City of Hope Awarded $23.7 Million to Map Biomarkers Linked to Treatment Resistance in Patients With Common Lung Cancer
LOS ANGELES, June 17, 2025--(BUSINESS WIRE)--City of Hope®, one of the largest and most advanced cancer research and treatment organizations in the United States with its National Medical Center named a Top 5 "Best Hospital" in the nation for cancer care by U.S. News & World Report, has been awarded an up to $23.7 million contract from the Advanced Research Projects Agency for Health (ARPA-H) within the U.S. Department of Health and Human Services. The grant will help City of Hope create a bio map of tumor changes that cause immunotherapy resistance in advanced or metastatic non-small cell lung cancer (NSCLC).
City of Hope's Beckman Research Institute researchers will also test new biomarker-guided therapies in near real time NSCLC, which accounts for 87% of all lung cancer cases. By shaping physicians' management of the disease, the new findings offer promise for improving treatment success and extending the lives of the 200,000 patients diagnosed each year in the United States.
A six-year clinical trial, enrolling 535 patients, will provide the cornerstone for the City of Hope project, which is part of ARPA-H's Advanced Analysis for Precision Cancer Therapy (ADAPT) program. The up to $142 million initiative combines the latest technologies with the nation's top expertise in tumor biology to deliver customized cancer care that adapts to a patient's disease as it evolves.
"Changes in cancer may occur over time, creating resistance to immunotherapy and complicating oncologists' ability to identify the next best treatment approach," said Ravi Salgia, M.D., Ph.D., professor and chair of City of Hope's Department of Medical Oncology & Therapeutics Research, the Arthur & Rosalie Kaplan Chair in Medical Oncology, principal investigator with City of Hope's Aritro Nath, Ph.D., and Jyoti Malhotra, M.D., M.P.H. "Developing a biomap that detects mutations and other alterations early and predicts a patient's cancer trajectory will enable us to match treatments to evolving tumor biology and improve our patients' long-term survival."
Until now, cancer studies have focused on first-line therapy and lacked the flexibility to modify treatments as tumors grow. City of Hope will design its clinical trial to adjust treatment as resistance arises, with the goal of increasing progression-free survival by 50% in at least one patient group.
"Doctors have historically treated advanced non-small cell lung cancer with immune checkpoint inhibitors, sometimes combined with chemotherapy," explained Dr. Nath, City of Hope assistant professor with the Division of Molecular Pharmacology, Department of Medical Oncology & Therapeutics Research. "The main biomarker used to select immunotherapy, however, is not very reliable, with a patient response rate of less than 40%. We don't know why some patients become resistant to checkpoint inhibitors, and we have no good biomarkers to guide the choice of secondary treatments."
City of Hope intends to change that through meticulous monitoring and measurement of tumor changes in near real time.
Dr. Salgia and his colleagues will collect samples and detailed data at regular intervals from patients throughout the course of treatment. The researchers will monitor tumor trajectory and patients' response to treatment using state-of-the-art diagnostic techniques like liquid biopsies, single cell sequencing and radio imaging, relying on rapid turnaround times for comprehensive tumor measurements.
Instead of measuring a few data types at a single timepoint with limited predictive ability, the ADAPT program will take many measurements of diverse data over time and through multiple lines of treatments. The insights gleaned will help identify newly acquired resistant traits in tumors, predict the right therapies at each point in a patient's treatment and identify strategies that provide better long-term prognoses.
"We expect our collaboration with ADAPT will uncover predictive biomarkers that will enhance patient treatment and boost immunotherapy responses in non-small cell lung cancer," said Dr. Malhotra, associate professor with the Department of Medical Oncology & Therapeutics Research and interim division chief of Thoracic Medical Oncology, City of Hope, Los Angeles. "The information we gather will allow for informed adjustments in treatments and improve patient outcomes."
Equally important, the trial will leverage City of Hope's network of more than 35 clinical sites whose populations reflect the nation's lung cancer patients. The research team anticipates enrolling its first patients within 12 months.
With over 30 years of experience spearheading clinical trials and translational research, Dr. Salgia's leadership has been instrumental in uncovering key variants in lung cancer. He oversees more than 130 medical oncologists, including a nationwide team of 30 clinicians dedicated to lung cancer.
City of Hope investigators will fund the development, testing and matching of new biomarkers with therapeutic options that are now available or in a clinical trial. Algorithms and aggregate datasets developed under the program will be made publicly available, allowing scientists around the world to visualize trends and evaluate their implications and insights in near real time.
"We are incredibly excited to launch this ambitious project," said Dr. Salgia. "Our analysis of host and tumor biology will help clinicians counter the limits of current treatment choices and lead to better patient management strategies for advanced and metastatic non-small cell lung cancer."
About City of Hope
City of Hope's mission is to make hope a reality for all touched by cancer and diabetes. Founded in 1913, City of Hope has grown into one of the largest and most advanced cancer research and treatment organizations in the United States, and one of the leading research centers for diabetes and other life-threatening illnesses. City of Hope research has been the basis for numerous breakthrough cancer medicines, as well as human synthetic insulin and monoclonal antibodies. With an independent, National Cancer Institute-designated comprehensive cancer center that is ranked a Top 5 "Best Hospital" in the nation for cancer care by U.S. News & World Report at its core, City of Hope's uniquely integrated model spans cancer care, research and development, academics and training, and a broad philanthropy program that powers its work. City of Hope's growing national system includes its Los Angeles campus, a network of clinical care locations across Southern California, a new cancer center in Orange County, California, and cancer treatment centers and outpatient facilities in the Atlanta, Chicago and Phoenix areas. City of Hope's affiliated group of organizations includes Translational Genomics Research Institute and AccessHopeTM. For more information about City of Hope, follow us on Facebook, X, YouTube, Instagram and LinkedIn.
