Orpathys (savolitinib) / AstraZeneca, Hutchmed - LARVOL DELTA

Case Report: Two cases of non-small cell lung cancer with coexistence of NTRK2 fusion and EGFR mutations. (PubMed, Front Oncol) - "Case 1 received osimertinib combined with savolitinib, had 33 months of follow-up, and achieved a partial response. Case 2 received furmonertinib and achieved a complete response. NTRK2 fusion coexisting with EGFR mutations is a rare molecular characteristic of non-small cell lung cancer, accompanied by positive PD-L1 expression, and may serve as a promising biomarker for targeted therapy."

IO biomarker • Journal • Tumor mutational burden • Lung Adenocarcinoma • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • FGFR1 • MET • Napsin A • NKX2-1 • NTRK2 • PD-L1 • TMB

MET testing and treatment (tx) sequencing after progression of disease (PD) on first-line (1L) osimertinib (osi) in patients (pts) with EGFRm advanced NSCLC and acquired MET overexpression and/or amplification (OverExp/Amp): Final analysis of a global real-world (rw) study (ESMO Asia 2025) - P2 | "Background: In the phase II SAVANNAH study (NCT03778229), osi 80 mg QD + savolitinib 300 mg BID demonstrated clinically meaningful and durable responses in EGFRm advanced NSCLC with MET OverExp/Amp after PD on 1L osi...MET-TKIs (tepotinib 52%, capmatinib 31%) and EGFR-TKIs (osi 91%) were the most common 2L txs (29% and 24%), followed by chemotherapy (CT 20%; most frequently platinum doublet 73%)... In this rw analysis, most pts had acquired MET Amp detected with NGS and limited detection of OverExp/Amp with IHC/FISH, likely indicating underutilisation of these assays. MET-TKIs and 3rd-gen EGFR-TKIs were most commonly used following PD on 1L osi and in pts with high MET cutoffs."

Clinical • Metastases • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

Progression pattern in patients (pts) with EGFR-mutant (EGFRm), MET-amplified (METamp) advanced NSCLC treated with savolitinib (savo) plus osimertinib (osi) (ESMO Asia 2025) - P3 | "The proportion of progression characterized by new lesions was numerically lower in pts treated with savo+osi compared to those with chemo. Across all progression patterns, pts treated with savo+osi had longer duration to progression, particularly in delaying the progression development of new brain and lung metastases."

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

Analysis of MET amplification (METamp) with FISH and NGS method in SACHI trial (ESMO Asia 2025) - P3 | "Background: In the Phase 3 SACHI trial (NCT05015608), savolitinib (savo) combined with osimertinib (osi) significantly improved progression-free survival (PFS) versus chemotherapy (pemetrexed plus carboplatin or cisplatin) for MET-amplified NSCLC patients (pts) who had progressed following EGFR-TKI treatment. FISH was more sensitive than NGS for detecting METamp, and the positive concordance depended on FISH-assessed MET GCN. In pts positive by both methods, savolitinib plus osimertinib significantly improved outcomes."

Next-generation sequencing • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • KIT • MET

Patient-relevant outcomes (PROs) from SACHI: A phase 3 trial of savolitinib (Savo) plus osimertinib (Osi) versus chemotherapy (Chemo) in EGFR-mutant (EGFRm) and MET-amplified (METamp) advanced NSCLC after progression on EGFR-TKIs (ESMO Asia 2025) - P3 | "The improved PROs corresponded with the improved PFS and tumor responses observed with savo-osi in population of EGFRm and METamp advanced NSCLC after progression on EGFR TKIs. These PRO data further support osimertinib plus savolitinib as a new treatment option in this disease setting."

Clinical • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Osimertinib (osi) + savolitinib (savo) in EGFR-mutated (EGFRm) advanced non-small cell lung cancer (NSCLC) with MET overexpression and/or amplification (OverExp/Amp) following progressive disease (PD) on osi: SAVANNAH Asian subset (ESMO Asia 2025) - P2 | "In this subset of Asian pts with EGFRm advanced NSCLC and MET OverExp/Amp from SAVANNAH, osi + savo demonstrated generally consistent efficacy and safety outcomes with the global primary efficacy population, supporting osi + savo as a beneficial oral tx option for Asian pts in this setting. Table: 982P Data cut-off: 23 Aug 2024.*In patients with objective response.BICR, blinded independent central review; CI, confidence interval; DoR, duration of response; NC, not calculable; ORR, objective response rate; PFS, progression-free survival."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

Clinical case report on the efficacy and safety of savolitinib in elderly patients with non-small cell lung cancer harboring METex14 skipping mutations. (PubMed, Transl Cancer Res) - "They were treated with savolitinib as the second-line treatment after previously receiving AP regimens (pemetrexed + cisplatin). The case series demonstrated that savolitinib has a favorable clinical efficacy and safety profile, suggesting its potential as a key therapeutic option for elderly patients with NSCLC harboring METex14 skipping mutations. The treatment offers sustained survival benefits and is well-tolerated."

