Tagrisso paired with Hutchmed drug clears lung cancer test

EGFR inhibitors like AstraZeneca’s Tagrisso have been hugely successful in treating EGFR-positive lung cancer, but the durability of treatment is often reduced by resistance mutations. Now, a combination of Tagrisso with another drug looks like it may help tackle that issue.

The most common biomarker among people with EGFR-mutated lung cancer who develop resistance to targeted therapy is MET, and AZ has partnered with China’s Hutchmed to combine its MET inhibitor savolitinib with Tagrisso in clinical trials.

The first phase 2 data on the combination has now come in from the SAVANNAH trial, and is encouraging, prompting the two partners to take the combination into a phase 3 programme.

SAVANNAH tested Tagrisso and savolitinib in patients with EGFR-mutated non-small cell lung cancer (NSCLC), which had progressed on earlier Tagrisso therapy, including a subgroup with high levels of MET over-expression or amplification.

Preliminary results show a 32% overall response rate (ORR) with the combination across the entire study, rising to 49% in the high MET group and falling to 9% in subjects without MET mutations.

The data provide proof of principle for the use of MET-targeting drugs to offset Tagrisso resistance, and charts a way forward towards regulatory approvals of the combination as an alternative to chemotherapy for these patients.

“The results from SAVANNAH suggest savolitinib added to Tagrisso at the time of disease progression could possibly provide these biomarker-selected patients with a potentially less toxic, more effective treatment option,” said AZ’s chief oncology development officer Cristian Massacesi.

Savolitinib has already been approved in China as Orpathys for the treatment of NSCLC patients whose tumours have MET exon 14 skipping mutations who have previously had systemic treatment or are unable to receive chemotherapy.

The drug isn’t yet cleared in the US, where it has been beaten to market by other MET inhibitors, namely Novartis/Incyte’s Tabrecta (capmatinib) and Merck KGaA’s Tepmetko (tepotinib).

Tagrisso, meanwhile, has been FDA-approved as a second-line treatment for EGFR T790M mutation-positive NSCLC since 2015, with its label extended since then to include first-line and adjuvant treatment. It is AZ’s biggest-selling drug, with sales topping $5 billion last year.

The pairing of Tagrisso with savolitinib has now started a phase 3 trial called SAFFRON, which will compare the duo with chemotherapy in EGFR-positive NSCLC with MET mutations, with results due in 2025.

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