A Phase II Clinical Study on Precision Treatment of Rare Tumours in China Guided by Patient-Derived Tumor Organoids (PDO) and Next-Generation Sequencing (NGS)

The objective of this Phase II, open-label, multicenter, non-randomised controlled clinical trial is to guide precision treatment for patients with rare tumours based on Patient-Derived Organoids/Next-Generation Sequencing drug screening.

Start Date01 Jan 2025

Sponsor / Collaborator

Peking University Shenzhen Hospital

NCT06563999

/ RecruitingPhase 2IIT

Neoadjuvant Umbrella Trial Directed by Next Generation Sequencing for Patients With Unresectable Stage III NSCLC Harboring Rare Mutations (Without EGFR Sensitizing Mutations)

This umbrella trial directed by next generation sequencing (NGS) includes patients with treatment-naive unresectable stage III non-small-cell lung cancer (NSCLC). The aim of the umbrella study is to evaluate the efficacy of induction NGS-directed targeted therapies followed by surgery for stage III NSCLC patients whose tumor harbors a rare mutation.

Start Date01 Nov 2024

Sponsor / Collaborator

Sun Yat-Sen University

NCT06348355

/ CompletedPhase 1

A Phase I, Open-label, Positron-Emission Tomography Study to Determine Brain Exposure of [11C]Savolitinib in Healthy Volunteers

The purpose of this study is to measure brain exposure of [11C]savolitinib in healthy volunteers.
This study will determine brain exposure of [11C]savolitinib in up to 8 healthy volunteers under physiological conditions, ie, when the BBB is intact. The study design allows up to 3 site visits. Two PET examinations will be performed for each healthy volunteer. The first PET examination will use IV administration of [11C]savolitinib. The second PET examination using [11C]savolitinib will occur after a single oral dose of 300 mg of savolitinib. PET image analysis will include kinetic compartment modelling using arterial input function, and will generate a set of brain exposure parameters (eg, maximum %ID, maximum [11C]savolitinib concentration in brain, partition coefficients between brain and plasma).

Start Date12 Apr 2024

Sponsor / Collaborator

AstraZeneca PLC

100 Clinical Results associated with Savolitinib

100 Translational Medicine associated with Savolitinib

100 Patents (Medical) associated with Savolitinib

197

Literatures (Medical) associated with Savolitinib

01 Dec 2025·Journal of Gastrointestinal Cancer

A Phase 2 study of Savolitinib in Patients with MET Amplified Metastatic Colorectal Cancer

Article

Author: Lowe, Melissa ; Niedzwiecki, Donna ; Kortmansky, Jeremy ; Moyer, Ashley ; Bolch, Emily ; Jia, Jingquan ; Cho, May ; Kalyan, Aparna ; Strickler, John H ; Lenz, Heinz-Josef

PURPOSE:

MET amplification (amp) is a driver of acquired resistance to epidermal growth factor receptor (EGFR) antibodies in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC). Savolitinib is an oral small molecule tyrosine kinase inhibitor that has demonstrated anti-tumor activity in MET-driven advanced solid tumors. We report the results of a phase 2 study of savolitinib in patients with mCRC with MET amp detected by circulating cell free (cf)DNA.

METHODS:

Patients with chemotherapy refractory mCRC and MET amp detected by cfDNA were treated with savolitinib until unacceptable toxicity or disease progression. The primary endpoint was objective response rate. Secondary endpoints were clinical activity and safety.

RESULTS:

Five patients were enrolled and treated. Best overall response was stable disease (SD) in two patients, progressive disease (PD) in two patients, and one patient unevaluable for response. The majority of treatment-emergent adverse events (TEAEs) were grade 1 or 2. The most common TEAEs included fatigue (n = 3) and nausea (n = 3). There were no grade 4 or 5 TEAEs.

CONCLUSION:

Savolitinib was well tolerated; however, in this small group of biomarker-selected patients, we observed no evidence of anti-tumor activity.

TRIAL REGISTRATION:

Clinicaltrials.gov Identifier: NCT03592641. Registered on July 17, 2018.

01 Dec 2024·Lancet Respiratory Medicine

Savolitinib in NSCLC: progress in the MET exon 14 journey

Article

Author: Mitsudomi, Tetsuya

A review.Savolitinib is a targeted therapy for patients with non-small-cell lung cancer (NSCLC) harboring MET exon 14 skipping mutations, which occur in about 3% of NSCLC cases.In a recent phase 3b study involving 87 treatment-naive patients, savolitinib demonstrated an objective response rate of 62% and a disease control rate of 92%.Treatment-related adverse events were reported in 98% of patients, with peripheral edema being the most common.While the efficacy of MET inhibitors like savolitinib is promising, challenges remain in their differential use due to the heterogeneous responses compared to other targeted therapies.Further research is needed to optimize patient selection and explore the potential of type II MET inhibitors to address resistance issues.

