On August 17, 2026 Astrazeneca and Daiichi Sankyo reported positive high-level results from the DESTINY-Lung04 Phase III trial showed Enhertu (trastuzumab deruxtecan) demonstrated a statistically significant and clinically meaningful improvement in progression-free survival (PFS) versus global standard of care (platinum-pemetrexed doublet chemotherapy plus pembrolizumab) as 1st-line treatment of patients with unresectable, locally advanced or metastatic HER2-mutant non-squamous non-small cell lung cancer (NSCLC). The trial will continue as planned to evaluate secondary endpoints including overall survival.

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The global standard of care for patients with HER2-mutant NSCLC in the 1st-line metastatic setting is a combination of immunotherapy and platinum-based chemotherapy.1-3 However, many patients do not respond to 1st-line treatment and experience disease progression, underscoring the need for additional treatment options.3-7 Approximately 2-4% of patients with NSCLC have tumours with a HER2 mutation.8-10

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "Our oncology pipeline continues to advance with DESTINY-Lung04 becoming the first Phase III trial to demonstrate a progression-free survival benefit versus the global standard of care in this first-line setting, supporting the potential for Enhertu to move earlier in the treatment of HER2-mutant non-small cell lung cancer. This aggressive lung cancer often affects younger patients and has historically had limited first-line targeted treatment options, making these positive results an important step forward in bringing additional effective therapies to patients at metastatic diagnosis when there is the greatest opportunity to improve outcomes."

John Tsai, Global Head, R&D, Daiichi Sankyo, said: "Enhertu is already established as the first and only antibody drug conjugate for the second-line treatment of HER2-mutant metastatic non-small cell lung cancer. The positive results seen in DESTINY-Lung04 show that treatment with Enhertu in the first-line setting delays disease progression compared to the global standard of care, highlighting its potential to improve outcomes for patients earlier in the treatment of metastatic disease."

The safety profile of Enhertu observed in DESTINY-Lung04 was generally consistent with its known profile, with no new safety concerns identified.

The DESTINY-Lung04 data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

Enhertu is currently approved to treat patients with previously treated metastatic NSCLC whose tumours have activating HER2 (ERBB2) mutations, and to treat patients with HER2-positive solid tumours, including HER2-overexpressing metastatic NSCLC, who have received prior treatment and who have no satisfactory treatment options.

Enhertu is a specifically engineered HER2-directed DXd antibody drug conjugate (ADC) discovered by Daiichi Sankyo and being jointly developed and commercialised by AstraZeneca and Daiichi Sankyo.

Notes

HER2-mutant NSCLC
Lung cancer is the most commonly diagnosed cancer globally and remains the leading cause of cancer-related death in both men and women.11 In 2024, approximately 2.6 million new lung cancer cases were reported worldwide, with an estimated 1.8 million deaths.11 NSCLC is the most common type of lung cancer, accounting for approximately 85% of cases.12 Prognosis is particularly poor for patients with metastatic NSCLC as only approximately 10% will live beyond five years after diagnosis.13-15

HER2 is a tyrosine kinase receptor protein involved in cell growth and differentiation and expressed on the surface of multiple tumour types. HER2 mutations have been identified in NSCLC as distinct molecular targets and have been reported in approximately 2-4% of patients with non-squamous NSCLC.8-10 These HER2 mutations are predominantly seen in younger women and people with no smoking history and have been independently associated with cancer cell growth and poor prognosis, with an increased incidence of brain metastases.8,16-20

The global standard of care in the 1st-line metastatic setting for patients with HER2-mutant NSCLC is a combination of immunotherapy and platinum-based chemotherapy.1-3 While these treatment regimens have been shown to improve survival in NSCLC, many patients do not respond to 1st-line treatment and experience disease progression, underscoring the need for additional treatment options.3-7

DESTINY-Lung04
DESTINY-Lung04 is a global, randomised, open-label, Phase III trial evaluating the efficacy and safety of Enhertu (5.4mg/kg) compared to standard of care (platinum-pemetrexed doublet chemotherapy in combination with pembrolizumab) in patients with unresectable, locally advanced or metastatic, non-squamous NSCLC harbouring a HER2 exon 19 or 20 mutation.

