Clinical Trial Update

Hutchmed & AstraZeneca Initiate SANOVO Phase III Study Of Orpathys In Combo With Tagrisso To Treat Certain NSCLC Patients In China

September 13,2021 09:32 AM
- By Admin

Hutchmed and AstraZeneca have initiated SANOVO, a China phase III study of Orpathys (savolitinib), an oral, potent, and highly selective MET tyrosine kinase inhibitor (TKI), in combination with AstraZeneca’s third-generation, irreversible epidermal growth factor receptor (EGFR) TKI, Tagrisso (osimertinib) as a first-line treatment in certain non-small cell lung cancer (NSCLC) patients whose tumors harbor EGFR mutation and overexpress MET.

The phase III trial is a blinded, randomized, controlled study in previously untreated patients with locally advanced or metastatic NSCLC with activating EGFR mutations and MET overexpression. The study will evaluate the efficacy and safety of Tagrisso in combination with Orpathys comparing to Tagrisso alone, a standard-of-care treatment option for these patients. The primary endpoint of the study is median progression free survival (PFS) as assessed by investigators. Other endpoints include median PFS assessed by an independent review committee, median overall survival (OS), objective response rate (ORR), duration of response (DoR), disease control rate (DCR), time to response (TTR), and safety.

Lung cancer is the leading cause of cancer death among men and women, accounting for about one-fifth of all cancer deaths. More than a third of the world’s lung cancer patients are in China. Lung cancer is broadly split into NSCLC and small cell lung cancer, with 80-85% classified as NSCLC.

MET is a tyrosine kinase receptor.11 Aberration of MET (amplification or overexpression) is present in both treatment naïve patients as well as being one of the primary mechanisms of acquired resistance to EGFR TKIs for metastatic EGFR-mutated NSCLC.

Savolitinib is an oral, potent, and highly selective MET TKI that has demonstrated clinical activity in advanced solid tumors. It blocks atypical activation of the MET receptor tyrosine kinase pathway that occurs because of mutations (such as exon 14 skipping alterations or other point mutations) or gene amplification.

Tagrisso is a third-generation, irreversible EGFR TKI with clinical activity against central nervous system metastases. Tagrisso (40mg and 80mg once-daily oral tablets) has been used to treat more than 325,000 patients across indications worldwide and AstraZeneca continues to explore Tagrisso as a treatment for patients across multiple stages of EGFR-mutated NSCLC.

In phase III trials, Tagrisso is being tested in the neoadjuvant resectable setting (NeoADAURA), in the Stage III locally advanced unresectable setting (LAURA) and, in combination with chemotherapy, in the Stage III locally advanced or Stage IV metastatic settings (FLAURA2). AstraZeneca is also researching ways to address tumor mechanisms of resistance through the SACHI and SANOVO phase III trials, as well as the SAVANNAH and ORCHARD phase II trials, which test Tagrisso given concomitantly with savolitinib, as well as other potential new medicines.