01 Dec 2024·Lancet Respiratory Medicine

Savolitinib in patients in China with locally advanced or metastatic treatment-naive non-small-cell lung cancer harbouring MET exon 14 skipping mutations: results from a single-arm, multicohort, multicentre, open-label, phase 3b confirmatory study

Article

Author: Wang, Mengzhao ; Fan, Yun ; Shi, Jianhua ; Song, Quanyi ; Liu, Anwen ; Lu, Shun ; Ran, Fengming ; Yang, Minglei ; Wang, Linfang ; Yu, Yongfeng ; Cheng, Ying ; Lv, Dongqing ; Zhou, Jianying ; Chen, Yuan ; Wang, Buhai ; Li, Juan ; Lu, Kaihua ; Fan, Songhua ; Song, Zizheng ; Yu, Zhuang ; Su, Haichuan ; Chang, Jianhua ; Liu, Zhihua ; Zhang, Yongchang ; Luo, Xian ; Duan, Jianchun ; Min, Xuhong ; Ma, Rui ; Wang, Changli ; Zhang, Tongmei ; Wang, Pingli ; Wang, Limin ; Han, Liang ; Yu, Guohua ; Cang, Shundong ; Huang, Jianan ; Zhao, Yanqiu ; Liu, Chunling ; Song, Xia ; Dong, Xiaorong ; Wu, Lin ; Zhang, Xiaodong ; Wang, Ye ; Pan, Pinhua ; Ren, Yongxin ; Li, Xingya ; Su, Weiguo ; Zhang, Zhihong ; Fang, Jian ; Zhong, Diansheng ; Shi, Michael ; Yu, Jie ; Guo, Qisen ; Liu, Baogang ; Jin, Bo

BACKGROUND:

Savolitinib has been approved in China for advanced or metastatic non-small-cell lung cancer (NSCLC) with MET exon 14 (METex14) skipping alterations in previously treated patients and those unable to receive platinum-based chemotherapy. We report results from a treatment-naive cohort of a phase 3b study that was designed to evaluate the efficacy and safety of savolitinib in locally advanced or metastatic METex14-mutated NSCLC.

METHODS:

This single-arm, multicohort, multicentre, open-label, phase 3b study was done at 48 hospitals in China in adult (≥18 years) patients with locally advanced or metastatic METex14-mutated NSCLC who had not received previous systemic antitumour therapy. Patients with a bodyweight of 50 kg or more and those with a bodyweight of less than 50 kg received savolitinib once daily at 600 mg or 400 mg, respectively, in 21-day cycles. The primary endpoint was objective response rate assessed by independent review committee (IRC) per Response Evaluation Criteria in Solid Tumours, version 1.1. The full analysis set comprised all patients who received at least one dose of study medication, which was used to assess the efficacy endpoints and baseline and safety data. This study is registered with ClinicalTrials.gov (NCT04923945) and is closed to accrual.

FINDINGS:

Between Aug 31, 2021, and Oct 20, 2023, 125 treatment-naive patients were assessed for eligibility, of whom 87 were enrolled and received savolitinib. The median age of patients was 70·0 years (IQR 65·2-75·8) and 51 (59%) of 87 patients were male and 36 (41%) were female. In the full analysis set, the IRC-assessed objective response rate was 62% (95% CI 51-72) and the investigator-assessed objective response rate was 60% (49-70), showing a high concordance rate (84%). Treatment-related adverse events were reported in 85 (98%) of 87 patients, with peripheral oedema (54 [62%]) being the most common. Two of these treatment-related adverse events led to death (cardiac failure n=1, unknown reasons n=1).

INTERPRETATION:

Savolitinib showed manageable toxicity and promising efficacy in treatment-naive patients with advanced or metastatic METex14-mutated NSCLC.

FUNDING:

HUTCHMED and AstraZeneca.

100

News (Medical) associated with Savolitinib

20 Mar 2025

·www.globenewswire.com

HUTCHMED Highlights Savolitinib SAVANNAH Phase II and Other Data at European Lung Cancer Congress 2025

