As Europe’s premier cancer conference ESMO gets underway in Germany with a raft of new immuno-oncology studies, Deciphera has new data that shows there’s still plenty to talk about when it comes to kinase inhibitors.
Earlier this year at ASCO, Deciphera reported phase 1 data with KIT/PDGFRα-targeted kinase inhibitor DCC-2618 in resistant gastrointestinal stromal tumors (GIST) that sparked a big increase in the biotech’s share price and helped it to raise $170 million in a follow-on offering just a few months after a $128 million IPO.
Shares have fallen back almost to pre-ASCO levels in the interim, but the Waltham, Massachusetts-based biotech is back at ESMO with updated results on response rates and progression-free survival (PFS) that—according to CEO Mike Taylor, Ph.D.—look better than the results seen in registration trials for approved kinase inhibitors for GIST, such as Pfizer’s Sutent (sunitinib) and Bayer’s Stivarga (regorafenib).
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Three-month data from the study show disease control rates of 81% with DCC-2618 as second- and third-line GIST therapy, and 66% in fourth-line patients, with overall response rates of 21% and 9%, respectively. The same pattern was seen with median PFS, coming in at 42 weeks for second-line patients, 40 weeks in third-line, and 24 for the fourth-line group.
The data “demonstrate the potential of DCC-2618 to provide improved, durable clinical benefit for GIST patients from second-line through fourth-line plus,” said Taylor in a release.
At the moment, Novartis’ Glivec (imatinib) or an equivalent generic is generally the first-line treatment choice, with Sutent and Stivarga approved for later-line use, but the effects of all these drugs tend to be limited due to the development of resistance mutations.
Deciphera has an ongoing phase 3 study of DCC-2618 as a once-daily, fourth-line GIST therapy—called INVICTUS—that is due to read out next year, and it is also planning a second pivotal trial (INTRIGUE) later this year that will pit its drug against Sutent as a second-line treatment.
The company says its initial objective is to get regulatory approval of DCC-2618 as a “late-line” therapy for GIST after Gleevec, Sutent and Stivarga—serving a patient group with no approved therapies—moving to second line post-Gleevec and eventually to a first-line indication. Meanwhile, it's enrolling patients in a series of phase 1 studies in other diseases involving KIT/PDGFRα abnormalities, including systemic mastocytosis and brain cancer (glioma/glioblastoma multiforme).
Deciphera isn’t the only company developing a KIT/PDGFRα inhibitor, and its closest rival in that regard is Blueprint Medicines with its candidate avaprinitib (BLU-285) in phase 1 testing for GIST. The biotech claims DCC-2618 has the edge, however, thanks to a broader inhibition profile across clinically relevant KIT mutations and a favorable safety profile. Dose reductions and discontinuations were “relatively few” in the phase 1 trial, it says, at 14% and 11%, respectively.
Shares in Deciphera fell around 18% after the ESMO presentation, which was an "overreaction...to a data set that is still maturing," according to Konstantinos Aprilakis, M.D., an analyst at JMP Securities. He says a reduction in ORR in second-line patients versus the ASCO presentation—which seemed to spook investors—resulted from an influx of newly-enrolled patients with data not mature enough to assess for best response.