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Verastem Oncology Announces Nature Medicine Publication of the Results from the First-in-Human Phase 1 FRAME Study of Avutometinib in Combination with Defactinib in Solid Tumors, including Low-Grade Serious Ovarian Cancer
BOSTON--(BUSINESS WIRE)--Verastem Oncology (Nasdaq: VSTM), a biopharmaceutical company committed to advancing new medicines for patients with RAS/MAPK pathway-driven cancers, today announced that updated results from the Phase 1/2 FRAME study conducted by The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust were published online in Nature Medicine. The full manuscript, titled 'Defactinib with avutometinib in patients with solid tumors: the phase 1 FRAME trial,' was the first-in-human study to evaluate the safety, tolerability, and efficacy of avutometinib in combination with defactinib in patients with low-grade serous ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC), and other solid tumor types. 'The FRAME study was the early foundation for the recent FDA approval of avutometinib plus defactinib in KRAS-mutated recurrent low-grade serous ovarian cancer and we are pleased to see that the mature data set continues to show the safety and tolerability of this combination therapy,' said Dan Paterson, president and chief executive officer of Verastem Oncology. 'This supports our ongoing commitment to advancing our research into the combination for use in other solid tumors, including RAMP 205 in first-line metastatic pancreatic cancer.' The FRAME study enrolled patients, across dose escalation and dose expansion cohorts, with RAS-MAPK-driven solid tumors including LGSOC, NSCLC, colorectal, pancreatic and endometrial cancers. The updated data include an extended follow-up period and more detailed analyses from the FRAME study, featuring efficacy and safety data that demonstrated the novel combination of avutometinib and defactinib continues to be well-tolerated and shows encouraging responses in patients with LGSOC, consistent with previous findings. 'This was the first clinical study to show significant clinical activity of the combination of avutometinib, a RAF/MEK clamp, with defactinib, a FAK inhibitor. The FRAME study demonstrated an important potential advancement in the treatment of solid tumor diseases like low-grade serous ovarian cancer where seventy percent of these tumors are driven by the RAS/MAPK pathway and with thirty percent of these patients carrying a KRAS mutation,' said Professor Udai Banerji, co-Director of the Drug Development Unit, The Institute of Cancer Research and The Royal Marsden Hospital NHS Foundation Trust, London. 'We are pleased to have contributed to the development of avutometinib and defactinib. With FRAME's encouraging efficacy signal, the recommended Phase 2 dose was selected and the intermittent dosing schedule evaluated, which is the dose and schedule recently FDA approved in the U.S. and being used in the global confirmatory Phase 3 RAMP 301 trial.' In 26 patients with LGSOC who were evaluable for efficacy, the overall response rate (ORR) was 42.3% (11/26) and median progression-free survival (mPFS) was 20.1 months. In the 24 patients whose samples could be sequenced for KRAS mutations, ORR and mPFS were 58.3% (7/12) and 30.8 months in the 12 patients with KRAS mutations, and 33.3% (4/12) and 8.9 months in the 12 patients without KRAS mutations. In 11 patients who had previously received a MEK inhibitor, the ORR was 27.3% (3/11). Additionally, in two patients with LGSOC who had brain metastases prior to enrolling, MRI imaging at 30 months post-treatment with the combination showed the metastases had shrunk in both patients. In 27 patients with LGSOC who were evaluable for safety, only one (4%) discontinued treatment due to Grade 3 skin toxicity. The five most common adverse events (AEs) (all grades, grade ≥3) were: rash (90%, 8%), elevated blood levels of creatine phosphokinase (56%, 9%), AST elevation (43%, 1%), hyperbilirubinemia (38%, 2%), and diarrhea (38%, 1%). The tolerability profile of avutometinib plus defactinib was comparable to the tolerability of each agent as monotherapy. About the Phase 1/2 FRAME Study The FRAME study is an open-label, investigator-initiated study that is designed to assess safety, dose response, and preliminary efficacy of the VS-6766/defactinib combination in patients with KRAS mutant solid tumors, including low-grade serous ovarian cancer (LGSOC), non-small cell lung cancer (NSCLC) and colorectal cancer (CRC). The FRAME study is being led by Professor Udai Banerji, MBBS, MD, DNB, PhD, FRCP, Deputy Director of the Drug Development Unit at The Institute of Cancer Research, London, and The Royal Marsden NHS Foundation Trust, and is being conducted in the United Kingdom. In this study, VS-6766 was administered using a twice-weekly dose escalation schedule and was administered three out of every four weeks. Defactinib was administered using a twice-daily dose escalation schedule, also three out of every four weeks. Dose levels were assessed in three cohorts: cohort 1 (avutometinib 3.2mg, defactinib 200mg); cohort 2a (avutometinib 4mg, defactinib 200mg); and cohort 2b (avutometinib 3.2mg, defactinib 400mg). The recommended Phase 2 dose was determined to be cohort 1 (avutometinib 3.2mg, defactinib 200mg). About Low-Grade Serous Ovarian Cancer (LGSOC) LGSOC is a rare ovarian cancer that is insidious and persistent. LGSOC is distinct and different from high-grade serous ovarian cancer (HGSOC) and requires different treatment. LGSOC is highly recurrent and less sensitive to