With the release of the abstracts for next week’s annual meeting of the European Society of Medical Oncology (ESMO) late Wednesday, meeting preparation moved into high gear.
Among the most anticipated results that will be presented at the meeting are those from the phase III FLAURA trial of Tagrisso (osimertinib, Astrazeneca plc) as first-line therapy for patients with locally advanced or metastatic non-small-cell lung cancer (NSCLC) who have mutations in the epidermal growth factor receptor (EGFR) kinase, including the resistance mutation T790M.
In July, the company announced that compared to current first-line options Tarceva (erlotinib, Roche Holding AG/Astellas Pharma Inc.) and Iressa (gefitinib, Astrazeneca plc), treatment with Tagrisso resulted in an increase in progression-free survival (PFS) that the company termed “statistically significant and clinically meaningful.” (See BioWorld, July 28, 2017.)
At the time it was released, that news was overshadowed by the failure of the phase III MYSTIC trial, in which the combination of PD-L1 blocker Imfinzi (durvalumab) and CTLA-4 inhibitor tremelimumab (Astrazeneca plc), did not improve PFS compared to platinum-based standard-of-care (SOC) chemotherapy in previously untreated patients with metastatic first-line NSCLC. (See BioWorld, July 28, 2017.)
It looks like, at the ESMO meeting, Astrazeneca will pick itself up and dust itself off both with data from FLAURA, and from the PACIFIC trial, which is testing the effects of Imfinzi after chemoradiation in patients with stage III locally advanced and unresectable NSCLC. The PACIFIC trial, too, has met its endpoint, and according to a report by Medscape, ESMO President-elect Solange Peters has called the full dataset that is to be presented at the meeting “absolutely exciting.”
Results from both the PACIFIC and FLAURA trials will be presented at the Presidential Symposium on Saturday, Sept. 9.
The failure of the Imfinzi/tremelimumab combo has not diminished the cancer world’s appetite for all things immuno-oncology; if anything, it has increased the anticipation for successful combinations, which are widely seen as a critical way to increase response rates.
At the ESMO meeting, the most anticipated of those studies is the melanoma cohort of the phase II ECHO-202 trial looking at indoleamine 2,3-dioxygenase (IDO) inhibitor epacadostat (Incyte Corp.) in combination with PD-1 blocker Keytruda (pembrolizumab, Merck & Co. Inc.).
Like PD-1, IDO1 is an immune modulator. Its activity promotes the generation of regulatory T cells and blocks effector T cells’ activation, enabling tumors to escape from the immune system.
Data for an initial 19 patients were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) meeting in June.
After ESMO abstracts were released, J.P. Morgan’s Cory Kasimov wrote in a note that “overall the results are relatively in line with our expectations and remain quite consistent with both the data from ESMO last year as well as the melanoma cohort of ECHO-204 [epacadostat and Opdivo (nivolumab, Bristol-Myers Squibb Co.)] seen at ASCO this summer. Both the ORR and more importantly the landmark PFS seem to have held up in this larger cohort. . . . In our view, this new dataset, though far from definitive, should lend some added measure of confidence that we might see the same from the pivotal ECHO-301 trial in 1H18.” (See BioWorld Today, June 24, 2016.)
Evercore ISI’s Josh Shimmer was a bit more skeptical. “Given the high response rates seen, it’s entirely predictable that a very good PFS will occur,” he wrote in an analyst note. “The question at hand, however, is whether there are systematic biases in ECHO-202 that lead to enrolling patients who are more responsive to therapy. This could be things like site selection, stage of disease, biopsy findings, etc.”