— SAVANNAH Phase II trial demonstrated high and durable response rates with savolitinib plus TAGRISSO® in MET-high lung cancer, representing a promising chemo-free oral treatment strategy to address mechanisms of resistance in the advanced setting — — Long-term survival benefit and safety observed in savolitinib Phase IIIb study in METex14 NSCLC — HONG KONG and SHANGHAI and FLORHAM PARK, N.J., March 20, 2025 (GLOBE NEWSWIRE) -- HUTCHMED (China) Limited (“HUTCHMED”) (Nasdaq/AIM:HCM; HKEX:13) today announces that new and updated data from several studies of compounds discovered by HUTCHMED, savolitinib and surufatinib, will be presented at the European Lung Cancer Congress (ELCC) 2025, taking place on March 26-29, 2025 in Paris, France. Title:SAVANNAH: Savolitinib (savo) + osimertinib (osi) in patients (pts) with EGFRm advanced NSCLC and MET overexpression (OverExp) and/or amplification (Amp) following progressive disease (PD) on osiLead Author:Myung-Ju Ahn, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of KoreaSession:Proffered Paper session 1Abstract Number: #2ODate & Time:Wednesday, March 26, 2025,16:45 Central European TimeLocation:South Paris Room Results from the SAVANNAH Phase II trial (NCT03778229) showed savolitinib (300mg BID1) plus TAGRISSO® demonstrated a clinically meaningful and durable objective response rate (“ORR”) in patients with epidermal growth factor receptor mutated (“EGFRm”) non-small cell lung cancer (“NSCLC”) with high levels of MET overexpression and/or amplification whose disease progressed on treatment with first line TAGRISSO®. Savolitinib plus TAGRISSO® demonstrated confirmed ORR of 56% (95% CI2: 45%–67%) and 55% (95% CI: 43%–66%), median duration of response (“DoR”) of 7.1 (95% CI: 5.6–9.6) and 9.9 (95% CI: 6.0–13.7) months, and median progression-free survival (“PFS”) of 7.4 (95% CI: 5.5–7.6) and 7.5 (95% CI: 6.4–11.3) months by investigator and blinded independent central review (BICR) assessment, respectively. Safety results and discontinuation rates due to adverse events were consistent with the established profiles of each medicine and no new safety concerns were reported. In all patients treated with savolitinib (300mg BID) plus TAGRISSO®, Grade 3 or higher adverse events (AEs) occurred in 57% and Grade 3 or higher treatment related adverse events (TRAEs) occurred in 32% of the patients. Savolitinib is an oral, potent and highly selective MET tyrosine kinase inhibitor (“TKI”) being jointly developed and commercialized by AstraZeneca and HUTCHMED. In 2023, savolitinib and TAGRISSO® received Fast Track Designation from the US Food and Drug Administration (FDA) in this setting. Title:Final Overall Survival and Long-term Safety Outcomes of Savolitinib in Patients with Locally Advanced or Metastatic NSCLC Harboring MET Exon 14 (METex14) Mutation: An Update from a Phase 3b Study Lead Author:Yongfeng Yu, Shanghai Chest Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, ChinaSession:Poster Display sessionAbstract Number: #80PDate & Time:Friday March 28, 2025,13:00 Central European TimeLocation:Poster area Updated results from the savolitinib Phase IIIb study in China demonstrated survival benefits and long-term safety in MET exon 14 skipping alteration NSCLC, particularly in treatment-naïve patients (NCT04923945). Among the 166 patients who received savolitinib treatment, the median follow-ups for 87 treatment-naïve patients and 79 previously treated patients were 34.5 and 25.1 months, respectively. In 87 treatment-naïve patients, median overall survival (“OS”) was 28.3 months (95% CI: 17.5–not evaluable), and the 36-month OS rate was 44.7%. In 79 previously treated patients, median OS was 25.3 months (95% CI: 20.5–30.5), and the 24-month OS rate was 51.7%. Post-hoc OS subgroup analysis suggested that patients with baseline brain metastasis also gain survival benefit with median OS of 15.3 months and 25.3 months in treatment-naïve patients (10/87 patients) and previously treated (21/79 patients) with brain metastasis, respectively. No new safety signal was observed. Savolitinib is approved in China under the brand name ORPATHYS® for this patient population. Title:Final overall survival (OS) of surufatinib plus PD-1/PD-L1 antibodies as maintenance therapy following first line (1L) platinum-based chemotherapy (Chemo) plus PD-1/PD-L1 antibodies in patients (pts) with extensive-stage small cell lung cancer (ES-SCLC)Lead Author:Yi Hu, Chinese PLA General Hospital, Beijing, ChinaSession:Poster Display sessionAbstract Number: #310PDate & Time:Friday March 28, 2025,13:00 Central European TimeLocation:Poster area Results from the exploratory study suggests surufatinib plus immunotherapy as maintenance therapy following first line chemo-immunotherapy demonstrated durable survival benefit for patients with extensive-stage small cell lung cancer (“SCLC”) patients (NCT05509699). At data cut-off on July 31, 2024, a total of 21 patients were enrolled in this single arm Phase IIa part of the study and received at least one dose of surufatinib plus PD-1/PD-L1 antibodies treatment. The median follow-up duration was 17.1 months for maintenance and 22.5 months for first line (induction + maintenance) therapy. The 12-month and 18-month OS rates were both 57.1% for maintenance therapy; and 85.7% and 57.1% for first line therapy. About NSCLC and SAVANNAH Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths. Lung cancer is broadly split into SCLC or NSCLC, the latter accounting for about 80% of cases. Approximately 10 to 15% of patients with NSCLC in the US and Europe and 30 to 40% of patients in Asia have an epidermal growth factor receptor (“EGFR”) mutation. While EGFR TKIs have significantly improved outcomes in the first line setting, treatment resistance and