Orpathys (savolitinib) / AstraZeneca, Hutchmed - LARVOL DELTA

Savolitinib (Savo) combined with osimertinib (osi) versus chemotherapy (chemo) in EGFR-mutant (EGFRm) and MET-amplification (METamp) advanced NSCLC after disease progression (PD) on EGFR tyrosine kinase inhibitor (TKI): Results from a randomized phase 3 SACHI study. (BASCO-MN 2025) - No abstract available

Clinical • Late-breaking abstract • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR • MET

Construction of a prognostic model for lung adenocarcinoma based on necroptosis genes and its exploration of the potential for tumor immunotherapy. (PubMed, Transl Cancer Res) - "Significant differences (P<0.05) were found between the high and low risk groups in terms of immune function and half-maximal inhibitory concentration (IC50) values of five anticancer drugs (doxorubicin, lapatinib, paclitaxel, savolitinib and trametinib). We also identified a lncRNA SNHG14 /hsa-miR-101-3p/KL/PLK1 regulatory axis for LUAD. The survival prognosis model of NRGs constructed in this study can predict the prognosis and immune microenvironment of LUAD patients."

IO biomarker • Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • PLK1 • SNHG14

CoC: A Study Comparing Savolitinib Plus Osimertinib vs Savolitinib Plus Placebo in Patients With EGFRm+ and MET Amplified Advanced NSCLC (clinicaltrials.gov) - P2 | N=30 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Mar 2025 ➔ Mar 2026

Trial completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

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 (GlobeNewswire) - "HUTCHMED (China) Limited...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...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."

China approval • Lung Non-Squamous Non-Small Cell Cancer

Hutchmed to get milestone payment after China drug approval (Sharecast) - "Hutchmed announced on Monday that China’s National Medical Products Administration (NMPA) has approved the new drug application for the combination of ‘Orpathys’. Or savolitinib, and ‘Tagrisso’, or osimertinib, to treat patients with locally advanced or metastatic EGFR mutation-positive non-squamous non-small cell lung cancer (NSCLC) with MET amplification following progression on EGFR TKI therapy. The AIM-traded firm said the approval triggered an $11m milestone payment from AstraZeneca, which markets both drugs in China."

Financing • Non Small Cell Lung Cancer

SPRING: Study of Precision Treatment for Rare Tumours in China Guided by PDO and NGS (clinicaltrials.gov) - P2 | N=200 | Not yet recruiting | Sponsor: Peking University Shenzhen Hospital

Biomarker • New P2 trial • Oncology

Efficacy and CNS results from a randomized subset of the phase 2 SAVANNAH study comparing savolitinib (savo) + osimertinib (osi) combination with savo + placebo (PBO). (ASCO 2025) - P2 | "In EGFRm advanced NSCLC with MET IHC3+/≥90% and/or FISH10+ status after PD on 1L osi, efficacy of savo 300 mg BID + osi was numerically greater than savo + PBO and showed promising CNS activity. To date, this is one of the largest randomized data sets presented evaluating an oral MET-TKI in EGFRm NSCLC. Efficacy findings from SAVANNAH suggest that targeting both EGFR and MET is key and support further investigation of savo + osi and CNS activity in the Phase 3 SAFFRON study."

Clinical • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • Thoracic Cancer • MET

Savolitinib (Savo) combined with osimertinib (osi) versus chemotherapy (chemo) in EGFR-mutant (EGFRm) and MET-amplification (METamp) advanced NSCLC after disease progression (PD) on EGFR tyrosine kinase inhibitor (TKI): Results from a randomized phase 3 SACHI study. (ASCO 2025) - P3 | "Eligible pts were randomly assigned (1:1) to receive savo 400 or 600 mg QD (for body weight of < 50, or ≥ 50 kg respectively) + osi 80 mg QD, or chemo (pemetrexed + carboplatin/cisplatin), stratified by brain metastases, prior use of 3G EGFR-TKI, and type of EGFR mutations... From 15 Oct 2021 to 30 Aug 2024 (DCO for IA), 211 pts were randomized to receive savo + osi or chemo (n=106 vs 105)... Savo + osi significantly improved PFS versus chemo in METamp NSCLC post EGFR-TKI, and the combination was safe and well tolerated. Savo + osi is a potential new treatment option for this genomically defined population. *52.4% of pts in chemo group were crossover to receive savo + osi or other MET Inhibitors."

