Ignyta has taken another step toward approval of entrectinib and a showdown with Pfizer. The TRK tyrosine kinase inhibitor (TKI) achieved (PDF) a median duration of response (DOR) of 28.6 months at the latest interim review, suggesting its effect may last longer than that of the incumbent.
The limitations of cross-trial comparisons make it impossible to say exactly how Ignyta’s entrectinib matches up to Pfizer’s Xalkori, the current go-to drug for ROS1-positive NSCLC patients. But, in the context of the 32-patient, single-arm study in which it is being tested, entrectinib is doing a decent job of painting itself as a viable contender for the crown.
At the last count, median DOR and progression-free survival (PFS) stood at 28.6 and 29.6 months, respectively. Both numbers have increased considerably since Ignyta presented data in April. Back then, DOR and PFS clocked in at 17.2 months and 19.1 months, respectively. More than half of the enrolled patients are still in the study.
The latest figures compare favorably to those generated by Xalkori during its path to market. Such comparisons always come with an asterisk noting their limitations. But the data have nonetheless emboldened Ignyta CEO Jonathan Lim, M.D. to paint entrectinib as more than just a drug patients take after Xalkori fails them.
“We believe that entrectinib has the potential to be a best-in-class therapeutic option as a first-line targeted therapy for patients with ROS1-positive NSCLC,” Lim said in a statement. “The extended duration of response and progression-free survival times observed in these interim data are particularly compelling, and we believe may be driven by entrectinib’s CNS activity.”
That CNS activity stems from entrectinib’s ability to cross the blood-brain barrier. Brain metastases are fairly common in NSCLC patients—11 of the 32 subjects in Ignyta’s trial had CNS disease at baseline—and as such drugs that treat tumors at both sites are desirable. Among the six patients with measurable lesions in the Ignyta trial, five experienced objective intracranial responses after treatment with entrectinib.
Ignyta is gearing up to pitch the data to regulators. The San Diego, California-based biotech plans to file dual NDAs covering the use of entrectinib in ROS1-positive NSCLC and NTKR-positive solid tumors next year.
Guiding entrectinib through the regulatory process would position Ignyta to compete with Pfizer for the 1% to 2% of NSCLC patients who have ROS1 arrangements. Entrectinib’s potential trump cards are its potency—which tops that of Xalkori in preclinical models—and its ability to cross the blood-brain barrier to treat CNS metastases.
Pfizer has recognized the limitations of Xalkori and has designed a drug to address them, lorlatinib. Phase 2 data presented this week linked lorlatinib to an intracranial objective response rate of 56% of ROS1-positive NSCLC patients. That trial enrolled pretreated patients. Ignyta’s is limited to ROS1 inhibitor-naïve patients.