologic response analyses were performed after all patients had the opportunity for surgery and pathology assessment per the trial protocol. The trial enrolled participants from 264 centres in more than 25 countries including in the US, Canada, Europe, South America and Asia. Imfinzi Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour’s immune-evading tactics and releasing the inhibition of immune responses. In addition to its indications in resectable, early-stage (IIA-IIIB) NSCLC and unresectable, Stage III NSCLC, Imfinzi is also approved for use in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC. Imfinzi is also approved for limited-stage SCLC in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of extensive-stage SCLC. Imfinzi is also approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU. In March 2025, perioperative Imfinzi added to standard-of-care chemotherapy met the primary endpoint of EFS in the MATTERHORN Phase III trial in resectable gastric and gastroesophageal junction cancers. Imfinzi is also approved as a perioperative treatment in combination with neoadjuvant chemotherapy for muscle-invasive bladder cancer in the US. Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US and EU). Imfinzi in combination with chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in EU and Japan. Since the first approval in May 2017, more than 374,000 patients have been treated with Imfinzi . As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumours. 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 (osimertinib) and Iressa (gefitinib); Imfinzi and Imjudo ; Enhertu (trastuzumab deruxtecan) and Datroway (datopotamab deruxtecan) in collaboration with Daiichi Sankyo; Orpathys (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 immuno-oncology (IO) AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours. AstraZeneca strives to redefine cancer care and help transform outcomes for patients with Imfinzi as a monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers. AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure. 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/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, 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 . References 1. Ferlay J, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer . 2018;103:356-387. 2. Cagle PT, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med . 2013;137(9):1191-1198. 3. Le Chevalier T. Adjuvant Chemotherapy for Resectable Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol . 2010;21(suppl 7):vii196-198. 4. Goldstraw P, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol . 2007;2(8):706-14. 5. Pignon JP, et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol . 2008;26(21):3552-3559. 6. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf . Accessed April 2025. 7. World Health Organization. International Agency for Research on Cancer. All Cancers Fact Sheet. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/cancers/39-all-cancers-fact-sheet.pdf . Accessed April 2025. 8. LUNGevity Foundation. Types of Lung Cancer. Available at: https://www.lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer . Accessed April 2025. 9. Cheema PK, et al. Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer. Curr Oncol . 2019;26(1):37-42. 10. AstraZeneca PLC. Investor Relations Epidemiology Spreadsheet. Available at: https://www.astrazeneca.com/investor-relations.html . Accessed April 2025. 11. Sethi S, et al. Incidental Nodule Management – Should There Be a Formal Process? J Thorac Dis . 2016:8(Suppl 6);S494-S497. 12. LUNGevity Foundation. Screening and Early Detection. Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection . Accessed April 2025. SOURCE: AstraZeneca

Clinical ResultPhase 3ImmunotherapyDrug Approval

04 Apr 2025

·www.astrazeneca.com

Imfinzi-based perioperative regimen approved in the EU for resectable non-small cell lung cancer