disease progression are extremely common, and a significant unmet need exists in later-line settings for effective and well-tolerated treatment options. SAVANNAH is an ongoing randomized, global Phase II trial studying the efficacy of savolitinib added to TAGRISSO® in patients with EGFRm, locally advanced or metastatic NSCLC with MET overexpression and/or amplification who progressed following treatment with TAGRISSO®. Based on the original single-arm trial design, patients were treated with savolitinib 300 or 600mg QD3 or 300mg BID, in combination with oral TAGRISSO® 80mg QD. In 2022, a comparison of savolitinib 300 mg BID and TAGRISSO® 80 mg QD to savolitinib 300mg BID and placebo was added to the trial to evaluate contribution of components. The trial enrolled over 360 patients in more than 80 centers globally, including in North America, Europe, South America and Asia. The primary endpoint is ORR and key secondary endpoints include PFS and DoR. In August 2022, positive interim results from the SAVANNAH trial were presented at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer (WCLC). The global SAFFRON Phase III trial is currently ongoing to further assess the savolitinib plus TAGRISSO® combination versus platinum-based doublet chemotherapy in patients with EGFRm, MET-overexpressed and/or amplified, locally advanced or metastatic NSCLC following TAGRISSO®. Patients are being prospectively selected using the high MET level cut-off identified in SAVANNAH. About Savolitinib Savolitinib is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. MET is a tyrosine kinase receptor that has an essential role in normal cell development. Savolitinib 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. MET overexpression and/or amplification can lead to tumor growth and the metastatic progression of cancer cells, and is a known mechanism of acquired resistance to EGFR TKIs. The prevalence of MET depends on the sample type, detection method and assay cut-off used. Savolitinib is approved in China and is marketed under the brand name ORPATHYS® by our partner, 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 has been included in the National Reimbursement Drug List of China (“NRDL”) since March 2023. 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 Surufatinib Surufatinib is a novel, oral angio-immuno kinase inhibitor that selectively inhibits the tyrosine kinase activity associated with vascular endothelial growth factor receptors (VEGFRs) and fibroblast growth factor receptor (FGFR), which both inhibit angiogenesis, and colony stimulating factor-1 receptor (CSF-1R), which regulates tumor-associated macrophages, promoting the body’s immune response against tumor cells. Its unique dual mechanism of action may be very suitable for possible combinations with other immunotherapies, where there may be synergistic anti-tumor effects. Surufatinib is marketed in China by HUTCHMED under the brand name SULANDA®, and was first included in the NRDL in January 2022 for the treatment of non-pancreatic and pancreatic neuroendocrine tumors (NETs). About HUTCHMED HUTCHMED (Nasdaq/AIM:HCM; HKEX:13) is an innovative, commercial-stage, biopharmaceutical company. It is committed to the discovery, 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, and the first of which is also approved around the world including in the US, Europe and Japan. For more information, please visit www.hutch-med.com or follow us on LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of the “safe harbor” provisions of the U.S. 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 the savolitinib or surufatinib for the treatment of patients with lung cancer and the further clinical development of the savolitinib or surufatinib in this and other indications. Forward-looking statements involve risks and uncertainties. Such risks and uncertainties include, among other things, assumptions regarding the timing and outcome of clinical studies and the sufficiency of clinical data to support New Drug Application approval of the savolitinib or surufatinib in lung cancer or other indications in the US, China or other jurisdictions, its potential to gain approvals from regulatory authorities on an expedited basis or at all, the safety profile of savolitinib or surufatinib, HUTCHMED’s ability to fund, implement and complete its further clinical development and commercialization plans for savolitinib or surufatinib and the timing of these events. In addition, as certain studies rely on the use of other drug products such as osimertinib as combination therapeutics with savolitinib and PD-1/PD-L1 antibodies as combination therapeutics with surufatinib, 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 U.S. Securities and Exchange Commission, on AIM and on The Stock Exchange of Hong Kong Limited. HUTCHMED undertakes no obligation to update or revise the information contained in this press release, whether as a result of new information, future events or circumstances or otherwise. Medical Information This press release 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. CONTACTS Investor Enquiries+852 2121 8200 / ir@hutch-med.com Media Enquiries FTI Consulting –+44 20 3727 1030 / HUTCHMED@fticonsulting.comBen Atwell / Alex Shaw+44 7771 913 902 (Mobile) / +44 7779 545 055 (Mobile)Brunswick – Zhou Yi+852 9783 6894 (Mobile) / HUTCHMED@brunswickgroup.com Panmure LiberumNominated Advisor and Joint BrokerAtholl Tweedie / Freddy Crossley / Rupert Dearden+44 20 7886 2500 HSBCJoint BrokerSimon Alexander / Alina Vaskina / Arnav Kapoor+44 20 7991 8888 CavendishJoint BrokerGeoff Nash / Nigel Birks+44 20 7220 0500______________________________ References and Abbreviations 1 BID = Twice per day. 2 CI = Confidence interval. 3 QD = Once per day.