Journal • Breast Cancer • Cardiovascular • CNS Disorders • Hypertension • Lung Cancer • Movement Disorders • Non Small Cell Lung Cancer • Oncology • Parkinson's Disease • Solid Tumor • MET

A Riskscore Model for Predicting Survival, Tumor Microenvironment, Immunotherapy and Drug Sensitivity of Lung Squamous Cell Carcinoma Based on PI3K/AKT/MTOR Pathway-Related Genes. (PubMed, J Environ Pathol Toxicol Oncol) - "LR group had lower TIDE scores and lower IC50 values (Alpelisib, Ibrutinib, Sapitinib, and Savolitinib). Patients in LR group had potential advantages in survival, immune response, and drug sensitivity. In summary, the results offered new insights into prognosis prediction, immunotherapy, and personalized treatment of LUSC."

Biomarker • Journal • Non Small Cell Lung Cancer • Oncology • Squamous Cell Carcinoma • CAB39 • CDKN1A • TRIB3

Savolitinib Plus Osimertinib in Epidermal Growth Factor-Mutated, MET-Amplified Advanced Non-Small Cell Lung Cancer: A Randomized Phase II trial. (PubMed, Clin Lung Cancer) - P2 | "Savolitinib plus osimertinib demonstrated numerically higher clinical activity versus savolitinib plus placebo in all patients and patients with higher MET biomarker cutoffs."

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

A mismatch in enzyme-redox partnerships underlies divergent cytochrome P450 activities between human hepatocytes and microsomes. (PubMed, Commun Biol) - "Mechanistically, we serendipitously discover that HH CYP3A4-mediated midazolam-metabolism is increased by gefitinib and find that this can only be recapitulated in non-canonical Cytb5R-dependent NADH-HLM and recombinant CYP3A4-Cytb5R. We conclude that Cytb5R is important for HH-CYP3A4 and show HH-consistent CYP3A4-activities in NADH-HLM. Imaging NADH/NADPH in hepatocytes shows equivalent concentrations suggesting CYP redox-partnerships are cofactor-independent and likely influenced by protein-protein interactions as mimicking the dense-intracellular protein using albumin recapitulates HH savolitinib-metabolism in HLM."

Journal • Licensing / partnership • CYB5A • CYP1A2 • CYP3A4

A Concise Review of the Approved MET TKIs (Savolitinib, Gumarontinib, Vebreltinib, Tepotinib, Capmatinib) in China for MET Exon 14 Splice Site Mutated (METex14+) NSCLC Circa 2025. (PubMed, Lung Cancer (Auckl)) - P3 | "Splice site mutations around or within exon 14 of MET (METex14+) are rare, but are one of the common actionable driver mutations in elderly patients with non-small cell lung cancer (NSCLC). On June 30, 2025, vebreltinib has been approved for NSCLC with MET amplification while combination of savoltinib and osimertinib has been approved for EGFR+ post EGFR TKINSCLC with MET amplification post EGFR TKI based on the SACHI trial (NCT05015608). We discuss the current unmet clinical need (need to develop Type II MET TKI to overcome acquired resistance MET mutations at D1228 and Y1230) and future optimal treatment approaches."

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

HUTCHMED Announces Enrollment Completed of SAFFRON Global Phase III Trial of ORPATHYS and TAGRISSO Combination for Certain Lung Cancer Patients with MET Overexpression and/or Amplification After Progression on TAGRISSO (GlobeNewswire) - "The last patient was randomized on October 31, 2025....Topline results from the SAFFRON study are estimated to be reported in the first half of 2026, followed by submission of results for presentation at an appropriate medical congress. If favorable, the results could support global regulatory filings..."

Enrollment closed • P3 data: top line • Non Small Cell Lung Cancer

Savolitinib Registration Studies (GlobeNewswire) - "Recruitment for the SAFFRON global Phase III study for second-line EGFR-mutated NSCLC patients with MET amplification or overexpression is progressing well, with enrollment completion expected in late 2025."

