MET is the most common biomarker in cases with EGFR- shifted lung cancer who develop resistance to targeted remedy
Global SAFFRON Phase III trial assessing this combination is underway
primary results from the SAVANNAH Phase II trial showed that Tagrisso( osimertinib) plus savolitinib demonstrated an objective response rate( ORR) of 49( 95 confidence interval( CI), 39- 59) in cases with epidermal growth factor receptor- shifted( EGFRm)non-small cell lung cancer( NSCLC) with high situations of MET overexpression and/ or modification, defined as IHC90 and/ or FISH10, whose complaint progressed on treatment with Tagrisso.
The loftiest ORR was observed in cases with high situations of MET who weren’t treated with previous chemotherapy( 52( 95 CI, 41- 63)). In cases whose tumours didn’t show high situations of MET, the ORR was 9( 95 CI, 4- 18). These results are being participated at the International Association for the Study of Lung Cancer 2022 World Conference on Lung Cancer, taking place 6- 9 August in Vienna, Austria.
Savolitinib, retailed in China under the brand name Orpathys, is an oral, potent, and largely picky MET tyrosine kinase asset( TKI) being concertedly advanced and commercialised by AstraZeneca and HUTCHMED.
While EGFR- targeted remedy can give a durable survival benefit to cases with EGFRm NSCLC, utmost will ultimately develop resistance to their treatment, with MET being the most common resistance biomarker.1 Among cases screened for registration in SAVANNAH, all of whom endured complaint progression on Tagrisso, 62 had tumours with MET overexpression and/ or modification, and further than one- third( 34) met the defined high MET position cut- off.
Myung- Ju Ahn, MD, PhD, Professor of Hemato- Oncology at the Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea, and star Investigator in the SAVANNAH Phase II trial, said “ Acquired resistance to targeted remedy and complaint progression are delicate realities for utmost cases with EGFR- shiftednon-small cell lung cancer. These primary SAVANNAH results potentially support a new approach for relating cases with MET overexpression and/ or modification who are most likely to profit from a MET- directed remedy, like savolitinib. They also suggest that with the right biomarker testing strategy, MET may be a further current target among resistant cases than preliminarily understood, supporting farther disquisition of the osimertinib plus savolitinib authority. ”
Cristian Massacesi, Chief Medical Officer and Oncology Chief Development Officer, AstraZeneca, said “ The current standard of care for cases with EGFR- shifted lung cancer who progress on targeted treatment is chemotherapy. The results from SAVANNAH suggest savolitinib added to Tagrisso at the time of complaint progression could conceivably give these biomarker- named cases with a potentially less poisonous, more effective treatment option. We look forward to better understanding the eventuality of the Tagrisso plus savolitinib authority in this trial and in the SAFFRON Phase III trial. ”
Weiguo Su, Chief Executive Officer and Chief Scientific Officer, HUTCHMED, said “ It’s encouraging to see the savolitinib and Tagrisso combination authority progress into a global Phase III study, SAFFRON, with a well- supported case selection strategy that could profit further cases than preliminarily honored. The primary results of the SAVANNAH study also affirm the part of molecular testing previous to initiating posterior treatment fornon-small cell lung cancer cases who witness complaint progression on an EGFR- targeted remedy. We’re aligned in pursuing a picky, patient- centric approach in development sweats for savolitinib in this setting. ”
In this analysis, cases ’ MET overexpression and/ or modification situations were determined by two tests immunohistochemistry( IHC), which detects if cancer cells have a particular protein or marker on their face, and luminescence in situ hybridisation( FISH), which detects a specific DNA sequence from cancer cells. All cases in this analysis( n = 193) had at least IHC50 and/ or FISH5, and were treated with savolitinib 300 mg formerly daily added to Tagrisso 80 mg formerly daily following complaint progression on Tagrisso alone.
Summary of efficacity resultsi
All cases( IHC50 and/ or FISH5; n = 193)
Cases with high situations of METii
IHC90 and/ or FISH10)
Cases with lower situations of METii( n = 77)
n = 108)
No previous chemo( n = 87)
ORR,( 95 CI)
32( 26, 39)
49( 39, 59)
52( 41, 63)
9( 4, 18)
Median DoRiii, months( 95 CI)
months( 95 CI)
DCRv,( 95 CI)
61( 53, 68)
74( 65, 82)
75( 64, 83)
43( 32, 55)
Analysis data cut- off 27 August 2021
ii. Eight cases barred from group analyses due to invalid or missing test results
iii. DoR, duration of response
iv. PFS, progression-free survival
v. DCR, complaint control rate
The safety profile of Tagrisso plus savolitinib was harmonious with the known biographies of the combination and each treatment alone. No new safety signals were linked. lower than half( 45) of cases in this analysis endured Grade 3 or advanced adverse events( AEs), with those most constantly reported including pulmonary embolism, dyspnoea, dropped neutrophil count and pneumonia. AEs attributable to savolitinib and leading to termination passed in 13 of cases.
The global SAFFRON Phase III trial will further assess the Tagrisso plus savolitinib combination versus platinum- grounded fellow chemotherapy in cases with EGFRm, MET- overexpressed and/ or amplified, locally advanced or metastatic NSCLC following Tagrisso. Cases are being prospectively named using the high MET position cut- off linked in SAVANNAH.
AstraZeneca( LSE/ STO/ Nasdaq AZN) is a global, wisdom- led biopharmaceutical company that focuses on the discovery, development, and commercialisation of tradition drugs in Oncology, Rare conditions, and BioPharmaceuticals, including Cardiovascular, Renal & Metabolism, and Respiratory & Immunology. Grounded in Cambridge, UK, AstraZeneca operates in over 100 countries and its innovative drugs are used by millions of cases worldwide.