Clinical ResultPhase 2ImmunotherapyFast TrackPhase 3

19 Mar 2025

·www.fiercepharma.com

AstraZeneca offers early look at Datroway-Tagrisso combo in EGFR lung cancer as phase 3 trial rolls on

AstraZeneca recently launched the phase 3 Tropion-Lung15 trial—testing Datroway either by itself or with Tagrisso—in post-Tagrisso EGFR-mutated non-small cell lung cancer. As AstraZeneca awaits an FDA decision for its Daiichi Sankyo-partnered Datroway in EGFR-mutated non-small cell lung cancer (NSCLC), the British pharma has rolled out early data from a trial combining the antibody-drug conjugate (ADC) with its old blockbuster Tagrisso.A combination of Datroway and Tagrisso induced a response in 36% of patients with EGFR-mutant NSCLC who had progressed on first-line Tagrisso, new data show.The data come from module 10 of the phase 2 Orchard trial, a platform study of novel combinations in the post-Tagrisso setting. The findings are part of an abstract set to be presented at the European Lung Cancer Congress (ELCC) next week.The 36% objective response rate (ORR) was recorded among 33 evaluable patients who received Datroway at 6 milligrams per kilogram of body weight, which is the recommended dose for the TROP2-directed ADC’s FDA-approved indication in third-line HR-positive, HER2-negative breast cancer.Among 35 patients who received Datroway at a lower 4 mg/kg dose, investigators recorded a 43% ORR for the combination. The two patient groups had similar follow-up times at about 13 months.Considering the overall benefit-risk profiles of the two doses, investigators recommended the 6 mg/kg option, according to the abstract.In October, AZ and Daiichi launched the phase 3 Tropion-Lung15 trial testing Datroway 6 mg/kg—either by itself or with Tagrisso—in post-Tagrisso EGFR-mutant NSCLC. The study bears an estimated primary completion date in June 2026.Cancer that becomes resistant to Tagrisso may still have tumor cells that harbor EGFR mutations, an AstraZeneca spokesperson explained in offering the company’s rationale for adding Tagrisso to Datroway in second-line treatment.“Continuing Tagrisso ensures ongoing inhibition against those EGFRm-driven tumor cells, while also receiving treatment to suppress the resistance and, ultimately, prolong patients’ responses to treatment,” the spokesperson said in a statement. Besides the ORR measure, the higher dose of Datroway can trigger a response faster and keep tumors at bay longer, investigators found. The median time to onset of response was 1.4 months versus 2.7 months, respectively, for the two doses. Investigators estimated that only 15% of patients who received the lower dose would remain in response at nine months, whereas 64% on the preferred dose could enjoy that status.Patients on the higher Datroway dose went a median 11.7 months without disease progression, compared with 9.5 months among recipients of the lower dose, the data show.As expected, the combination with the higher dose was linked to more adverse events, although no new safety signals emerged.Overall, 56% and 34% of patients given the high and low doses, respectively, experienced grade 3 or above treatment-related adverse events. Adverse events leading to Datroway dose reductions were recorded in 59% and 23% of patients in the two groups, respectively.Interstitial lung disease or pneumonitis, a side effect that experts are watching closely for all ADCs based on Daiichi’s DXd platform, was seen in 15% of patients on the high dose, including 6% at grade 3 or above.Before the latest Datroway-Tagrisso combo readout, AZ and Daiichi have applied for FDA approval of Datroway as a monotherapy in previously treated EGFR-mutated NSCLC. A decision from the agency is expected by July 12, 2025.That submission was based on a pooled analysis of certain patients from the phase 3 Tropion-Lung01 and the phase 2 Tropion-Lung05 trials. Among 117 patients with EGFR-mutated NSCLC who had tried a median of three prior lines of therapy, Datroway alone achieved an ORR of 43% in the analysis, with the responses lasting for a median of seven months. For years, Tagrisso has been the standard first-line treatment for EGFR-mutated NSCLC. But that status has recently come under attack from Johnson & Johnson’s combination of Rybrevant and Lazcluze. Rybrevant, an EGFRxMET bispecific antibody, is also approved in combination with chemotherapy following treatment with an EGFR inhibitor such as Tagrisso.In the phase 3 Mariposa-2 trial conducted in post-Tagrisso patients, the Rybrevant-chemo regimen registered a 53% ORR, with a 6.9-month duration of response. The combo significantly reduced the risk of progression or death by 52% versus chemo alone. The median progression-free survival for the combo was 6.3 months.The latest Orchard data for AZ’s Datroway-Tagrisso cocktail look competitive, with the inherent drawbacks of cross-trial comparisons in mind. Other data at ELCCBesides Orchard, AZ also shared the primary analysis of the phase 2 Savannah trial, which evaluated Tagrisso in tandem with Hutchmed-partnered MET inhibitor savolitinib, which is approved in China under the brand name Orpathys. The analyzed patients had EGFR-mutant NSCLC with high MET overexpression or amplification following treatment with first-line Tagrisso.The combo logged a 56% ORR by investigator assessment or 55% by blinded central review among 80 patients who met a high MET expression criterion. The median duration of response was 7.1 months and 9.9 months, respectively, based on the separate types of review. And the median progression-free survival was 7.4 months and 7.5 months, respectively. The primary efficacy analysis focused on a cohort of patients who received Orpathys doses more frequently than the regimen studied as part of a 2022 readout, in which AZ reported a 49% ORR.Phase 3 results from the Saffron trial utilizing the more frequent, twice-a-day Orpathys regimen together with Tagrisso are expected in the second half of 2025. The trial includes patients who have progressed on either first- or second-line treatment with Tagrisso.Editor's Note: The story has an updated statement from AstraZeneca.