Clinical • Late-breaking abstract • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Savolitinib plus osimertinib in epidermal growth factor receptor (EGFR)-mutated advanced non-small cell lung cancer with MET overexpression and/or amplification following disease progression on osimertinib: primary results from the phase II SAVANNAH study. (PubMed, Ann Oncol) - P2 | "Savolitinib 300 mg b.i.d. plus osimertinib demonstrated high, clinically meaningful and durable responses in patients with EGFR-mutated, advanced NSCLC with MET IHC3+/≥90% and/or FISH10+ status following progression on first-line osimertinib. The combination was well tolerated and may provide a new oral targeted treatment approach in this setting."

Journal • P2 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

HUTCHMED Highlights SACHI Phase III Study Data Presented at the 2025 ASCO Annual Meeting (GlobeNewswire) - P3 | N=250 | SACHI (NCT05015608) | Sponsor: Hutchison Medipharma Limited | "As of the interim analysis data cut-off of August 30, 2024, a total of 211 patients were randomized to receive the savolitinib and osimertinib combination or chemotherapy. In the intention to treat (ITT) population, the median progression-free survival ('PFS') assessed by investigator was 8.2 months with savolitinib plus osimertinib, compared to 4.5 months with chemotherapy (hazard ratio ['HR'] 0.34; 95% confidence interval ['CI'] 0.23-0.49; p < 0.0001). The independent review committee ('IRC') assessed median PFS was 7.2 months vs 4.2 months, respectively (HR 0.40; 95% CI 0.28-0.59; p < 0.0001). The investigator-assessed objective response rate (ORR) was 58% in the savolitinib plus osimertinib group compared to 34% for patients in the chemotherapy group. The disease control rate (DCR) was 89% vs 67% and the median duration of response (DoR) was 8.4 months..."

Late-breaking abstract • P3 data • Non Small Cell Lung Cancer

HUTCHMED Highlights Clinical Data to be Presented at the 2025 ASCO Annual Meeting (GlobeNewswire) - "HUTCHMED (China) Limited...announces that new data from several studies of compounds discovered by HUTCHMED including savolitinib, ranosidenib, fruquintinib and surufatinib, will be presented at the American Society of Clinical Oncology (“ASCO”) Annual Meeting taking place on May 30 – June 3, 2025 in Chicago, USA."

Clinical data • pMMR • Cholangiocarcinoma • Colorectal Cancer • Endometrial Cancer • Esophageal Squamous Cell Carcinoma • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Glioma • Hepatocellular Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Osteosarcoma • Ovarian Cancer • Pancreatic Ductal Adenocarcinoma

Savolitinib for Treating Gastric Cancer and Esophagogastric Junction Adenocarcinoma Patients (clinicaltrials.gov) - P2 | N=75 | Active, not recruiting | Sponsor: Hutchison Medipharma Limited | Recruiting ➔ Active, not recruiting | Trial completion date: Oct 2025 ➔ Dec 2026 | Trial primary completion date: Apr 2025 ➔ Dec 2026

Enrollment closed • Trial completion date • Trial primary completion date • Esophageal Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Oncology • Solid Tumor • MET

SACHI: Study on Savolitinib Combined With Osimertinib in Treatment of Advanced NSCLC With MET Amplification (clinicaltrials.gov) - P3 | N=250 | Active, not recruiting | Sponsor: Hutchison Medipharma Limited | Trial completion date: Nov 2024 ➔ Dec 2025 | Trial primary completion date: Sep 2024 ➔ Dec 2025 | Recruiting ➔ Active, not recruiting

Enrollment closed • Trial completion date • Trial primary completion date • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Copy number gain of MET gene with low level in a metastatic lung adenocarcinoma patient represents response to salvage treatment with savolitinib and osimertinib: a case report. (PubMed, Front Oncol) - "We considered that a regimen of savolitinib + osimertinib combination sometimes may still be potentially beneficial for NSCLC patients with low-GCN-level MET amplification. However, it needs further confirmation in a larger cohort."