chemotherapy compared to HGSOC. Approximately 6,000-8,000 women in the U.S. and 80,000 worldwide are living with this disease. LGSOC affects younger women with bimodal peaks of diagnosis at ages between 20-30 and 50-60 and has a median survival of approximately ten years. Approximately 70 percent of LGSOC shows RAS pathway-associated mutations, and 30 percent of people with LGSOC have a KRAS mutation. The majority of patients report a negative impact of LGSOC on their mental and physical health, fertility, and long-term quality of life. About AVMAPKI and FAKZYNJA Combination Therapy AVMAPKI (avutometinib) inhibits MEK kinase activity while also blocking the compensatory reactivation of MEK by upstream RAF. RAF and MEK proteins are regulators of the RAS/RAF/MEK/ERK (MAPK) pathway. Blocking RAF and/or MEK activates FAK, a key mediator of drug resistance. FAKZYNJA (defactinib) is a FAK inhibitor and together, the avutometinib and defactinib combination was designed to provide a more complete blockade of the signaling that drives the growth and drug resistance of RAS/MAPK pathway-dependent tumors. The U.S. Food and Drug Administration (FDA) approved AVMAPKI™ FAKZYNJA™ CO-PACK (avutometinib capsules; defactinib tablets) for the treatment of adult patients with KRAS-mutated recurrent LGSOC who have received prior systemic therapy on May 8, 2025. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Verastem is conducting RAMP 301 (GOG-3097/ENGOT-ov81/GTG-UK) (NCT06072781), an international Phase 3 confirmatory trial evaluating the combination of avutometinib and defactinib versus standard chemotherapy or hormonal therapy for the treatment of recurrent low-grade serous ovarian cancer (LGSOC) with and without a KRAS mutation. Verastem is also evaluating avutometinib in combination with defactinib and other agents as a potential treatment for patients with advanced pancreatic cancer (RAMP 205; NCT05669482) and advanced KRAS G12C mutant non-small cell lung cancer (RAMP 203; NCT05074810). Avutometinib and defactinib are not approved by the FDA or any other regulatory authority, either in combination or with other therapies, for any of these investigative uses. Neither avutometinib nor defactinib are approved by the FDA or any other regulatory authority on a stand-alone basis for any use. AVMAPKI FAKZYNJA CO-PACK U.S. Indication Indication AVMAPKI FAKZYNJA CO-PACK is indicated for the treatment of adult patients with KRAS -mutated recurrent low-grade serous ovarian cancer (LGSOC) who have received prior systemic therapy. This indication is approved under accelerated approval based on tumor response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial. Important Safety Information Warnings and Precautions Ocular Toxicities: Ocular toxicities, including visual impairment and vitreoretinal disorders, occurred. Perform comprehensive ophthalmic evaluation at baseline, prior to cycle 2, every three cycles thereafter, and as clinically indicated. Withhold AVMAPKI FAKZYNJA CO-PACK for ocular toxicities until improvement at the same or reduced dose. Permanently discontinue AVMAPKI FAKZYNJA CO-PACK for any grade 4 toxicity. Serious Skin Toxicities: Skin toxicities, including photosensitivity and severe cutaneous adverse reactions (SCARSs) occurred. Adhere to concomitant medications. Monitor for skin toxicities and interrupt, reduce or permanently discontinue AVMAPKI FAKZYNJA CO-PACK based on severity, tolerability and duration. Hepatotoxicity: Monitor liver function tests prior to each cycle, on day 15 of the first 4 cycles, and as clinically indicated. Withhold, reduce or discontinue AVMAPKI FAKZYNJA CO-PACK based on severity and persistence of abnormality. Rhabdomyolysis: Monitor creatine phosphokinase prior to the start of each cycle, on day 15 of the first four cycles, and as clinically indicated. If increased CPK occurs, evaluate patients for rhabdomyolysis or other causes. Withhold, reduce or permanently discontinue AVMAPKI FAKZYNJA CO-PACK based on severity and duration of the adverse reaction. Embryo-Fetal Toxicity: AVMAPKI FAKZYNJA CO-PACK can cause fetal harm. Advise patients of the potential risk to a fetus and to use effective contraception. Adverse Reactions The most common (≥ 25%) adverse reactions, including laboratory abnormalities, were increased creatine phosphokinase, nausea, fatigue, increased aspartate aminotransferase, rash, diarrhea, musculoskeletal pain, edema, decreased hemoglobin, increased alanine aminotransferase, vomiting, increased blood bilirubin, increased triglycerides, decreased lymphocyte count, abdominal pain, dyspepsia, dermatitis acneiform, vitreoretinal disorders, increased alkaline phosphatase, stomatitis, pruritus, visual impairment, decreased platelet count, constipation, dry skin, dyspnea, cough, urinary tract infection, and decreased neutrophil count. Drug Interactions Strong and moderate CYP3A4 inhibitors: Avoid concomitant use with AVMAPKI FAKZYNJA CO-PACK. Strong and moderate CYP3A4 inducers: Avoid concomitant use with AVMAPKI FAKZYNJA CO-PACK. Warfarin: Avoid concomitant use of AVMAPKI FAKZYNJA CO-PACK with warfarin and use an alternative to warfarin. Gastric acid reducing agents: Avoid concomitant use of AVMAPKI FAKZYNJA CO-PACK with proton pump inhibitors (PPIs) or H2 receptor antagonists. If use of an acid-reducing agent cannot be avoided, administer FAKZYNJA 2 hours before or 2 hours after the administration of a locally acting antacid. Use in Specific Populations Lactation: Advise not to breastfeed. Fertility: May impair fertility in males and females. Click here for full Prescribing