Clinical ResultPhase 3Phase 2Drug ApprovalADC

17 Mar 2025

·pipelinereview.com

Imfinzi approved in the EU as first and only immunotherapy for limited-stage small cell lung cancer

Approval based on ADRIATIC Phase III trial results which showed a 27% reduction in the risk of death versus placebo LONDON, UK I March 17, 2025 I AstraZeneca’s Imfinzi (durvalumab) has been approved in the European Union (EU) as monotherapy for the treatment of adults with limited-stage small cell lung cancer (LS-SCLC) whose disease has not progressed following platinum-based chemoradiation therapy (CRT). 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 ADRIATIC Phase III trial, which were published in The New England Journal of Medicine . SCLC is a highly aggressive form of lung cancer, with an estimated 8,000 people treated for LS-SCLC across the five major European countries each year. 1-2 LS-SCLC typically recurs and progresses rapidly, despite initial response to standard-of-care chemotherapy and radiotherapy. 3-4 The prognosis for LS-SCLC is particularly poor, as only 15-30% of patients survive for five years after diagnosis. 5 Suresh Senan, PhD, radiation oncologist at the Amsterdam University Medical Centers, The Netherlands, and principal investigator in the trial, said: “This approval marks a turning point for patients with limited-stage small cell lung cancer in Europe, bringing them an immunotherapy option for the first time. An unprecedented 57% of patients treated with durvalumab were still alive at three years in the ADRIATIC trial. This significant advance establishes a new benchmark in a setting where the standard of care has remained unchanged for decades.” Dave Fredrickson, Executive Vice President, Oncology Haematology Business Unit, AstraZeneca, said: “Imfinzi has the potential to transform how limited-stage small cell lung cancer is treated as the first immunotherapy approved in Europe in this setting. As the only immunotherapy approved for both early and late-stage disease, Imfinzi is poised to become the foundation for transforming outcomes for people with small cell lung cancer.” In the trial, results showed Imfinzi reduced the risk of death by 27% versus placebo (based on an overall survival [OS] hazard ratio [HR] of 0.73; 95% confidence interval [CI] 0.57-0.93; p=0.0104). Estimated median OS was 55.9 months for Imfinzi versus 33.4 months for placebo. An estimated 57% of patients treated with Imfinzi were alive at three years compared to 48% for placebo. Imfinzi also reduced the risk of disease progression or death by 24% (based on a progression-free survival [PFS] HR of 0.76; 95% CI 0.61-0.95; p=0.0161) versus placebo. Median PFS was 16.6 months for Imfinzi versus 9.2 months for placebo. An estimated 46% of patients treated with Imfinzi had not experienced disease progression at two years compared to 34% for placebo. The safety profile for Imfinzi was generally manageable and consistent with the known profile of this medicine. No new safety signals were observed. Imfinzi is approved in the US and several other countries in this setting based on the ADRIATIC results. Regulatory applications are currently under review in Japan and several other countries for this indication. Imfinzi is also approved in combination with chemotherapy for the treatment of extensive-stage SCLC based on the CASPIAN Phase III trial. Notes Small cell 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 non-small cell lung cancer (NSCLC) and SCLC, with about 15% of cases classified as SCLC. 8 LS-SCLC (Stage I-III) accounts for approximately 30% of SCLC diagnoses and is classified when the disease is generally only in one lung or one side of the chest. 9 The prognosis for patients with LS-SCLC remains poor despite curative-intent treatment with standard-of-care concurrent CRT (cCRT). 10 ADRIATIC The ADRIATIC trial is a randomised, double-blind, placebo-controlled, multi-centre global Phase III trial evaluating Imfinzi monotherapy and Imfinzi plus Imjudo (tremelimumab) versus placebo in the treatment of 730 patients with LS-SCLC who had not progressed following cCRT. In the experimental arms, patients were randomised to receive a 1500mg fixed dose of Imfinzi with or without Imjudo 75mg every four weeks for up to four doses/cycles each, followed by Imfinzi every four weeks for up to 24 months. The dual primary endpoints were PFS and OS for Imfinzi monotherapy versus placebo. Key secondary endpoints included OS and PFS for Imfinzi plus Imjudo versus placebo, safety and quality of life measures. The trial included 164 centres in 19 countries across North and South America, Europe 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 response s. In addition to its indications in SCLC, Imfinzi is also the global standard of care based on OS in the curative-intent setting of unresectable, Stage III NSCLC in patients whose disease has not progressed after CRT. Additionally, Imfinzi is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC; and in combination with a short course of Imjudo and chemotherapy for the treatment of metastatic NSCLC. 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 event-free survival in the MATTERHORN Phase III trial in resectable gastric and gastroesophageal junction cancers. Imfinzi in combination with chemotherapy followed by Imfinzi monotherapy is approved as a 1 st -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. National Cancer Institute. NCI Dictionary – Small Cell Lung Cancer. Available at: https://www.cancer.gov/publications/dictionaries/cancer-terms/def/small-cell-lung-cancer . Accessed March 2025. 2. AstraZeneca PLC. Investor Relations Epidemiology Spreadsheet. Available at: https://www.astrazeneca.com/investor-relations.html . Accessed March 2025. 3. Qin A, Kalemkerian GP. Treatment Options for Relapsed Small-Cell Lung Cancer: What Progress Have We Made? J Oncol Pract . 2018;14(6):369-370. 4. Cheng Y, et al. Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer. N Engl J Med . 2024;391(14):1313-1327. 5. Bebb DG, et al. Symptoms and Experiences with Small Cell Lung Cancer: A Mixed Methods Study of Patients and Caregivers. Pulm Ther . 2023;9:435-450. 6. World Health Organization. International Agency for Research on Cancer. Lung Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/cancers/15-trachea-bronchus-and-lung-fact-sheet.pdf . Accessed March 2025. 7. World Health Organization. International Agency for Research on Cancer. World Fact Sheet. Available at: https://gco.iarc.who.int/media/globocan/factsheets/populations/900-world-fact-sheet.pdf . Accessed March 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 March 2025. 9. American Cancer Society. Small Cell Lung Cancer Stages. Available at: https://www.cancer.org/cancer/types/lung-cancer/detection-diagnosis-staging/staging-sclc.html . Accessed March 2025. 10. Senan S, et al. ADRIATIC: A phase III trial of durvalumab ± tremelimumab after concurrent chemoradiation for patients with limited stage small cell lung cancer. Ann Oncol . 2019;30(suppl. 2):ii25. SOURCE: AstraZeneca

