Orpathys (savolitinib) / AstraZeneca, Hutchmed - LARVOL DELTA

SAVANNAH: Biomarker Concordance and Acquired Resistance in Patients with EGFRm MET-OverExp and / or Amp NSCLC (IASLC-WCLC 2025) - P2 | "MET ctDNA NGS had high specificity but modest sensitivity for MET FISH10+ detection, with further reduced sensitivity when IHC90+ was also considered. Acquired resistance mutation profiles to savolitinib ± osimertinib included known on-target and suspected bypass signalling resistance mechanisms."

Biomarker • Clinical • Discordant • Preclinical • Lung Cancer • Non Small Cell Lung Cancer • Solid Tumor • BRAF • EGFR • ERBB3 • MET

KIM-1 levels in papillary renal cell carcinoma from the CALYPSO trial. (ASCO-GU 2026) - P2 | " Serum KIM-1 concentrations were analyzed in patients with papillary RCC (n=32) and clear cell RCC (n=123) enrolled in a prospective randomized phase II trial evaluating durvalumab plus savolitinib (D+S) for papillary RCC. KIM-1 levels are raised in papillary RCC. They correlated with tumor biology, MET status and response to treatment. Baseline serum KIM-1 levels according to clinical characteristics in papillary and clear cell RCC."

IO biomarker • Tumor mutational burden • Clear Cell Renal Cell Carcinoma • Genito-urinary Cancer • Oncology • Papillary Renal Cell Carcinoma • Renal Cell Carcinoma • Solid Tumor • KIM1 • PD-L1

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 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

Savolitinib plus osimertinib versus chemotherapy for advanced, EGFR mutation-positive, MET-amplified non-small-cell lung cancer in China (SACHI): interim analysis of a multicentre, open-label, phase 3 randomised controlled trial. (PubMed, Lancet) - P3 | "The savolitinib-osimertinib combination improved PFS versus chemotherapy in patients with EGFR mutation-positive, MET-amplified NSCLC that had progressed on EGFR TKI therapy, while maintaining a favourable tolerability profile. This regimen offers a potential oral treatment option for this biomarker-selected population."

Journal • P3 data • P3 data: top line • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR • MET

Real-world outcomes (RWO) of oral MET-inhibition in EGFR MET-amplified (MET-amp) NSCLC (ELCC 2026) - "Treatment regimens included tepotinib (tepo) with osimertinib (Osi) (n=14), capmatinib (Cap) with nazartinib (n=3), savolitinib with Osi (n=1), vebreltinib with Osi (n=1), Cap with Erlotinib/Gefitinib (n=3). MET-treated patients with MET:CEP7 ratio ≥2 (n=10) had similar responses to those with ratio <2 (n=5) (mOS 45.4 vs 49.8m, mPFS on MET-i 8.2 v 6.8m, DOR 8.9 v 6.2m).Conclusions Combination EGFR and MET inhibition benefited both denovo Met-amp and post TKI MET resistant EGFR patients. Oral combinations remain an important option for patients."

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

SAVANNAH: Savolitinib (savo) + osimertinib (osi) in patients (pts) with EGFRm advanced NSCLC and METoverexpression (OverExp) and/or amplification (Amp) following progressive disease (PD) on osi (ELCC 2025) - P2, P3 | "After PD on 1L osi, savo 300 mg BID + osi was well tolerated and demonstrated clinically meaningful and durable response in pts with EGFRm advanced NSCLC with MET IHC 3+/≥90% and/or FISH10+ status. This combination offers a potential treatment option in this setting and is under further investigation in the ongoing Ph 3 SAFFRON study (NCT05261399)."

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

Savolitinib combined with Durvalumab in EGFR wild-type advanced NSCLC patients with MET alterations (SOUND): A multicenter, open-label, Phase II trial (AACR 2026) - "Abstract is embargoed at this time."

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

Final Overall Survival Analysis of S1500: A Randomized, Phase II Study Comparing Sunitinib With Cabozantinib, Crizotinib, and Savolitinib in Advanced Papillary Renal Cell Carcinoma. (PubMed, J Clin Oncol) - P2 | "In conclusion, we observed no significant difference in OS across treatment arms. Although cabozantinib represents a well-supported option for advanced PRCC, the lack of survival benefit underscores the need to develop novel therapies for this disease."

Journal • Metastases • P2 data • Genito-urinary Cancer • Oncology • Renal Cell Carcinoma • Solid Tumor

When EGFR meets MET: Dual blockade as the next post-TKI standard? (PubMed, Med) - "The SACHI trial demonstrated that savolitinib plus osimertinib nearly doubled progression-free survival (PFS) compared with chemotherapy (9.8 vs. 5.4 months; hazard ratio 0.34) in patients with EGFR-mutated, MET-amplified non-small-cell lung cancer (NSCLC) after EGFR tyrosine kinase inhibitor (TKI) failure-the first phase 3 evidence for dual EGFR/MET inhibition in this setting.1."