Information. About Verastem Oncology Verastem Oncology (Nasdaq: VSTM) is a biopharmaceutical company committed to developing and commercializing new medicines to improve the lives of patients diagnosed with RAS/MAPK pathway-driven cancers. Verastem markets AVMAPKI™ FAKZYNJA™ CO-PACK in the U.S. Our pipeline is focused on novel small molecule drugs that inhibit critical signaling pathways in cancer that promote cancer cell survival and tumor growth, including RAF/MEK inhibition, FAK inhibition, and KRAS G12D inhibition. For more information, please visit and follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933 and Section 21E of the Securities Exchange Act of 1934. All statements other than historical statements of fact regarding Verastem's expectations, beliefs, goals, plans or prospects including, without limitation, statements about AVMAPKI FAKZYNJA CO-PACK's potential to benefit adult patients living with KRAS-mutated recurrent low-grade serous ovarian cancer in the United States, AVMAPKI FAKZYNJA CO-PACK's potential to be a transformational medicine, and AVMAPKI FAKZYNJA CO-PACK's potential to be an important treatment option for patients with KRAS-mutated recurrent low-grade serous ovarian cancer should be considered forward-looking statements. The words "anticipate," "believe," "estimate," "expect," "intend," "may," "plan," "predict," "project," "target," "potential," "would," "could," "should," "continue," 'can,' 'promising' and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Each forward-looking statement is subject to risks and uncertainties that could cause actual results to differ materially from those expressed or implied in such statement. Actual results and future plans may differ materially from those indicated by these forward-looking statements as a result of various important risks, uncertainties and other factors, including, without limitation, risks and uncertainties relating to: the launch AVMAPKI FAKZYNJA CO-PACK in the United States including having the product available in the market following launch and thereafter; the adoption of the product by health care professionals; establishing favorable pricing for the product and securing reimbursement coverage from third-party payors, including government agencies, for the product; establishing the product as the standard of care for KRAS-mutant recurrent LGSOC; actions or advice of regulatory agencies and our ability to obtain and maintain regulatory approval for our product; the market opportunities for AVMAPKI FAKZYNJA CO-PACK are based on internal and third-party estimates that may prove to be incorrect; that there may be competitive developments affecting our product candidates; that data may not be available when expected; that our product may cause adverse safety events or unexpected concerns may arise from additional data or analysis, or result in unmanageable safety profiles as compared to its level of efficacy; that we may be unable to successfully validate, develop and obtain regulatory approval for companion diagnostic tests for our product that require or would commercially benefit from such tests, or experience significant delays in doing so; that our product may experience manufacturing or supply interruptions or failures; that we face substantial competition, which may result in others developing or commercializing products before or more successfully than we do which could result in reduced market share or market potential for our product candidates; the discovery and development of novel drug candidates and delivery approaches and successful demonstration of the efficacy and safety of our product candidates; the pre-clinical and clinical results for our product candidates; that we may not have sufficient cash to fund our contemplated operations, including certain of our product commercialization and development programs; that we may not attract and retain high quality personnel; that we may not be able to expand the approved indication for AVMAPKI FAKZYNJA CO-PACK; that we may not be able to successfully launch, market and sell AVMAPKI FAKZYNJA CO-PACK in the United States and realize all or a substantial portion of the potential market opportunity; that we may not be able to successfully launch, market and sell approved products globally; that there may be delays, interruptions or failures in the manufacture and supply of our product candidates or marketed products; that we successfully obtain, maintain and protect intellectual property on our development and marketed products; that we are able to manage growth and operating expenses through disciplined investment in operations and able to achieve a self-sustainable financial profile in the future and avoid or successfully manage unexpected expenditures; that we are able to maintain strategic business collaborations; the dependence on third parties for the development and commercialization of certain products; the risks and uncertainties related to the recent change in the U.S. presidential administration, including regulatory and policy changes that may adversely affect our business; the risk of future government investigations and substantial changes in governmental polices, regulations, funding and enforcement; as well as those risks and uncertainties more fully discussed in the 'Risk Factors' filed with Verastem's 2024 Annual Report on Form 10-K filed with the Securities and Exchange Commission (SEC) on March 20 th, 2025, as may be updated from time to time in Verastem's subsequent Quarterly Reports on Form 10-Q, and in other filings that Verastem makes with the SEC.