AstraZeneca’s Imfinzi (durvalumab) in combination with chemotherapy has been approved in the European Union (EU) for the treatment of adults with resectable non-small cell lung cancer (NSCLC) at high risk of recurrence and no epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements. In this regimen, patients are treated with Imfinzi in combination with neoadjuvant chemotherapy before surgery and as adjuvant monotherapy after surgery. The approval by the European Commission follows the positive opinion of the Committee for Medicinal Products for Human Use and is based on results from the pivotal AEGEAN trial, which were published in The New England Journal of Medicine. Each year in Europe, there are more than 450,000 people diagnosed with lung cancer.1 Around 25-30% of all patients with NSCLC, the most common form of lung cancer, are diagnosed at an early stage to have surgery with curative intent.2-3 However, the majority of patients with resectable disease will develop recurrence and only 36-46% of patients with Stage II disease will survive for five years.4-5 This decreases to 24% for patients with Stage IIIA disease and 9% for patients with Stage IIIB disease, reflecting a high unmet medical need.4 Professor Martin Reck, Head of the Department of Thoracic Oncology at the Lung Clinic Grosshansdorf, Germany, member of the AEGEAN Steering Committee and investigator in the trial, said: “Today’s approval provides an important new treatment option that should become a backbone combination approach for patients in Europe with resectable non-small cell lung cancer, who have historically faced high rates of recurrence and a poor prognosis. When added to neoadjuvant chemotherapy, perioperative durvalumab meaningfully improved outcomes in this curative-intent setting, significantly extending the time patients lived without their cancer returning.” Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “Today’s approval marks an important step towards improving outcomes for patients in Europe with resectable non-small cell lung cancer, enabling more patients to access this important immunotherapy-based regimen. This new indication builds on the established role of Imfinzi in unresectable disease and underscores our commitment to transforming care in the early stages of lung cancer where there is the greatest potential for cure.” Results from a planned interim analysis of event-free survival (EFS) showed a statistically significant and clinically meaningful 32% reduction in the risk of recurrence, progression events or death versus neoadjuvant chemotherapy alone in patients treated with the Imfinzi-based perioperative regimen (32% data maturity; EFS hazard ratio [HR] 0.68; 95% confidence interval [CI] 0.53-0.88; p=0.003902). In a final analysis of pathologic complete response (pCR), treatment with Imfinzi plus neoadjuvant chemotherapy before surgery resulted in a pCR rate of 17.2% versus 4.3% for patients treated with neoadjuvant chemotherapy alone (difference in pCR 13.0%; 95% CI 8.7-17.6). Additionally, interim overall survival (OS) results presented at the 2024 World Conference on Lung Cancer showed a favourable trend with the Imfinzi-basedperioperative regimen (35% data maturity; median OS: not reached [NR] versus 53.2 months; HR=0.89; 95% CI 0.70-1.14). The OS data were not tested for statistical significance at this interim analysis and will continue to be assessed as a key secondary endpoint at final analysis. Imfinzi was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding Imfinzi to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients' ability to complete surgery versus chemotherapy alone. Imfinzi is approved in the US, China and several other countries in this setting based on the AEGEAN results. Regulatory applications are currently under review in Japan and additional countries in this indication. Imfinzi is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease as not progressed after chemoradiotherapy (CRT) based on the PACIFIC Phase III trial. Notes Lung cancer Lung cancer is the leading cause of cancer death among both men and women, accounting for about one-fifth of all cancer deaths.6-7 Lung cancer is broadly split into NSCLC and small cell lung cancer (SCLC), with 80-85% of patients diagnosed with NSCLC.8-9 An estimated 28,000 people are treated for resectable NSCLC across the five major European countries each year.10 Early-stage lung cancer diagnoses are often only made when the cancer is found on imaging for an unrelated condition.11-12 The majority of patients with resectable disease eventually develop recurrence despite complete tumour resection and adjuvant chemotherapy.5 AEGEAN AEGEAN is a randomised, double-blind, multi-centre, placebo-controlled global Phase III trial evaluating Imfinzi as perioperative treatment for patients with resectable Stage IIA-IIIB (Eighth Edition AJCC Cancer Staging Manual) NSCLC, irrespective of PD-L1 expression. Perioperative therapy includes treatment before and after surgery, also known as neoadjuvant/adjuvant therapy. In the trial, 802 patients were randomised to receive a 1500mg fixed dose of Imfinzi plus chemotherapy or placebo plus chemotherapy every three weeks for four cycles prior to surgery, followed by Imfinzi or placebo every four weeks (for up to 12 cycles) after surgery. Patients with known EGFR or ALK genomic tumour aberrations were excluded from the primary efficacy analyses. In the AEGEAN trial, the primary endpoints were pCR, defined as no viable tumour in the resection specimen (including lymph nodes) following neoadjuvant therapy, and EFS, defined as the time from randomisation to an event like tumour recurrence, progression precluding definitive surgery, or death. Key secondary endpoints were major pathologic response, defined as residual viable tumour of less than or equal to 10% in the resected primary tumour following