Patients were randomised 1:1 to receive either Enhertu or standard of care. Randomisation was stratified by smoking history and presence or history of brain metastasis. The primary endpoint of DESTINY-Lung04 is PFS as assessed by blinded independent central review (BICR). Secondary endpoints include OS, investigator-assessed PFS, overall response rate and duration of response as assessed by BICR and investigator, pharmacokinetics and safety.

DESTINY-Lung04 enrolled 454 patients across multiple sites in Asia, Europe and North America. For more information about the trial, visit ClinicalTrials.gov.

Enhertu
Enhertu is a HER2-directed ADC. Designed using the proprietary DXd ADC Technology of Daiichi Sankyo, Enhertu is the lead ADC in the oncology portfolio of Daiichi Sankyo and the most advanced programme in AstraZeneca’s ADC scientific platform. Enhertu consists of a HER2 monoclonal antibody attached to a number of topoisomerase I inhibitor payloads (an exatecan derivative, DXd) via tetrapeptide-based cleavable linkers.

Enhertu (5.4mg/kg) followed by THP is approved in the US, China, Singapore and India as a neoadjuvant treatment for adult patients with HER2-positive (IHC 3+ or ISH+) Stage II or III breast cancer based on the results from the DESTINY-Breast11 trial. Continued approval in China for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (5.4mg/kg) is approved in Brazil and the US as an adjuvant treatment for adult patients with HER2-positive (IHC 3+ or ISH+) breast cancer who have residual invasive disease following trastuzumab (with or without pertuzumab) and taxane-based treatment based on the DESTINY-Breast05 trial.

Enhertu (5.4mg/kg) in combination with pertuzumab is approved in more than ten countries as a 1st-line treatment for adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer based on the results from the DESTINY-Breast09 trial.

Enhertu (5.4mg/kg) is approved in more than 75 countries worldwide for the treatment of adult patients with unresectable or metastatic hormone receptor (HR)-positive, HER2-low (IHC 1+ or IHC 2+/ ISH-) or HER2-ultralow (IHC 0 with membrane staining) breast cancer, as determined by a locally or regionally authorised test, that have progressed on one or more endocrine therapies in the metastatic setting based on the results from the DESTINY-Breast06 trial.

Enhertu (5.4mg/kg) is approved in more than 100 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+ or ISH+) breast cancer who have received a prior anti-HER2-based regimen, either in the metastatic setting or in the neoadjuvant or adjuvant setting, and have developed disease recurrence during or within six months of completing therapy based on the results from the DESTINY-Breast03 trial.

Enhertu (5.4mg/kg) is approved in more than 100 countries worldwide for the treatment of adult patients with unresectable or metastatic HER2-low (IHC 1+ or IHC 2+/ISH) breast cancer who have received a prior systemic therapy in the metastatic setting or developed disease recurrence during or within six months of completing adjuvant chemotherapy based on the results from the DESTINY-Breast04 trial.

Enhertu (5.4mg/kg) is approved in more than 80 countries worldwide for the treatment of adult patients with unresectable or metastatic non-small cell lung cancer (NSCLC) whose tumours have activating HER2 (ERBB2) mutations, as detected by a locally or regionally approved test, and who have received a prior systemic therapy based on the results from the DESTINY-Lung02 and/or DESTINY-Lung05 trials. Continued approval in China and the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu (6.4mg/kg) is approved in more than 90 countries worldwide for the treatment of adult patients with locally advanced or metastatic HER2-positive (IHC 3+ or IHC 2+/ISH+) gastric or gastroesophageal junction (GEJ) adenocarcinoma who have received a prior trastuzumab-based regimen based on the results from the DESTINY-Gastric01, DESTINY-Gastric02 and/or DESTINY-Gastric04 trials.

Enhertu (5.4mg/kg) is approved in more than 45 countries/regions worldwide for the treatment of adult patients with unresectable or metastatic HER2-positive (IHC 3+) solid tumours who have received prior systemic treatment and have no satisfactory alternative treatment options based on efficacy results from the DESTINY-PanTumor02, DESTINY-Lung01, DESTINY-CRC02 and/or HERALD trials. Continued approval in the US for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial.