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HUTCHMED Announces China Approval for ORPATHYS® in Combination with TAGRISSO® for the Treatment of Lung Cancer Patients with MET Amplification After Progression on First-Line EGFR Inhibitor Therapy
— Approval based on Phase III SACHI Trial results which showed a 66% reduced risk of progression or death as compared to platinum-based chemotherapy — — The only all-oral combination treatment option for these patients — — Consistent benefit regardless of first-line EGFR inhibitor therapy — HONG KONG, SHANGHAI and FLORHAM PARK, N.J., June 30, 2025 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited ('HUTCHMED') (Nasdaq/AIM:HCM; HKEX:13) today announces that the New Drug Application ('NDA') for the combination of ORPATHYS® (savolitinib) and TAGRISSO® (osimertinib) has been granted approval by the China National Medical Products Administration ('NMPA') for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor ('EGFR') mutation-positive non-squamous non-small cell lung cancer ('NSCLC') with MET amplification after disease progression on EGFR tyrosine kinase inhibitor ('TKI') therapy. ORPATHYS® is an oral, potent and highly selective MET TKI. TAGRISSO® is a third-generation, irreversible EGFR TKI. This approval also triggers a US$11 million milestone payment from AstraZeneca, which markets both ORPATHYS® and TAGRISSO® in China. ORPATHYS® was the first selective MET inhibitor approved in China, indicated for adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alteration. This new approval by the NMPA was based on data from the SACHI Phase III trial of the ORPATHYS® and TAGRISSO® combination (NCT05015608), having met the pre-defined primary endpoint of progression-free survival ('PFS') in a pre-planned interim analysis. Primary results were presented at the American Society of Clinical Oncology ('ASCO') Annual Meeting in June 2025. In 2024 the NMPA designated the combination as a Breakthrough Therapy, and in 2025 it granted the NDA Priority Review. Professor Shun Lu, Chief of the Shanghai Lung Cancer Center at Shanghai Chest Hospital, School of Medicine, Shanghai Jiaotong University, and Principal Investigator of the SACHI trial, said, 'The approval of the ORPATHYS® and TAGRISSO® combination is a significant milestone in addressing the complex challenges of lung cancer treatment in China, where the EGFR mutation is common amongst NSCLC patients. For patients who develop MET amplification after progressing on EGFR inhibitors, the combination offers a continued all-oral, chemotherapy-free approach to tackle a critical resistance mechanism. As a researcher and clinician, I am excited about the opportunity to offer this targeted therapy to patients, improving their treatment outcomes and quality of life through innovative research.' 'The NMPA approval marks an important step forward in our mission to address MET-driven progression following first-line EGFR-inhibitor therapy in NSCLC patients.' said Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED. 'Our collaboration with AstraZeneca, built on a shared vision to transform oncology care, has been crucial in reaching this achievement. We are committed to advancing this partnership, continuing our research into further treatment settings, and bringing this innovative combination to patients in China and beyond.' Ms Mary Guan, General Manager of AstraZeneca China Oncology Business, said: 'This milestone marks the third indication of ORPATHYS® approved in China, bringing a new treatment option to lung cancer patients who develop MET amplification after progressing on EGFR inhibitor therapy. Through our partnership with HUTCHMED, we are committed to expanding the reach of the ORPATHYS® and TAGRISSO® combination to address progression on first-line therapy and help even more patients with this form of lung cancer.' In the intention to treat (ITT) population of the SACHI trial, the ORPATHYS® and TAGRISSO® combination reduced the risk of disease progression by 66% with a median PFS of 8.2 months, compared to 4.5 months for chemotherapy, as assessed by investigators. The independent review committee (IRC) also reported a 60% risk reduction in disease progression, with a median PFS of 7.2 months versus 4.2 months, respectively. The safety profile of the ORPATHYS® and TAGRISSO® combination was tolerable and no new safety signals were observed. Treatment-emergent adverse events of Grade 3 or above occurred in 57% of patients in both the ORPATHYS® plus TAGRISSO® group and the chemotherapy group, suggesting a favorable safety profile. About NSCLC and MET aberrations Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.2 The majority of NSCLC patients (approximately 75%) are diagnosed with advanced disease, and approximately 10-15% of NSCLC patients in the US and Europe and 30-40% of patients in Asia have EGFR-mutated ('EGFRm') NSCLC.3,4,5,6 MET is a tyrosine kinase receptor that has an essential role in normal cell development. MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is one of the mechanisms of acquired resistance to EGFR TKI for metastatic EGFRm NSCLC.7,8 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 and is marketed by AstraZeneca 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. It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers as a single treatment and in combination with other medicines. About TAGRISSO® TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. TAGRISSO® (40mg and 80mg once-daily oral tablets) has been used to treat nearly 800,000 patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO® as a treatment for patients across multiple stages of EGFRm NSCLC. There is an extensive body of evidence supporting the use of TAGRISSO® as standard of care in