neoadjuvant therapy, disease-free survival, OS, safety and quality of life. The final pathologic response analyses were performed after all patients had the opportunity for surgery and pathology assessment per the trial protocol. The trial enrolled participants from 264 centres in more than 25 countries including in the US, Canada, Europe, South America and Asia. Imfinzi Imfinzi (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumour's immune-evading tactics and releasing the inhibition of immune responses. In addition to its indications in resectable, early-stage (IIA-IIIB) NSCLC and unresectable, Stage III NSCLC, Imfinzi is also approved for use in combination with a short course of Imjudo (tremelimumab) and chemotherapy for the treatment of metastatic NSCLC. Imfinzi is also approved for limited-stage SCLC in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of extensive-stage SCLC. Imfinzi is also approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with Imjudo in unresectable hepatocellular carcinoma (HCC). Imfinzi is also approved as a monotherapy in unresectable HCC in Japan and the EU. In March 2025, perioperative Imfinzi added to standard-of-care chemotherapy met the primary endpoint of EFS in the MATTERHORN Phase III trial in resectable gastric and gastroesophageal junction cancers. Imfinzi is also approved as a perioperative treatment in combination with neoadjuvant chemotherapy for muscle-invasive bladder cancer in the US. Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US and EU). Imfinzi in combination with chemotherapy followed by Lynparza (olaparib) and Imfinzi is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in EU and Japan. Since the first approval in May 2017, more than 374,000 patients have been treated with Imfinzi. As part of a broad development programme, Imfinzi is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal and gynaecologic cancers, and other solid tumours. 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 (osimertinib) and Iressa (gefitinib); Imfinzi and Imjudo; Enhertu (trastuzumab deruxtecan) and Datroway (datopotamab deruxtecan) in collaboration with Daiichi Sankyo; Orpathys (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 immuno-oncology (IO) AstraZeneca is a pioneer in introducing the concept of immunotherapy into dedicated clinical areas of high unmet medical need. The Company has a comprehensive and diverse IO portfolio and pipeline anchored in immunotherapies designed to overcome evasion of the anti-tumour immune response and stimulate the body’s immune system to attack tumours. AstraZeneca strives to redefine cancer care and help transform outcomes for patients with Imfinzi as a monotherapy and in combination with Imjudo as well as other novel immunotherapies and modalities. The Company is also investigating next-generation immunotherapies like bispecific antibodies and therapeutics that harness different aspects of immunity to target cancer, including cell therapy and T-cell engagers. AstraZeneca is pursuing an innovative clinical strategy to bring IO-based therapies that deliver long-term survival to new settings across a wide range of cancer types. The Company is focused on exploring novel combination approaches to help prevent treatment resistance and drive longer immune responses. With an extensive clinical programme, the Company also champions the use of IO treatment in earlier disease stages, where there is the greatest potential for cure. 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/Nasdaq: AZN) is a global, science-led biopharmaceutical company that focuses on the discovery, development, and commercialisation of prescription medicines in Oncology, Rare Diseases, 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. Contacts For details on how to contact the Investor Relations Team, please click here. For Media contacts, click here. References 1. Ferlay J, et al. Cancer incidence and mortality patterns in Europe: Estimates for 40 countries and 25 major cancers in 2018. Eur J Cancer. 2018;103:356-387. 2. Cagle PT, et al. Lung Cancer Biomarkers: Present Status and Future Developments. Arch Pathol Lab Med. 2013;137(9):1191-1198. 3. Le Chevalier T. Adjuvant Chemotherapy for Resectable Non-Small-Cell Lung Cancer: Where is it Going? Ann Oncol. 2010;21(suppl 7):vii196-198. 4. Goldstraw P, et al. The IASLC Lung Cancer Staging Project: proposals for the revision of the TNM stage groupings in the forthcoming (seventh) edition of the TNM Classification of malignant tumours. J Thorac Oncol. 2007;2(8):706-14. 5. Pignon JP, et al. Lung Adjuvant Cisplatin Evaluation: A Pooled Analysis by the LACE Collaborative Group. J Clin Oncol. 2008;26(21):3552-3559. 6. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf. Accessed April 2025. 7. World Health Organization. International Agency for Research on Cancer. All Cancers Fact Sheet. Available at: https://gco-iarc-who-int.libproxy1.nus.edu.sg/media/globocan/factsheets/cancers/39-all-cancers-fact-sheet.pdf. Accessed April 2025. 8. LUNGevity Foundation. Types of Lung Cancer. Available at: https://www.lungevity.org/for-patients-caregivers/lung-cancer-101/types-of-lung-cancer. Accessed April 2025. 9. Cheema PK, et al. Perspectives on treatment advances for stage III locally advanced unresectable non-small-cell lung cancer. Curr Oncol. 2019;26(1):37-42. 10. AstraZeneca PLC. Investor Relations Epidemiology Spreadsheet. Available at: https://www.astrazeneca.com/investor-relations.html. Accessed April 2025. 11. Sethi S, et al. Incidental Nodule Management – Should There Be a Formal Process? J Thorac Dis. 2016:8(Suppl 6);S494-S497. 12. LUNGevity Foundation. Screening and Early Detection. Available at: https://lungevity.org/for-patients-caregivers/lung-cancer-101/screening-early-detection. Accessed April 2025. Adrian Kemp Company Secretary AstraZeneca PLC Oncology Corporate and financial