Journal • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

AstraZeneca’s record seventh year of plenary data at ASCO furthers ambition to redefine breast cancer care and transform outcomes in gastric cancer (AstraZeneca Press Release) - "AstraZeneca advances its ambition to eliminate cancer as a cause of death with new data across its diverse, industry-leading portfolio and pipeline at the American Society of Clinical Oncology (ASCO) Annual Meeting, 30 May to 3 June 2025. More than 80 abstracts will feature 20 approved and potential new medicines from the Company including two plenary presentations, one special late-breaking oral abstract session and 19 additional oral presentations."

Clinical data • Bladder Cancer • Cervical Cancer • Cholangiocarcinoma • Endometrial Cancer • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Hepatocellular Cancer • HER2 Negative Breast Cancer • HER2 Positive Breast Cancer • Hormone Receptor Positive Breast Cancer • Non Small Cell Lung Cancer • Small Cell Lung Cancer

Potential novel interventions of oncohistones, epigenetic modifications, and RNA processing machinery in betel-nuts related HNSCC in Taiwan (AACR 2025) - "PI3K/AKT/mTOR interventions, ALK/IGF1R inhibitor, CDK4/6 inhibitor, BCl2 inhibitor, WEE1 inhibitor, ATR inhibitor, DNA-PK inhibitor, AT2AR inhibitor, Mcl-1 inhibitor, MEK1/2 inhibitor, JAK2 inhibitor, CXCR4 inhibitor, FAK inhibitor, p53 reactivator, MDM2 inhibitor, SHP2 inhibitor, PARP7 inhibitor, IAP inhibitor, GLS1 inhibitor, eribulin, & VEGFR2/ PDGFR/FGFR or VEGFR2/c-MET/Axl triple blockage might be effective on TW2.6 and reverse treatment refractoriness, through the inhibition of mesenchymal transformation, pRB, & PI3K/AKT /mTOR signaling and modulation of stemness & PD1/PDL1 pathway...Disrupting NSD1 in HNSCC cell lines led to CpG hypomethylation & enhanced cisplatin sensitivity. TW2.6 used to test (1)in vitro drug sensitivity to (a)Chemical Modulators of Splicing; (b)PRMT5 inhibitor; (c)CDK9 inhibitor, EZH2i, DNMT3i, BRD/BET4i, and HDACi; (d)NSD1/SETD2 inhibitor; (e)METTL3 inhibitor; (2)synergistic effects with other therapies by MTT assay, colony..."

IO biomarker • Head and Neck Cancer • Oncology • Squamous Cell Carcinoma of Head and Neck • AKT1 • ALK • ARID1B • ATM • AXL • BRD4 • CCND3 • CDK12 • CXCR4 • DDR2 • EPHB1 • FAT1 • FGF10 • FGFR • FLCN • HRAS • KDM5A • KDR • METTL3 • MITF • NSD1 • PDGFRB • PIK3CA • RICTOR • RPS6KB1 • SDHA • SETD2 • SOX9 • STK11 • TERT • TIPARP • TMB • TNFAIP3

A bioinformatics-driven approach to identify biomarkers and elucidate the pathogenesis of type 2 diabetes concurrent with pulmonary tuberculosis. (PubMed, Sci Rep) - "Seven drugs (ERK_440_1713, JAK_8517_1739, Palbociclib_1054, PLX.4720_1036, Savolitinib_1936, Selumetinib_1736, and VX.11e_2096) exhibited significant sensitivity in patients with high-expression or low-expression of C1QA. Five genes (C1QA, MMP8, MMP9, CD248, and LINC00278) have potential as diagnostic markers for PTB + T2DM, and three genes (C1QA, MMP8, and MMP9) were upregulated in the peripheral blood of PTB + T2DM patients. Our findings may serve as a valuable reference for future research and clinical applications."

Biomarker • Journal • Diabetes • Infectious Disease • Metabolic Disorders • Pulmonary Disease • Respiratory Diseases • Tuberculosis • Type 2 Diabetes Mellitus • C1QA • CEACAM8 • COL1A2 • IL17A • MAPK4 • MIR25 • MIR363 • MIR671 • MIR942 • MMP8 • MMP9

SAMETA: Savolitinib Plus Durvalumab Versus Sunitinib and Durvalumab Monotherapy in MET-Driven, Unresectable and Locally Advanced or Metastatic PRCC (clinicaltrials.gov) - P3 | N=148 | Active, not recruiting | Sponsor: AstraZeneca | Trial completion date: Jun 2026 ➔ Oct 2025

Monotherapy • Trial completion date • Genito-urinary Cancer • Oncology • Papillary Renal Cell Carcinoma • Renal Cell Carcinoma • Solid Tumor

A case report of acute hepatic and renal failure associated with savolitinib treatment in advanced lung adenocarcinoma. (PubMed, AME Case Rep) - "Unfortunately, the patient succumbed to her illness two days after admission, despite supportive measures including continuous renal replacement therapy. This case underscores the importance of monitoring liver and kidney function in patients receiving savolitinib to facilitate the early detection and management of potentially fatal adverse reactions."