ImmunotherapyPhase 3Clinical ResultDrug Approval

100 Deals associated with Savolitinib

External Link

KEGG	Wiki	ATC	Drug Bank
D11139	Savolitinib	L01XE	DB12048

R&D Status

Approved

10 top approved records.

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Indication	Country/Location	Organization	Date
MET Exon 14 Skipping Mutation Non-small Cell Lung Cancer	China	Hutchison MediPharma Ltd.	22 Jun 2021

Developing

10 top R&D records.

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Indication	Highest Phase	Country/Location	Organization	Date
Non-Small Cell Lung Cancer	NDA/BLA	China	Hutchison MediPharma Ltd.	31 Dec 2024
Papillary Renal Cell Carcinoma	NDA/BLA	-	HUTCHMED (China) Ltd.	06 Jun 2022
Stomach Cancer	NDA/BLA	China	HUTCHMED (China) Ltd.	06 Jun 2022
Carcinoma	Phase 3	United States	AstraZeneca PLC	03 Aug 2022
Carcinoma	Phase 3	Japan	AstraZeneca PLC	03 Aug 2022
Carcinoma	Phase 3	Austria	AstraZeneca PLC	03 Aug 2022
Carcinoma	Phase 3	Belgium	AstraZeneca PLC	03 Aug 2022
Carcinoma	Phase 3	Bulgaria	AstraZeneca PLC	03 Aug 2022
Carcinoma	Phase 3	Greece	AstraZeneca PLC	03 Aug 2022
Carcinoma	Phase 3	Malaysia	AstraZeneca PLC	03 Aug 2022

Clinical Result

Indication

Phase

Evaluation

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Study	Phase	Population	Analyzed Enrollment	Group	Results	Evaluation	Publication Date