Clinical ResultImmunotherapyPhase 3Drug Approval

100 Deals associated with Osimertinib mesylate

External Link

KEGG	Wiki	ATC	Drug Bank
D10766	Osimertinib mesylate	L01XE	DB09330

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	Canada	AstraZeneca Canada, Inc.	05 Jul 2016
EGFR positive non-small cell lung cancer	Japan	AstraZeneca Pharmaceuticals Co. Ltd.	28 Mar 2016
EGFR exon 19 Deletions Mutant Non-small Cell Lung Cancer	European Union	AstraZeneca AB	01 Feb 2016
EGFR exon 19 Deletions Mutant Non-small Cell Lung Cancer	Iceland	AstraZeneca AB	01 Feb 2016
EGFR exon 19 Deletions Mutant Non-small Cell Lung Cancer	Liechtenstein	AstraZeneca AB	01 Feb 2016
EGFR exon 19 Deletions Mutant Non-small Cell Lung Cancer	Norway	AstraZeneca AB	01 Feb 2016
EGFR exon 21 Substitution Mutant Non-small Cell Lung Cancer	European Union	AstraZeneca AB	01 Feb 2016
EGFR exon 21 Substitution Mutant Non-small Cell Lung Cancer	Iceland	AstraZeneca AB	01 Feb 2016
EGFR exon 21 Substitution Mutant Non-small Cell Lung Cancer	Liechtenstein	AstraZeneca AB	01 Feb 2016
EGFR exon 21 Substitution Mutant Non-small Cell Lung Cancer	Norway	AstraZeneca AB	01 Feb 2016
EGFR-mutated non-small Cell Lung Cancer	European Union	AstraZeneca AB	01 Feb 2016
EGFR-mutated non-small Cell Lung Cancer	Iceland	AstraZeneca AB	01 Feb 2016
EGFR-mutated non-small Cell Lung Cancer	Liechtenstein	AstraZeneca AB	01 Feb 2016
EGFR-mutated non-small Cell Lung Cancer	Norway	AstraZeneca AB	01 Feb 2016
metastatic non-small cell lung cancer	European Union	AstraZeneca AB	01 Feb 2016
metastatic non-small cell lung cancer	Iceland	AstraZeneca AB	01 Feb 2016
metastatic non-small cell lung cancer	Liechtenstein	AstraZeneca AB	01 Feb 2016
metastatic non-small cell lung cancer	Norway	AstraZeneca AB	01 Feb 2016
EGFR T790M Mutation Positive Non-Small Cell Lung Carcinoma	United States	AstraZeneca Pharmaceuticals LP	13 Nov 2015