Enhertu clinical development programme
A comprehensive global clinical development programme is underway evaluating the efficacy and safety of Enhertu as a monotherapy, in combination or sequentially with other cancer medicines across multiple HER2-targetable cancers.

(Press release, AstraZeneca, AUG 17, 2026, View Source [SID1234670187])

On August 17, 2026 AstraZeneca reported it is discontinuing the eVOLVE-Lung02 Phase III trial evaluating volrustomig in combination with chemotherapy as a 1st-line therapy compared to pembrolizumab and chemotherapy in patients with metastatic non-small cell lung cancer (mNSCLC) whose tumours express PD-L1 <50%.

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This decision is based on the recommendation of the Independent Data Monitoring Committee (IDMC) following a planned review of trial data. The IDMC concluded that the volrustomig combination was unlikely to meet either of the dual primary endpoints of progression-free survival (PFS) or overall survival (OS) in the primary analysis population of patients with PD-L1 negative tumours (<1%) versus the comparator arm.

The safety profile of volrustomig plus chemotherapy was consistent with the known profiles of the individual medicines and no new safety signals were identified.

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "We initiated the eVOLVE-Lung02 trial aiming to improve the outcomes for patients whose lung cancers have lower PD-L1 expression and a less durable response to current immunotherapy regimens. While we are disappointed, we will learn from this trial and are determined to continue pioneering new medicines from our industry-leading pipeline in our quest to improve outcomes for patients with lung cancer."

The Company will work with investigators to ensure continuity of care and appropriate follow up for patients on the trial. The other Phase III volrustomig trials continue as planned in cervical cancer, head and neck squamous cell carcinoma and mesothelioma.

Notes

NSCLC
Lung cancer is the leading cause of death by cancer globally, accounting for almost one in four (23%) cancer deaths.1 Lung cancer is broadly split into small cell lung cancer or NSCLC, the latter accounting for 80-85% of cases.1-2 Patients are most commonly diagnosed with metastatic disease, when the tumour has spread outside the lung.3 Approximately 12% of people with metastatic NSCLC will still be alive five years after diagnosis.4

eVOLVE-Lung02
eVOLVE-Lung02 is a randomized, open-label, multi-centre, global Phase III trial of volrustomig plus chemotherapy for 1st-line treatment of patients with mNSCLC whose tumours express PD-L1 <50%. Patients were randomized 1:1 to receive 750mg intravenous volrustomig in combination with chemotherapy every three weeks for four cycles followed by volrustomig every three weeks, or 200mg pembrolizumab plus chemotherapy every three weeks for four cycles followed by pembrolizumab every three weeks until completion of 24 months of treatment or disease progression, or other discontinuation criterion are met.

The trial enrolled 895 patients across 25 countries. The dual primary endpoints were progression-free survival (PFS) and overall survival (OS) in patients whose tumours express PD-L1 <1%. Secondary endpoints included PFS and OS in the intent-to-treat population (PD-L1 <50%).

Volrustomig
Volrustomig is a dual checkpoint inhibitor bispecific antibody designed to deliver coordinated and targeted PD-1 and CTLA-4 blockade on the same T cell. AstraZeneca is evaluating volrustomig as monotherapy and in combinations in several tumour types with high unmet need.

(Press release, AstraZeneca, AUG 17, 2026, View Source [SID1234670188])

On August 17, 2026 Defence Therapeutics Inc. ("Defence" or the "Company"), (CSE: DTC, OTCQB: DTCFF, FSE: DTC), a publicly traded biotechnology company developing next-generation precision oncology therapeutics using its proprietary Accum technology, reported the appointment of Ryan Simms, PhD, as Chief Operating Officer ("COO") and Head of Radiopharmaceutical Programs, strengthening the Company’s leadership and development capabilities as it advances its radiopharmaceutical drug conjugate ("RDC") programs.