NCT04606771 (CoC, CTgov)	Phase 2	MET gene amplification Non-small Cell Lung Cancer	30	Savolitinib+Osimertinib (Savolitinib Plus Osimertinib)	dbbhyqyeny = yuwgotiipt spagpapdeu (ygkcvmatko, cholxnpiez - ldekocnunz) View more	-	24 Sep 2024
				Placebo+Savolitinib (Savolitinib Plus Placebo)	dbbhyqyeny = gthunoqlvh spagpapdeu (ygkcvmatko, eljpsdhjqt - romjjaboel) View more
NCT04923932 (phase II study of savolitinib in patients with MET-amplified gastroesophageal junction adenocarcinomas or gastric cancer, ESMO2024)	Phase 2	c-Met positive Gastroesophageal junction adenocarcinoma \| Stomach Cancer METamp	34	Savolitinib 600/400 mg QD	namnyxrfpn(fzpitcddnj) = mixxbkhsgc vlndwjyipz (miiummtfoj )	Positive	16 Sep 2024
				Savolitinib 300/200 mg BID	namnyxrfpn(fzpitcddnj) = nrmkwtsjtn vlndwjyipz (miiummtfoj )
NCT04923945 (Pubmed \| Lancet Respir Med) Manual	Phase 3	MET Exon 14 Skipping Mutation Non-small Cell Lung Cancer First line MET Exon 14 Skipping	87	Savolitinib 600 mg	zjoexvvlaj(ewgframwrl) = aktuuelwtf tackgdcbhd (psnxzbevee, 51 - 72) View more	Positive	10 Sep 2024
NCT02761057 (S1500, Pubmed \| J Clin Oncol) Manual	Phase 2	Papillary Renal Cell Carcinoma Second line \| First line	147	Sunitinib	kekkgrnnkq(nomhspwwgl) = zlwoitcrae jcdpsvtclk (ujybvsblxm, 12.8 - 21.8) View more	Negative	10 Sep 2024
				Cabozantinib	kekkgrnnkq(nomhspwwgl) = gwnymcvswy jcdpsvtclk (ujybvsblxm, 12.0 - 28.1) View more
WCLC2024 Manual	Not Applicable	c-Met positive non-small cell lung cancer First line MET Amplification \| MET Exon 14 Skipping	4	Savolitinib 600mg once daily	nqvulciael(cbhhqcdvds) = hcwoegqrdi ymnsmuevms (nrodlugtqy ) View more	Positive	07 Sep 2024
				Savolitinib (Patient case 2)	nqvulciael(cbhhqcdvds) = tvhpjqtiks ymnsmuevms (nrodlugtqy ) View more
WCLC2024 Manual	Not Applicable	MET Exon 14 Skipping Mutation Non-small Cell Lung Cancer First line MET Exon 14 Skipping	3	Savolitinib 600 mg Qd	zjdoizeixa(kefdpjnkuk) = smwvscflfh olijbuipms (ryfpjmbcmh )	Positive	07 Sep 2024
				Savolitinib 400 mg Qd	zjdoizeixa(kefdpjnkuk) = zbpagkljjp olijbuipms (ryfpjmbcmh )
WCLC2024 Manual	Not Applicable	EGFR mutation MET positive Non-small Cell Lung Cancer EGFR Mutation \| MET Overexpression	6	Savolitinib 400mg daily + Osimertinib 80mg once daily	rdyvfscper(wfcgrxxeiv) = dbfxbhpxjd kdymxdlwrf (vwehteizux, 8.8 - 23.3) View more	Positive	07 Sep 2024
WCLC2024 Manual	Not Applicable	EGFR mutation MET positive Non-small Cell Lung Cancer MET Mutation (Activating) \| EGFR Mutation	3	Savolitinib	mfctuholpr(phhvgbiwvh) = Patient 1 had only mild adverse reactions (increased aminotransferase, grade 2; edema, grade 2), which were resolved after symptomatic treatment. Patient 2 had no adverse events related to the treatment. Patient 3 experienced adverse events during chemotherapy and anti-angiogenic therapy, but no specific details were provided. ndyfamjhim (iwefhfcrbj )	Positive	07 Sep 2024
				Savolitinibation EGFR-TKI
WCLC2024 Manual	Not Applicable	EGFR mutation MET positive Non-small Cell Lung Cancer First line MET Amplification \| EGFR Mutation	3	Savolitinib 40Osimertinibsimertinib 80 mg QD	mvmeyaidoe(urdxrdsopb) = fysbslbzzi ecqimrrtzr (zcuxelqnxz ) View more	Positive	07 Sep 2024
				Savolitinib + Osimertinib (patient 2)	mvmeyaidoe(urdxrdsopb) = wiyxbvngce ecqimrrtzr (zcuxelqnxz ) View more
NCT04606771 (AACR2024) Manual	Phase 2	Non-Small Cell Lung Cancer MET Amplification	30	Savolitinib 300 mg QD + Osimertinib 80 mg QD (MET FISH10+ and/or IHC90+)	tlknckrxlh(xskmzaxzgl) = abqrmsecuf fdpbydgczg (xpimfpeapf, 24 - 91) View more	Positive	09 Apr 2024
				Savolitinib 300 mg QD + Osimertinib 80 mg QD	tlknckrxlh(xskmzaxzgl) = ycyiowwapa fdpbydgczg (xpimfpeapf, 29 - 82) View more

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