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Neoplasms	Phase 3	United States	AstraZeneca PLC	08 May 2023
Neoplasms	Phase 3	China	AstraZeneca PLC	08 May 2023
Neoplasms	Phase 3	France	AstraZeneca PLC	08 May 2023
Neoplasms	Phase 3	Malaysia	AstraZeneca PLC	08 May 2023
Neoplasms	Phase 3	Poland	AstraZeneca PLC	08 May 2023
Neoplasms	Phase 3	Taiwan Province	AstraZeneca PLC	08 May 2023
Neoplasms	Phase 3	United Kingdom	AstraZeneca PLC	08 May 2023
Carcinoma	Phase 3	United States	AstraZeneca PLC	03 Aug 2022
Carcinoma	Phase 3	China	AstraZeneca PLC	03 Aug 2022
Carcinoma	Phase 3	Japan	AstraZeneca PLC	03 Aug 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT02296125 (FLAURA, AACR2025)	Phase 3	First line EGFRm	127	Osimertinib 80 mg once daily	kvlercgdmo(krdgiuvmdk) = tjvimprixz jdwlbhpbsn (wybysdbuhj ) View more	Positive	28 Apr 2025
				Comparator EGFR-TKI (gefitinib or erlotinib)	kvlercgdmo(krdgiuvmdk) = uglhzjeoxo jdwlbhpbsn (wybysdbuhj ) View more
NCT03778229 (SAVANNAH, ESMO_ELCC2025) Manual	Phase 2	EGFR positive non-small cell lung cancer Second line MET Overexpression \| MET Amplification \| EGFR Mutation	101	Savolitinib 300 mg BID + Osimertinib 80 mg QD	fwjqsaxyml(skjzwqnpka) = pcrakhgmpx emzluimihz (zfpuwufpch, 45 - 67) View more	Positive	26 Mar 2025
OSIREAL study (ESMO_ELCC2025)	Not Applicable	Non-Small Cell Lung Cancer First line EGFR mutations	326	Osimertinib monotherapy	yauugjghmj(ktosjrpchb) = gofqwaleug vtwlguknjv (qzykjowvzh, 13.9 - 18.5)	Positive	26 Mar 2025
NCT03944772 (ORCHARD, ESMO_ELCC2025)	Phase 2	Advanced Lung Non-Small Cell Carcinoma EGFRm	69	Osimertinib (80 mg QD) + Datopotamab Deruxtecan (4 mg/kg Q3W)	sekhsxayle(dpqccbinjh) = yudozsmdhj melktpyqvx (wsllzvmaas ) View more	Positive	26 Mar 2025
				Osimertinib (80 mg QD) + Datopotamab Deruxtecan (6 mg/kg Q3W)	sekhsxayle(dpqccbinjh) = wtagkptuzq melktpyqvx (wsllzvmaas ) View more
ESMO_ELCC2025	Not Applicable	EGFR-mutated non-small Cell Lung Cancer EGFR-TKI-sensitizing mutations \| EGFR-T790M resistance mutation \| exon 19 deletions ... View more	1,838	Osimertinib plus Chemotherapy	iswilfgfzo(vkhmotgmnx) = rates between 20% and 83.8% fjgklrzwek (vuhklnihnz ) View more	Positive	26 Mar 2025
NCT04391283 (FLOURISH study, ESMO_ELCC2025)	Not Applicable	EGFR-mutated non-small Cell Lung Cancer First line EGFRm	481	Osimertinib	sjelrcvtar(obczqrxxuv) = itqjmjacga yayuybkdpz (fgsrtnesis, 24.3 - 29.7) View more	Positive	26 Mar 2025
NCT04035486 (FLAURA2, ESMO_ELCC2025)	Phase 3	Maintenance Ex19del/L858R	279	Osimertinib + Platinum-Pemetrexed	cqwopeqlfk(hutmboiihg) = ivshxufgrv wmssdllrmn (rftqahrwzc, 19.6 - NC) View more	Positive	26 Mar 2025
				Osimertinib	eamikznvrf(mrhdxhvrgm) = kbnfmrovhj dynrtgwjzh (fclruljzta )
NCT03521154 (LAURA study, ESMO_ELCC2025)	Phase 3	Non-small cell lung cancer stage IIIB \| Non-small cell lung cancer stage III \| Unresectable Lung Non-Small Cell Carcinoma ... EGFRm View more	-	Osimertinib	rbohaiiqfc(jtbwutntoc): HR = 0.16 (95% CI, 0.1 - 0.24), P-Value = < 0.001	Positive	26 Mar 2025
				Placebo
ESMO_ELCC2025	Not Applicable	Advanced Lung Non-Small Cell Carcinoma First line EGFRm (Ex19del/L858R)	88	Platinum-based chemotherapy	tpzqglgald(rsgcsfdusr) = ezqycexzfb ckzbykmldr (xsghrsjafl )	Positive	26 Mar 2025
				Immunotherapy-based regimens	tpzqglgald(rsgcsfdusr) = sjbcyototh ckzbykmldr (xsghrsjafl )
ESMO_ELCC2025	Not Applicable	EGFR positive non-small cell lung cancer Adjuvant	-	Patients taking Osimertinib as prescribed	dondpxsnvi(tofebyvzgr) = iazojfsbat secuaamddj (cxtgkjzcki, 1 - 20)	-	26 Mar 2025

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