Enrollment status • Non Small Cell Lung Cancer

ctDNA analysis in phase III SACHI trial: Savolitinib (savo) plus osimertinib (osi) versus chemotherapy (chemo) in MET-amplified (METamp) advanced NSCLC after disease progression (PD) on EGFR tyrosine kinase inhibitor (TKI) (ESMO 2025) - P3 | "Background In the phase III SACHI trial (NCT05015608), savo+osi significantly improved PFS versus chemo (pemetrexed + carboplatin/cisplatin) in METamp (by FISH) NSCLC post EGFR-TKI treatment. The preliminary analysis also revealed distinct mechanisms for acquired resistance by savo+osi and chemo treatment. Legal entity responsible for the study The authors."

Circulating tumor DNA • Metastases • P3 data • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Final efficacy data and biomarker analysis from the clear cell cohort of CALYPSO (ESMO 2025) - P2 | "Background CALYPSO is a phase II trial evaluating durvalumab (D), savolitinib (S) and tremelimumab (T) in previously treated advanced renal cell carcinoma (RCC). While response rates for DT were higher than D alone, the predefined requirements were not met. Other endpoints such as OS were not discriminatory compared to D monotherapy."

Biomarker • Clinical • IO biomarker • Tumor mutational burden • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • KIM1 • PD-L1 • TMB

Osimertinib Plus Savolitinib in Patients With EGFR-Mutated Advanced NSCLC With MET Alterations After First-Line Osimertinib: Clinical Outcomes, Safety, and Biomarker Analysis: A Brief Report (J Thorac Oncol) - "Thirty-two patients were enrolled; all had tumors with MET amplification. At primary analysis cutoff (January 2023), confirmed ORR was 47% (80% confidence interval [CI]: 35–60). Median DoR was 14.5 months (95% CI: 5.6–18.7). Median PFS was 7.6 months (95% CI: 3.2–15.9). There was a trend towards increased ORR in patients with high MET gene copy number (≥10 versus <10)."

Biomarker • P2 data • Non Small Cell Lung Cancer

Osimertinib Plus Savolitinib in Patients With EGFR-Mutated Advanced NSCLC With MET Alterations After First-Line Osimertinib: Clinical Outcomes, Safety, and Biomarker Analysis: A Brief Report. (PubMed, J Thorac Oncol) - P2 | "Osimertinib plus savolitinib demonstrated encouraging clinical benefit in patients with EGFR-mutated advanced NSCLC and MET amplification following PD on first-line osimertinib. Safety was consistent with profiles of the individual drugs."

Biomarker • Clinical data • Journal • Infectious Disease • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Pneumonia • Respiratory Diseases • Solid Tumor • EGFR • MET

SAVANNAH: Safety and tolerability of osimertinib (osi) + savolitinib (savo) in EGFRm advanced NSCLC with MET overexpression and/or amplification (OverExp/Amp) following disease progression on osi (ESMO 2025) - P2 | "Conclusions Key AEs were as expected, predominantly grade 1–2 and manageable by dose modification/enhanced toxicity management guidelines (e.g. frequent liver function tests in first 10 wks as risk mitigation for severe liver events; preventive compression stockings for PO). Coupled with demonstrated efficacy benefit and the overall safety profile reported previously, these data support osi + savo as a new oral tx option in this setting."

Clinical • Metastases • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

MET testing and treatment (tx) sequencing after progression on first-line (1L) osimertinib (osi) in patients (pts) with EGFRm advanced NSCLC and acquired MET overexpression and/or amplification (OverExp/Amp): interim analysis of a global real-world (rw) study (ESMO 2025) - P2 | "Background In the phase II SAVANNAH study (NCT03778229), osi 80 mg QD + savolitinib 300 mg BID demonstrated high, clinically meaningful and durable responses in EGFRm advanced NSCLC and MET OverExp/Amp after progression on 1L osi. Conclusions In this global rw analysis, low use of IHC and FISH testing was reported, potentially missing a high number of pts with MET-driven progression on osi. Pts with high MET were more likely to receive targeted tx vs pts with low MET."