EGFRm NSCLC. TAGRISSO® improved patient outcomes in early-stage disease in the ADAURA Phase III trial, locally advanced disease in the LAURA Phase III trial, late-stage disease in the FLAURA Phase III trial, and with chemotherapy in the FLAURA2 Phase III trial. About ORPATHYS® and TAGRISSO® Combination Development in EGFR-mutated NSCLC Among patients who experience disease progression following treatment with a third-generation EGFR TKI, approximately 15-50% present with MET aberration, depending on the sample type, detection method and assay cut-off used. TAGRISSO® is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. Treatment with ORPATHYS® in combination with TAGRISSO® has been studied extensively in these patients in the TATTON (NCT02143466) and SAVANNAH (NCT03778229) studies. The encouraging results led to the initiation of several Phase III trials in this setting including the SACHI trial in China (NCT05015608) and the global SAFFRON trial (NCT05261399), as well as the SANOVO trial in China (NCT05009836). This combination represents a promising chemotherapy-free oral treatment strategy to address mechanisms of resistance in this advanced setting. Positive data from the SACHI randomized Phase III trial led to the filing of a second NDA in China. Strong data from the SAVANNAH single-arm Phase II study was recently presented at the European Lung Cancer Congress (ELCC) in March 2025 demonstrated high, clinically meaningful and durable objective response rate (ORR), with consistent safety results. The SAFFRON randomized Phase III trial is progressing. Following AstraZeneca's consultation with the US Food and Drug Administration ('FDA'), we look forward to completing the SAFFRON trial as soon as possible to support potential US and other global registration filings. The SACHI China Phase III trial met the primary endpoint of PFS during its interim analysis towards the end of 2024 and a NDA was accepted and granted Breakthrough Therapy Designation and Priority Review status in China in December 2024. SACHI evaluated the combination of ORPATHYS® and TAGRISSO® for the treatment of patients with EGFRm, MET-amplified locally advanced or metastatic NSCLC after progression on EGFR TKI compared to platinum-based doublet chemotherapy. Results were presented at the ASCO Annual Meeting in June 2025. In 2023, ORPATHYS® and TAGRISSO® received Fast Track Designation from the US FDA in this setting. The global SAFFRON Phase III trial is currently ongoing to assess the ORPATHYS® plus TAGRISSO® combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following progression on treatment with TAGRISSO®. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH. About HUTCHMED HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. Since inception it has focused on bringing drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved around the world including in the US, Europe and Japan. For more information, please visit: or follow us on announcement contains forward-looking statements within the meaning of the 'safe harbor' provisions of the US Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED's current expectations regarding future events, including its expectations regarding the therapeutic potential of ORPATHYS®, the further clinical development for ORPATHYS®, its expectations as to whether any studies on ORPATHYS® would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates and the timing and availability of subjects meeting a study's inclusion and exclusion criteria; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of ORPATHYS®, including as a combination therapy, to meet the primary or secondary endpoint of a study, to obtain regulatory approval in other jurisdictions and to gain commercial acceptance after obtaining regulatory approval; the potential market of ORPATHYS® for a targeted indication; and HUTCHMED and/or its partner's ability to fund, implement and complete its further clinical development and commercialization plans for ORPATHYS®, and the timing of these events. In addition, as certain studies rely on the use of other drug products such as TAGRISSO® as combination therapeutics with ORPATHYS®, such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED's filings with the US Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this announcement, whether as a result of new information, future events or circumstances or announcement contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018). CONTACTS Investor Enquiries +852 2121 8200 / ir@ Media Enquiries FTI Consulting – +44 20 3727 1030 / HUTCHMED@ Ben Atwell / Alex Shaw +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) Brunswick – Zhou Yi +852 9783 6894 (Mobile) / HUTCHMED@ Panmure Liberum Nominated Advisor and Joint Broker Atholl Tweedie / Emma Earl / Rupert Dearden +44 20 7886 2500 Cavendish Joint Broker Geoff Nash / Nigel Birks +44 20 7220 0500 ________________________ 1 World Health Organization. International Agency for Research on Cancer. All cancers fact sheet. Available at: Accessed November 2022. 2 American Cancer Society. What is Lung Cancer? Available at: Accessed November 2022. 3 Knight SB, et al. Progress and prospects of early detection in lung cancer. Open Biol. 2017;7(9): 170070. 4 Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27. 5 Zhang Y, 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). 6 Szumera-Ciećkiewicz A, et al. EGFR Mutation Testing on Cytological and Histological Samples in 11. Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol. 2013:6;2800-12. 7 Uchikawa E, et al. Structural basis of the activation of c-MET receptor. Nat Commun. 2021;12(4074). 8 Wang Q, et al. MET inhibitors for targeted therapy of EGFR TKI-resistant lung cancer. Journal of Hematology & Oncology. 2019;63.