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"Ryan brings more than 20 years of experience in advancing targeted radiopharmaceuticals from discovery through first-in-human clinical studies, combined with the operational leadership needed to translate complex science into executable development programs," said Dr. Amie Phinney, President and Chief Executive Officer of Defence Therapeutics. "His expertise will be instrumental in accelerating our radiopharmaceutical programs and expanding the potential of the Accum platform."

Dr. Simms brings extensive experience in radiopharmaceutical development and operations, with a track record spanning the advancement of targeted radiopharmaceuticals from discovery through clinical development. He held key leadership roles at Fusion Pharmaceuticals, where he directed chemistry, radiochemistry, clinical manufacturing and external partnerships supporting multiple clinical-stage programs. Fusion Pharmaceuticals became a leading player in targeted radiopharmaceuticals and was acquired by AstraZeneca in 2024 for approximately US$2 billion.

Dr. Simms also held leadership roles at Abdera Therapeutics and the Centre for Probe Development and Commercialization (CPDC), building expertise across CMC strategy, manufacturing, isotope supply, radiochemistry and technical operations. This combination of scientific, development and operational experience will support his broader responsibilities as COO as Defence scales its radiopharmaceutical programs and operations. Dr. Simms holds a PhD in Engineering from Queen’s University and completed postdoctoral research in Chemistry at the University of Toronto.

"I am excited to join Defence at a time when the Company is expanding its capabilities and ambitions in radiopharmaceuticals," said Dr. Simms. "We have promising candidates in development and a clear path to advance them. Our immediate priority is to select a lead candidate and move it systematically through preclinical characterization, while establishing the CMC and manufacturing framework required to support its progression toward the clinic. More details will come soon."

Dr. Simms’ appointment follows the recent appointment of Dr. Amie Phinney as President and CEO and the opening of Defence’s new office at McMaster Innovation Park in Hamilton, at the heart of one of Canada’s leading radiopharmaceutical ecosystems. Together, these milestones position Defence for its next phase of growth.

(Press release, Defence Therapeutics, AUG 17, 2026, View Source;utm_medium=rss&utm_campaign=defence-therapeutics-strengthens-radiopharmaceutical-leadership-with-appointment-of-dr-ryan-simms-as-chief-operating-officer-and-head-of-radiopharmaceutical-programs [SID1234670227])

On August 17, 2026 Astrazeneca reported that positive high-level results from the SAFFRON Phase III trial showed Tagrisso (osimertinib) plus Orpathys (savolitinib) demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival (PFS) and overall survival (OS) versus doublet platinum-based chemotherapy in patients with epidermal growth factor receptor-mutated (EGFRm) non-small cell lung cancer (NSCLC). Patients in the trial had tumours with high levels of MET overexpression or amplification and had progressed on prior treatment with Tagrisso.

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Third-generation EGFR-tyrosine kinase inhibitors (TKIs) have significantly improved outcomes for patients with EGFRm NSCLC.1 However, one in three patients’ tumours will develop MET overexpression or amplification, one of the most common mechanisms of resistance on third-generation EGFR-TKIs.1-2 MET-driven resistance is associated with poor prognosis, and there is a significant unmet need for effective and well-tolerated treatment options in later-line settings.2

Professor Shun Lu, Director of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine and principal investigator of the trial, said: "These exciting results from SAFFRON represent a critical advance for patients with EGFR-mutated non-small cell lung cancer experiencing MET-driven resistance after osimertinib, a population with poor outcomes and no biomarker-directed treatment options available that are oral and well-tolerated. MET is one of the most common drivers of progression on targeted therapy in this setting, and these data underscore the potential impact of this novel osimertinib plus savolitinib combination and the urgency of MET testing to inform treatment decisions."​ ​

Susan Galbraith, Executive Vice President, Oncology Haematology R&D, AstraZeneca, said: "These data demonstrate the clear benefit of adding Orpathys to backbone therapy Tagrisso to address MET overexpression or amplification while maintaining EGFR suppression. By combining Orpathys and Tagrisso, with its established efficacy, safety profile and central nervous system protection, we aim to deliver the first biomarker-directed, all-oral option in this setting to patients across the globe. This further strengthens our leadership in EGFR-mutated lung cancer, reinforcing our strategy to improve patient outcomes across stages and through lines of therapy with novel combinations."

Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED, said: "Overcoming MET-driven resistance after EGFR-TKI therapy has been a long-standing challenge in clinical practice. The SAFFRON global study further reinforces the robust efficacy previously demonstrated in the SACHI Phase III trial that supported approval in China, with the results providing clear evidence to support global registrations of the Tagrisso and Orpathys combination. We are grateful to everyone who supported this trial. Together with AstraZeneca, we look forward to potentially bringing this landmark treatment to patients around the world."

The safety profile for Tagrisso plus Orpathys was consistent with the known profiles of each medicine, and there were no new safety findings. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

Tagrisso plus Orpathys is approved in China for patients with locally advanced or metastatic EGFRm NSCLC with MET amplification after disease progression on EGFR-TKI therapy based on the SACHI Phase III trial.

Orpathys is being jointly developed by AstraZeneca and HUTCHMED and commercialised by AstraZeneca.

Notes

NSCLC and MET aberrations
Lung cancer is the leading cause of cancer death globally, accounting for almost one in four (23%) cancer deaths.3 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% of patients diagnosed with NSCLC.4 Approximately 75% of NSCLC patients are diagnosed with advanced disease.5 Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia, have EGFRm NSCLC.​6-8

MET is a tyrosine kinase receptor that has an essential role in normal cell development.9 MET overexpression or amplification can lead to tumour growth and the metastatic progression of cancer cells.9-10 An estimated 34% of tumours will develop high levels of MET overexpression or amplification after progression on a third-generation EGFR-TKI.1 ​

SAFFRON
SAFFRON is a randomised, open-label, multi-centre, global Phase III trial studying the efficacy of Orpathys (300mg twice daily) added to Tagrisso (80mg once daily) versus doublet platinum-based chemotherapy in 338 patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression or amplification whose disease progressed following 1st- or 2nd-line treatment with Tagrisso. The trial enrolled patients in 230 centres across 29 countries, including in North America, Europe, South America and Asia. The primary endpoint is PFS and key secondary endpoints include OS and objective response rate.

Patients were prospectively selected for SAFFRON using the high MET level cut-offs identified in the SAVANNAH Phase II trial.​ In SAVANNAH, MET overexpression or amplification levels were determined by two tests: immunohistochemistry (IHC), which detects if cancer cells have a particular protein or marker on their surface, and fluorescence in situ hybridisation (FISH), which detects a specific DNA sequence from cancer cells.

Orpathys
Orpathys (savolitinib) is an oral, potent and highly selective MET-TKI that has demonstrated clinical activity in advanced solid tumours. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

Orpathys is approved in China for the treatment of adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alteration, representing the first selective MET inhibitor approved in China. Orpathys also received a conditional approval in China for the treatment of patients with locally advanced or metastatic gastric cancer or gastroesophageal junction adenocarcinoma with MET amplification who have failed at least two prior systemic treatments.

Orpathys in combination with Tagrisso is approved in China for patients with locally advanced or metastatic EGFRm-positive non-squamous NSCLC with MET amplification after disease progression on EGFR-TKI therapy based on the SACHI Phase III trial. The combination was also granted a temporary authorisation in Switzerland for the treatment of patients with locally advanced or metastatic EGFRm NSCLC and high levels of MET overexpression or amplification who progressed on prior treatment with Tagrisso. This was based on results from the global SAVANNAH Phase II trial.

Tagrisso
Tagrisso (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including the treatment of central nervous system metastases. Tagrisso (40mg and 80mg QD oral tablets) has been used to treat more than one million patients across its indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFRm NSCLC.

Tagrisso is approved as monotherapy in more than 120 countries including the US, EU, China and Japan. Approved indications include for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, adjuvant treatment of early-stage EGFRm NSCLC and locally advanced, unresectable NSCLC following platinum-based chemoradiation therapy. Tagrisso is also approved in combination with chemotherapy in more than 80 countries, including the US, EU, China and Japan, for 1st-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.

There is an extensive body of evidence supporting the use of Tagrisso in EGFRm NSCLC, and it is the only targeted therapy shown to improve patient outcomes across all stages of the disease.