Journal • Autoimmune Hepatitis • Chronic Kidney Disease • Hepatology • Immunology • Infectious Disease • Liver Failure • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Renal Calculi • Renal Disease • Respiratory Diseases • Solid Tumor • MET

Evolving treatment for advanced Non-small cell lung cancer harbouring common EGFR activating mutations. (PubMed, Crit Rev Oncol Hematol) - "Efforts to extend disease control have led to various upfront intensification strategies, including combining EGFR TKIs with antiangiogenics or chemotherapy (e.g., the FLAURA-2 trial), and pairing novel bispecific antibodies such as amivantamab with third-generation TKIs...Emerging therapies targeting MET amplification (e.g., savolitinib plus osimertinib), leveraging antibody-drug conjugates (e.g., patritumab deruxtecan), or adding immunotherapy and antiangiogenics have shown preliminary promise in overcoming resistance...Ultimately, the evolving landscape of EGFR-mutant NSCLC underscores the need for refined biomarker-driven approaches and personalized regimens to achieve further gains in survival. In this review, we discuss these strategies in detail, highlighting current evidence and future directions for EGFR-mutant NSCLC treatment."

IO biomarker • Journal • Review • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

HUTCHMED Highlights Data to be Presented at AACR Annual Meeting 2025 (GlobeNewswire) - "HUTCHMED (China) Limited...announces that new and updated data from several studies of compounds discovered by HUTCHMED including savolitinib, fruquintinib and surufatinib, which will be presented at the upcoming American Association of Cancer Research (AACR) Annual Meeting 2025..."

Clinical data • pMMR • Preclinical • Appendix Cancer • Colorectal Cancer • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Pancreatic Cancer

Orpathys: Data from P2 trial (NCT04923932) for gastric or gastroesophageal junction adenocarcinoma in H1 2025 (AstraZeneca) - Q1 2025 Results

P2 data • Gastric Cancer • Gastroesophageal Junction Adenocarcinoma • Gastrointestinal Cancer • Oncology

SAVANNAH: Clearance of plasma EGFRm in patients with EGFRm MET-overexpressed (OverExp) and/or -amplified (Amp) NSCLC post-osimertinib (osi) treated with savolitinib (savo) + osi (AACR 2025) - P2 | "In SAVANNAH, among pts with detected EGFRm ctDNA at BL, clearance at Wk 3 was associated with improved ORR and PFS. Plasma EGFRm clearance at Wk 3 is enriched in pts with MET IHC3+/≥90% or FISH10+ status, consistent with improved efficacy in this biomarker subgroup."

Clinical • Late-breaking abstract • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

A phase I open-label positron-emission tomography study to determine brain exposure of [11C]savolitinib in healthy volunteers (AACR 2025) - "The use of savolitinib in combination with osimertinib is currently being evaluated in NSCLC patients with EGFR mutations and MET amplification. PET brain imaging in healthy volunteers showed that savolitinib penetrates the BBB and distributes to the brain following IV injection of a microdose of [11C]savolitinib."

Clinical • P1 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Patient-derived organoids as a screening platform to identify mechanisms of osimertinib resistance in non-small cell lung cancer (AACR 2025) - "The c-MET inhibitor capmatinib was specifically potent in LPTO245 but not in other models. This finding was confirmed using savolitinib, another selective c-MET inhibitor, suggesting the observed effects were due to on-target c-MET inhibition...Additionally, we identified an inverse sensitivity correlation between osimertinib and the Aurora kinase B inhibitor AZD2811 across all 6 models (r = -0.64; p = 0.03)... Our screening platform can provide novel biological insights into osimertinib resistance. Moreover, it can potentially identify drug combinations with immediate clinical utility in NSCLC, particularly with approved and clinical-grade drugs."

Clinical • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • AURKB • BRD4 • CDK4 • EGFR • PLK1 • ROS1