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HUTCHMED Announces China Approval for ORPATHYS® in Combination with TAGRISSO® for the Treatment of Lung Cancer Patients with MET Amplification After Progression on First-Line EGFR Inhibitor Therapy
— Approval based on Phase III SACHI Trial results which showed a 66% reduced risk of progression or death as compared to platinum-based chemotherapy — — The only all-oral combination treatment option for these patients — — Consistent benefit regardless of first-line EGFR inhibitor therapy — HONG KONG, SHANGHAI and FLORHAM PARK, N.J., June 30, 2025 (GLOBE NEWSWIRE) — HUTCHMED (China) Limited ('HUTCHMED') (Nasdaq/AIM:HCM; HKEX:13) today announces that the New Drug Application ('NDA') for the combination of ORPATHYS® (savolitinib) and TAGRISSO® (osimertinib) has been granted approval by the China National Medical Products Administration ('NMPA') for the treatment of patients with locally advanced or metastatic epidermal growth factor receptor ('EGFR') mutation-positive non-squamous non-small cell lung cancer ('NSCLC') with MET amplification after disease progression on EGFR tyrosine kinase inhibitor ('TKI') therapy. ORPATHYS® is an oral, potent and highly selective MET TKI. TAGRISSO® is a third-generation, irreversible EGFR TKI. This approval also triggers a US$11 million milestone payment from AstraZeneca, which markets both ORPATHYS® and TAGRISSO® in China. ORPATHYS® was the first selective MET inhibitor approved in China, indicated for adult patients with locally advanced or metastatic NSCLC with MET exon 14 skipping alteration. This new approval by the NMPA was based on data from the SACHI Phase III trial of the ORPATHYS® and TAGRISSO® combination (NCT05015608), having met the pre-defined primary endpoint of progression-free survival ('PFS') in a pre-planned interim analysis. Primary results were presented at the American Society of Clinical Oncology ('ASCO') Annual Meeting in June 2025. In 2024 the NMPA designated the combination as a Breakthrough Therapy, and in 2025 it granted the NDA Priority Review. Professor Shun Lu, Chief of the Shanghai Lung Cancer Center at Shanghai Chest Hospital, School of Medicine, Shanghai Jiaotong University, and Principal Investigator of the SACHI trial, said, 'The approval of the ORPATHYS® and TAGRISSO® combination is a significant milestone in addressing the complex challenges of lung cancer treatment in China, where the EGFR mutation is common amongst NSCLC patients. For patients who develop MET amplification after progressing on EGFR inhibitors, the combination offers a continued all-oral, chemotherapy-free approach to tackle a critical resistance mechanism. As a researcher and clinician, I am excited about the opportunity to offer this targeted therapy to patients, improving their treatment outcomes and quality of life through innovative research.' 'The NMPA approval marks an important step forward in our mission to address MET-driven progression following first-line EGFR-inhibitor therapy in NSCLC patients.' said Dr Weiguo Su, Chief Executive Officer and Chief Scientific Officer of HUTCHMED. 'Our collaboration with AstraZeneca, built on a shared vision to transform oncology care, has been crucial in reaching this achievement. We are committed to advancing this partnership, continuing our research into further treatment settings, and bringing this innovative combination to patients in China and beyond.' Ms Mary Guan, General Manager of AstraZeneca China Oncology Business, said: 'This milestone marks the third indication of ORPATHYS® approved in China, bringing a new treatment option to lung cancer patients who develop MET amplification after progressing on EGFR inhibitor therapy. Through our partnership with HUTCHMED, we are committed to expanding the reach of the ORPATHYS® and TAGRISSO® combination to address progression on first-line therapy and help even more patients with this form of lung cancer.' In the intention to treat (ITT) population of the SACHI trial, the ORPATHYS® and TAGRISSO® combination reduced the risk of disease progression by 66% with a median PFS of 8.2 months, compared to 4.5 months for chemotherapy, as assessed by investigators. The independent review committee (IRC) also reported a 60% risk reduction in disease progression, with a median PFS of 7.2 months versus 4.2 months, respectively. The safety profile of the ORPATHYS® and TAGRISSO® combination was tolerable and no new safety signals were observed. Treatment-emergent adverse events of Grade 3 or above occurred in 57% of patients in both the ORPATHYS® plus TAGRISSO® group and the chemotherapy group, suggesting a favorable safety profile. About NSCLC and MET aberrations Lung cancer is the leading cause of cancer death, accounting for about one-fifth of all cancer deaths.1 Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.2 The majority of NSCLC patients (approximately 75%) are diagnosed with advanced disease, and approximately 10-15% of NSCLC patients in the US and Europe and 30-40% of patients in Asia have EGFR-mutated ('EGFRm') NSCLC.3,4,5,6 MET is a tyrosine kinase receptor that has an essential role in normal cell development. MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is one of the mechanisms of acquired resistance to EGFR TKI for metastatic EGFRm NSCLC.7,8 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 and is marketed by AstraZeneca 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. It is currently under clinical development for multiple tumor types, including lung, kidney, and gastric cancers as a single treatment and in combination with other medicines. About TAGRISSO® TAGRISSO® (osimertinib) is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system (CNS) metastases. TAGRISSO® (40mg and 80mg once-daily oral tablets) has been used to treat nearly 800,000 patients across its indications worldwide and AstraZeneca continues to explore TAGRISSO® as a treatment for patients across multiple stages of EGFRm NSCLC. There is an extensive body of evidence supporting the use of TAGRISSO® as standard of care in EGFRm NSCLC. TAGRISSO® improved patient outcomes in early-stage disease in the ADAURA Phase III trial, locally advanced disease in the LAURA Phase III trial, late-stage disease in the FLAURA Phase III trial, and with chemotherapy in the FLAURA2 Phase III trial. About ORPATHYS® and TAGRISSO® Combination Development in EGFR-mutated NSCLC Among patients who experience disease progression following treatment with a third-generation EGFR TKI, approximately 15-50% present with MET aberration, depending on the sample type, detection method and assay cut-off used. TAGRISSO® is a third-generation, irreversible EGFR-TKI with proven clinical activity in NSCLC, including against central nervous system metastases. Treatment with ORPATHYS® in combination with TAGRISSO® has been studied extensively in these patients in the TATTON (NCT02143466) and SAVANNAH (NCT03778229) studies. The encouraging results led to the initiation of several Phase III trials in this setting including the SACHI trial in China (NCT05015608) and the global SAFFRON trial (NCT05261399), as well as the SANOVO trial in China (NCT05009836). This combination represents a promising chemotherapy-free oral treatment strategy to address mechanisms of resistance in this advanced setting. Positive data from the SACHI randomized Phase III trial led to the filing of a second NDA in China. Strong data from the SAVANNAH single-arm Phase II study was recently presented at the European Lung Cancer Congress (ELCC) in March 2025 demonstrated high, clinically meaningful and durable objective response rate (ORR), with consistent safety results. The SAFFRON randomized Phase III trial is progressing. Following AstraZeneca's consultation with the US Food and Drug Administration ('FDA'), we look forward to completing the SAFFRON trial as soon as possible to support potential US and other global registration filings. SACHI: The SACHI China Phase III trial met the primary endpoint of PFS during its interim analysis towards the end of 2024 and a NDA was accepted and granted Breakthrough Therapy Designation and Priority Review status in China in December 2024. SACHI evaluated the combination of ORPATHYS® and TAGRISSO® for the treatment of patients with EGFRm, MET-amplified locally advanced or metastatic NSCLC after progression on EGFR TKI compared to platinum-based doublet chemotherapy. Results were presented at the ASCO Annual Meeting in June 2025. SAFFRON: In 2023, ORPATHYS® and TAGRISSO® received Fast Track Designation from the US FDA in this setting. The global SAFFRON Phase III trial is currently ongoing to assess the ORPATHYS® plus TAGRISSO® combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following progression on treatment with TAGRISSO®. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH. About HUTCHMED HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery and global development and commercialization of targeted therapies and immunotherapies for the treatment of cancer and immunological diseases. Since inception it has focused on bringing drug candidates from in-house discovery to patients around the world, with its first three medicines marketed in China, the first of which is also approved around the world including in the US, Europe and Japan. For more information, please visit: or follow us on LinkedIn. Forward-Looking Statements This announcement contains forward-looking statements within the meaning of the 'safe harbor' provisions of the US Private Securities Litigation Reform Act of 1995. These forward-looking statements reflect HUTCHMED's current expectations regarding future events, including its expectations regarding the therapeutic potential of ORPATHYS ® , the further clinical development for ORPATHYS ® , its expectations as to whether any studies on ORPATHYS ® would meet their primary or secondary endpoints, and its expectations as to the timing of the completion and the release of results from such studies. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding enrollment rates and the timing and availability of subjects meeting a study's inclusion and exclusion criteria; changes to clinical protocols or regulatory requirements; unexpected adverse events or safety issues; the ability of ORPATHYS ® , including as a combination therapy, to meet the primary or secondary endpoint of a study, to obtain regulatory approval in other jurisdictions and to gain commercial acceptance after obtaining regulatory approval; the potential market of ORPATHYS ® for a targeted indication; and HUTCHMED and/or its partner's ability to fund, implement and complete its further clinical development and commercialization plans for ORPATHYS ® , and the timing of these events. In addition, as certain studies rely on the use of other drug products such as TAGRISSO ® as combination therapeutics with ORPATHYS ® , such risks and uncertainties include assumptions regarding the safety, efficacy, supply and continued regulatory approval of these therapeutics. Existing and prospective investors are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. For further discussion of these and other risks, see HUTCHMED's filings with the US Securities and Exchange Commission, The Stock Exchange of Hong Kong Limited and on AIM. HUTCHMED undertakes no obligation to update or revise the information contained in this announcement, whether as a result of new information, future events or circumstances or otherwise. Medical Information This announcement contains information about products that may not be available in all countries, or may be available under different trademarks, for different indications, in different dosages, or in different strengths. Nothing contained herein should be considered a solicitation, promotion or advertisement for any prescription drugs including the ones under development. Inside Information This announcement contains inside information for the purposes of Article 7 of Regulation (EU) No 596/2014 (as it forms part of retained EU law as defined in the European Union (Withdrawal) Act 2018). CONTACTS Investor Enquiries +852 2121 8200 / [email protected] Media Enquiries FTI Consulting – +44 20 3727 1030 / [email protected] Ben Atwell / Alex Shaw +44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile) Brunswick – Zhou Yi +852 9783 6894 (Mobile) / [email protected] Panmure Liberum Nominated Advisor and Joint Broker Atholl Tweedie / Emma Earl / Rupert Dearden +44 20 7886 2500 Cavendish Joint Broker Geoff Nash / Nigel Birks +44 20 7220 0500 ________________________ 1 World Health Organization. International Agency for Research on Cancer. All cancers fact sheet. Available at: Accessed November 2022. 2 American Cancer Society. What is Lung Cancer? Available at: Accessed November 2022. 3 Knight SB, et al. Progress and prospects of early detection in lung cancer. Open Biol. 2017;7(9): 170070. 4 Keedy VL, et al. American Society of Clinical Oncology Provisional Clinical Opinion: Epidermal Growth Factor Receptor (EGFR) Mutation Testing for Patients with Advanced Non-Small-Cell Lung Cancer Considering First-Line EGFR Tyrosine Kinase Inhibitor Therapy. J Clin Oncol. 2011:29;2121-27. 5 Zhang Y, 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). 6 Szumera-Ciećkiewicz A, et al . EGFR Mutation Testing on Cytological and Histological Samples in 11. Non-Small Cell Lung Cancer: a Polish, Single Institution Study and Systematic Review of European Incidence. Int J Clin Exp Pathol . 2013:6;2800-12. 7 Uchikawa E, et al . Structural basis of the activation of c-MET receptor. Nat Commun. 2021;12(4074). 8 Wang Q, et al. MET inhibitors for targeted therapy of EGFR TKI-resistant lung cancer . Journal of Hematology & Oncology. 2019;63. 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