In late-stage disease, Tagrisso demonstrated improved outcomes as monotherapy in the FLAURA Phase III trial and in combination with chemotherapy in the FLAURA2 Phase III trial. Tagrisso is also being investigated in this setting in combination with Datroway (datopotamab deruxtecan or Dato-DXd) in the TROPION-Lung14 and TROPION-Lung15 Phase III trials.

Tagrisso also showed improved outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials and in locally advanced stages in the LAURA 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 early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

(Press release, AstraZeneca, AUG 17, 2026, View Source [SID1234670189])

On August 16, 2026 HUTCHMED (China) Limited ("HUTCHMED") (Nasdaq/AIM:HCM; HKEX:13) reported that positive high-level results from the SAFFRON Phase III trial showed ORPATHYS (savolitinib) plus TAGRISSO (osimertinib) demonstrated a statistically significant and clinically meaningful improvement in both progression-free survival ("PFS") and overall survival ("OS") versus doublet platinum-based chemotherapy in patients with epidermal growth factor receptor-mutated ("EGFRm") non-small cell lung cancer ("NSCLC"). Patients in the trial had tumors with high levels of MET overexpression or amplification and had progressed on prior treatment with TAGRISSO.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Third-generation EGFR-tyrosine kinase inhibitors ("TKIs") have significantly improved outcomes for patients with EGFRm NSCLC.1 However, one in three patients’ tumors will develop MET overexpression or amplification, one of the most common mechanisms of resistance on third-generation EGFR-TKIs.1,2 MET-driven resistance is associated with poor prognosis, and there is a significant unmet need for effective and well-tolerated treatment options in later-line settings.2

Professor Shun Lu, Director of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, School of Medicine and principal investigator of the trial, said: "These exciting results from SAFFRON represent a critical advance for patients with EGFR-mutated non-small cell lung cancer experiencing MET-driven resistance after osimertinib, a population with poor outcomes and no biomarker-directed treatment options available that are oral and well-tolerated. MET is one of the most common drivers of progression on targeted therapy in this setting, and these data underscore the potential impact of this novel osimertinib plus savolitinib combination and the urgency of MET testing to inform treatment decisions."​

Dr Weiguo Su, Chief Executive Officer* and Chief Scientific Officer of HUTCHMED, said: "Overcoming MET-driven resistance after EGFR TKI therapy has been a long-standing challenge in clinical practice. The SAFFRON global study further reinforces the robust efficacy previously demonstrated in the SACHI Phase III trial that supported approval in China, with the results providing clear evidence to support global registrations of the TAGRISSO and ORPATHYS combination. We are grateful to everyone who supported this trial. Together with AstraZeneca, we look forward to potentially bringing this landmark treatment to patients around the world."

Dr Susan Galbraith, Executive Vice President, Oncology Hematology R&D, AstraZeneca, said: "These data demonstrate the clear benefit of adding ORPATHYS to backbone therapy TAGRISSO to address MET overexpression or amplification while maintaining EGFR suppression. By combining ORPATHYS and TAGRISSO, with its established efficacy, safety profile and central nervous system protection, we aim to deliver the first biomarker-directed, all-oral option in this setting to patients across the globe. This further strengthens our leadership in EGFR-mutated lung cancer, reinforcing our strategy to improve patient outcomes across stages and through lines of therapy with novel combinations."

The safety profile for ORPATHYS plus TAGRISSO was consistent with the known profiles of each medicine, and there were no new safety findings. These data will be presented at a forthcoming medical meeting and shared with global regulatory authorities.

ORPATHYS plus TAGRISSO is approved in China for patients with locally advanced or metastatic EGFRm NSCLC with MET amplification after disease progression on EGFR-TKI therapy based on the SACHI Phase III trial.

ORPATHYS is being jointly developed by AstraZeneca and HUTCHMED and commercialized by AstraZeneca.