Clinical • IO biomarker • Metastases • Real-world • Real-world evidence • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor

ESMO 2025: Final Efficacy Data and Biomarker Analysis from the Clear Cell Cohort of CALYPSO (UroToday) - "The median duration of response with durvalumab was 9.8 months, for durvalumab + tremelimumab was 19.4 months, and for durvalumab + savolitinib was 13.3 months. With a minimum follow-up of 40 months, the response rate for durvalumab was 10%, for durvalumab + tremelimumab was 33% and for durvalumab + savolitinib was 13%....The final progression-free survival analysis showed no difference between the three groups (HR 0.97, 95% CI 0.61-1.55)....The median overall survival for durvalumab was 25.8 months, for durvalumab + tremelimumab was 24.2 months, and for durvalumab + savolitinib was 16.3 months (HR 0.88, 95% CI 0.51-1.51)."

Biomarker • P2 data • Clear Cell Renal Cell Carcinoma

HUTCHMED Highlights Clinical Data to be Presented at the ESMO Congress 2025 (GlobeNewswire) - "Results from the FRUSICA-2 registration study of the fruquintinib and sintilimab combination as a second-line treatment for locally advanced or metastatic renal cell carcinoma will be presented in a Mini Oral session. Additionally, further analyses of the fruquintinib FRUSICA-1 study in endometrial cancer and the savolitinib SACHI and SAVANNAH studies in non-small cell lung cancer will be presented during the poster sessions."

Clinical data • dMMR • Endometrial Cancer • Non Small Cell Lung Cancer • Renal Cell Carcinoma

Identifying Optimal First-Line Treatment Strategy for Advanced-Stage EGFR Mutant NSCLC: A Network Meta-Analysis (IASLC-WCLC 2025) - "Osimertinib and savolitinib achieved the highest ORR (SUCRA=0.9238), while first-generation TKI plus chemotherapy ranked first for disease control rate (SUCRA=0.8226). The safety analysis revealed that second-generation TKI-antibody combination therapy (afatinib plus cetuximab) was associated with the highest incidence of adverse events, evidenced by the maximum SUCRA values for both any-grade AEs (SUCRA=0.8207) and grade 3 or higher AEs (SUCRA=0.8252), while osimertinib plus chemotherapy also showed high incidence of grade 3 or higher AEs (SUCRA=0.7472). Conclusions : For patients with advanced EGFR-mutated NSCLC, osimertinib plus chemotherapy is considered the optimal choice due to its superior efficacy in improving PFS and OS compared with other EGFR-TKI-based treatment strategies. However, the toxicity of third-generation EGFR-TKI plus chemotherapy requires careful attention."

Metastases • Retrospective data • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • EGFR

Prostate Cancer Biomarker Enrichment and Treatment Selection (clinicaltrials.gov) - P2 | N=200 | Active, not recruiting | Sponsor: Canadian Cancer Trials Group | Trial primary completion date: Jun 2025 ➔ Oct 2024

Biomarker • Trial primary completion date • Castration-Resistant Prostate Cancer • Genito-urinary Cancer • Oncology • Prostate Adenocarcinoma • Prostate Cancer • Solid Tumor

A Realworld Study: Clinical Molecular Characteristics and Prognostic Factors of NSCLC With MET Alteration (IASLC-WCLC 2025) - "While MET tyrosine kinase inhibitors (TKIs) like capmatinib and savolitinib are FDA-approved for METex14-altered NSCLC, their efficacy in primary MET-amplified disease remains under investigation...Next-generation MET-TKIs (e.g., savolitinib) show improved efficacy over crizotinib, particularly in METex14-mutated cases. TP53 co-mutations and treatment timing critically influence survival, highlighting the need for biomarker-guided therapeutic strategies. These findings underscore the need for optimized therapeutic strategies in MET-driven NSCLC."

Biomarker • Clinical • IO biomarker • Real-world • Real-world evidence • Fatigue • Hepatology • Liver Failure • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • MET • TP53

Frontline Treatment Duration in MET-Amplified NSCLC After Third-Generation Egfr-TKI Failure: SACHI Study Insights (IASLC-WCLC 2025) - "Methods : We evaluated all screened MET -amplified patients who had been previously treated with third-gen EGFR-TKIs from the SACHI study, which is a randomized, open-label, phase 3 study of savolitinib plus osimertinib versus chemotherapy, targeting MET -amplified advanced NSCLC patients who progressed on first-line EGFR-TKIs...Of these patients, 68 (73.1%) received osimertinib, with a median treatment duration of 12.8 months, while the rest were mainly treated with almonertinib (19.4%) and furmonertinib (6.5%)...Conclusions : NSCLC patients with MET amplification who failed first-line third-gen EGFR TKI treatment demonstrated a high disease burden, affecting their exposure to prior therapy. These data suggested that MET amplification might accelerate disease progression during prior therapy as an early resistance mechanism."

Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • MET