- AstraZeneca and Chi-Med's investigational MET inhibitor gave lung cancer patients additional benefit when used in combination with the British pharma's EFGR inhibitor Tagrisso, according to early-stage clinical results presented Sunday at the American Association of Cancer Research annual meeting in Atlanta.
- The study focused on non-small cell lung cancer (NSCLC) patients who were previously treated with an EFGR-targeted therapy like Tagrisso and developed MET-driven resistance to such therapies. Chemotherapy is the primary treatment option for these patients.
- The Phase 1b study supports ongoing Phase 2 work testing the combination in overcoming EFGR resistance following treatment with Tagrisso alone in cases of EFGR-mutated NSCLC. AstraZeneca also stated the trial, dubbed TATTON, will inform the design of a different Phase 2 study, set to explore treatment options to address resistance mechanisms after first-line treatment with Tagrisso.
While the results are from early-stage clinical research, the positive clinical results may encourage the British pharma to carry on with the combo. That could eventually open a new door for patients with this hard-to-treat type of lung cancer — and potentially bolster AstraZeneca's lung cancer business, currently led by Tagrisso (osimertinib).
A type of tyrosine kinase inhibitor (TKI), Tagrisso was AstraZeneca's best-selling cancer product in 2018, with sales nearly doubling from the year prior to total $1.86 billion. A key growth driver last year was gaining a regulatory OK for first-line treatment in EFGR-mutant NSCLC.
AstraZeneca's study of Tagrisso together with the MET inhibitor savolitnib, dubbed TATTON, was aimed at solving a common shortcoming of targeted cancer therapies — acquired resistance. First-line targeted drugs like Tagrisso are broadly effective, but the cancers of some patients can become less susceptible, acquiring resistance mechanisms to initial therapies.
Lecia Sequist, an oncologist at Massachusetts General Hospital and a leader of the TATTON study, attributed the trial's success to its selective patient population in a statement. Patients needed to have documented MET-driven resistance to be enrolled.
"These clinically meaningful responses also demonstrate that as different heterogeneous resistance clones come up, they can in turn be brought under control by tailoring therapy," Sequist said.
The results presented Sunday at AACR were from two relatively small cohorts of TATTON, distinguished by the type of treatment they had previously received.
Among a group of 46 patients treated with a first- or second-generation EFGR TKIs, slightly more than half responded to combination treatment, with 24 partial responses. Median duration of response reached 7.1 months.
The second group, who were previously treated with Tagrisso before developing resistance, fared less well. Twelve of 48 patients saw their tumors partially shrink, yielding a 28% response rate. Median duration of response, however, was nearly 10 months.
Previous research has shown MET amplification to be more common following treatment with third-generation TKIs, present in roughly 25% of patients whose disease progressed. Only 5% to 10% of patients whose disease progressed after receiving first- or second-generation TKIs typically have MET amplification, according to research cited by Sequist.
On the safety side, Sequist noted the combination led to increased toxicity compared to Tagrisso as a montherapy. Nausea, diarrhea and lower numbers of leukocytes and platelets were the most common adverse events observed in the study.