About NSCLC and MET aberrations

Lung cancer is the leading cause of cancer death globally, accounting for almost one in four (23%) cancer deaths.3 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% of patients diagnosed with NSCLC.4 Approximately 75% of NSCLC patients are diagnosed with advanced disease.5 Additionally, about 10-15% of NSCLC patients in the US and Europe, and 30-40% of patients in Asia, have EGFRm NSCLC.​6,7,8

MET is a tyrosine kinase receptor that has an essential role in normal cell development.9 MET overexpression or amplification can lead to tumor growth and the metastatic progression of cancer cells.9,10 An estimated 34% of tumors will develop high levels of MET overexpression or amplification after progression on a third-generation EGFR TKI.1

About SAFFRON

SAFFRON is a randomized, open-label, multi-center, global Phase III trial studying the efficacy of ORPATHYS (300mg twice daily) added to TAGRISSO (80mg once daily) versus doublet platinum-based chemotherapy in 338 patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression or amplification whose disease progressed following first- or second-line treatment with TAGRISSO. The trial enrolled patients in 230 centers across 29 countries, including in North America, Europe, South America and Asia. The primary endpoint is PFS and key secondary endpoints include OS and objective response rate (ORR).

Patients were prospectively selected for SAFFRON using the high MET level cut-offs identified in the SAVANNAH Phase II trial. ​In SAVANNAH, MET overexpression or amplification levels were determined by two tests: immunohistochemistry (IHC), which detects if cancer cells have a particular protein or marker on their surface, and fluorescence in situ hybridization (FISH), which detects a specific DNA sequence from cancer cells.

About ORPATHYS

ORPATHYS (savolitinib) is an oral, potent and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations), gene amplification or protein overexpression.

ORPATHYS is approved in China for the treatment of adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alteration, representing the first selective MET inhibitor approved in China. ORPATHYS also received a conditional approval in China for the treatment of patients with locally advanced or metastatic gastric cancer or gastroesophageal junction (GC/GEJ) adenocarcinoma patients with MET amplification who have failed at least two prior systemic treatments. ORPATHYS in combination with TAGRISSO is approved in China for patients with locally advanced or metastatic EGFR mutation-positive non-squamous NSCLC with MET amplification after disease progression on EGFR TKI therapy based on the SACHI Phase III trial. The combination was also granted a temporary authorization in Switzerland for the treatment of patients with locally advanced or metastatic EGFRm NSCLC and high levels of MET overexpression or amplification who progressed on prior treatment with TAGRISSO. This was based on results from the global SAVANNAH Phase II trial.

About TAGRISSO

TAGRISSO (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including the treatment of central nervous system metastases. TAGRISSO (40mg and 80mg QD oral tablets) has been used to treat more than one million patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO as a treatment for patients across multiple stages of EGFRm NSCLC.

TAGRISSO is approved as monotherapy in more than 120 countries including the US, EU, China and Japan. Approved indications include for first-line treatment of patients with locally advanced or metastatic EGFRm NSCLC, locally advanced or metastatic EGFR T790M mutation-positive NSCLC, adjuvant treatment of early-stage EGFRm NSCLC and locally advanced, unresectable NSCLC following platinum-based chemoradiation therapy. TAGRISSO is also approved in combination with chemotherapy in more than 80 countries, including the US, EU, China and Japan, for first-line treatment of patients with locally advanced or metastatic EGFRm NSCLC.

There is an extensive body of evidence supporting the use of TAGRISSO in EGFRm NSCLC, and it is the only targeted therapy shown to improve patient outcomes across all stages of the disease.

In late-stage disease, TAGRISSO demonstrated improved outcomes as monotherapy in the FLAURA Phase III trial and in combination with chemotherapy in the FLAURA2 Phase III trial. TAGRISSO is also being investigated in this setting in combination with DATROWAY (datopotamab deruxtecan or Dato-DXd) in the TROPION-Lung14 and TROPION-Lung15 Phase III trials.

TAGRISSO also showed improved outcomes in early-stage disease in the NeoADAURA and ADAURA Phase III trials and in locally advanced stages in the LAURA 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 early-stage adjuvant resectable setting in the ADAURA2 Phase III trial.

(Press release, Hutchison China MediTech, AUG 16, 2026, View Source [SID1234670162])