Journal • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • EGFR

PIONeeR: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (clinicaltrials.gov) - P2 | N=120 | Recruiting | Sponsor: Assistance Publique Hopitaux De Marseille | Not yet recruiting ➔ Recruiting | Trial completion date: Sep 2023 ➔ Feb 2024 | Trial primary completion date: Mar 2023 ➔ Oct 2023

Enrollment open • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • ALK • EGFR • ROS1

PIONeeR: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (clinicaltrials.gov) - P2 | N=120 | Not yet recruiting | Sponsor: Assistance Publique Hopitaux De Marseille

New P2 trial • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • ALK • EGFR • ROS1

PIONeeR: Precision Immuno-Oncology for Advanced Non-small Cell Lung Cancer Patients With PD-1 ICI Resistance (clinicaltrials.gov) - P2 | N=114 | Active, not recruiting | Sponsor: Assistance Publique Hopitaux De Marseille | Recruiting ➔ Active, not recruiting | Trial completion date: Feb 2024 ➔ Feb 2025 | Trial primary completion date: Oct 2023 ➔ Oct 2024

Enrollment closed • Trial completion date • Trial primary completion date • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • ALK • EGFR • ROS1

SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov) - P2 | N=360 | Recruiting | Sponsor: AstraZeneca | Active, not recruiting ➔ Recruiting | Trial completion date: Sep 2022 ➔ Feb 2025 | Trial primary completion date: Sep 2022 ➔ May 2024

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

SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov) - P2 | N=172 | Recruiting | Sponsor: AstraZeneca | Not yet recruiting ➔ Recruiting

Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • MET

SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov) - P2 | N=259 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Apr 2023 ➔ Sep 2022

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

SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov) - P2 | N=259 | Recruiting | Sponsor: AstraZeneca | Trial primary completion date: Feb 2022 ➔ Sep 2022

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

SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov) - P2 | N=192 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

Global commercial progress, delivery of sustainable growth and robust balance sheet (The Manila Times) - "FRUZAQLA (fruquintinib ex-China) in-market sales by Takeda were up 26% to $366.2 million (2024: $290.6m)...ELUNATE (fruquintinib in China) in-market sales were $100.1 million (2024: $115.0m), with strong growth in H2 (H2 up 33% vs. H1)...Total in-market sales, including FRUZAQLA, ELUNATE, SULANDA and ORPATHYS, of $524.7 million achieved growth in 2025 of 5% despite regulatory and commercial headwinds in the first half of 2025....SULANDA revenue was $27.0 million (2024: $49.0m)...ORPATHYS revenue was $18.6 million....TAZVERIK revenue was $2.5 million (2024: $0.9m)..."

Sales • Colorectal Cancer • Epithelioid Sarcoma • Neuroendocrine Tumor • Non Small Cell Lung Cancer • Pancreatic Neuroendocrine Tumor

COST-EFFECTIVENESS ANALYSIS OF SAVOLITINIB-OSIMERTINIB IN ADVANCED NON-SQUAMOUS NSCLC WITH MET AMPLIFICATION FOLLOWING EGFR-TKI RESISTANCE IN CHINA (ISPOR 2026) - "Savolitinib-Osimertinib provides significantly improved survival and is cost-effective versus Ivonescimab plus chemotherapy for EGFR‑TKI-resistant, MET-amplified advanced non-squamous NSCLC in China. Findings are robust across multiple sensitivity and scenario analyses, supporting its inclusion in reimbursement lists to enhance patient access. Methodologically, the study demonstrates an approach to address cross-trial heterogeneity in health technology assessment."

Cost effectiveness • HEOR • Metastases • Lung Cancer • Lung Non-Squamous Non-Small Cell Cancer • Non Small Cell Lung Cancer • Solid Tumor • MET

SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov) - P2 | N=172 | Not yet recruiting | Sponsor: AstraZeneca

New P2 trial • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Thoracic Cancer • MET

SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov) - P2 | N=192 | Recruiting | Sponsor: AstraZeneca | Trial completion date: Jul 2022 ➔ Dec 2022

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

SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov) - P2 | N=366 | Active, not recruiting | Sponsor: AstraZeneca | Recruiting ➔ Active, not recruiting

Enrollment closed • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET

SAVANNAH: Osimertinib Plus Savolitinib in EGFRm+/MET+ NSCLC Following Prior Osimertinib (clinicaltrials.gov) - P2 | N=259 | Recruiting | Sponsor: AstraZeneca | Active, not recruiting ➔ Recruiting | N=192 ➔ 259

Enrollment change • Enrollment open • Lung Cancer • Non Small Cell Lung Cancer • Oncology • Solid Tumor • MET