Deciphera Pharmaceuticals has posted data from a phase 1 trial of its small molecule switch control inhibitor of CSF1R, DCC-3014. The early-phase data have emboldened Deciphera to expand the trial to include patients with tenosynovial giant cell tumors (TGCTs).
DCC-3014 is designed to selectively bind to the switch pocket in CSF1R over other human kinases. CSF1R influences the function of macrophages, including those that tumors induce to suppress the immune response. As such, Deciphera thinks DCC-3014 can counter these mechanisms and thereby improve outcomes in cancers in which tumor associated macrophages are implicated.
Deciphera moved DCC-3014 into a phase 1 trial in patients with advanced malignancies on the back of data from a preclinical colorectal cancer model. Now, the Massachusetts-based biotech has shared an early look at the clinical data that could start to vindicate its decision to invest in DCC-3014.
The phase 1 trial had assessed five dose cohorts of DCC-3014 across 24 patients as of the Nov. 9 cutoff. The data show “material reductions” in CSF1R-positive macrophages in the blood, giving Deciphera encouragement that the mechanism of DCC-3014 works as envisaged. Deciphera has also generated pharmacokinetic data it thinks support twice-weekly maintenance dosing.
On the safety front, Deciphera is yet to see dose-limiting toxicities among the participants who took twice-weekly maintenance doses. No grade 3 or 4 treatment emergent adverse events have affected more than 10% of the patients in the twice-weekly dosing cohorts.
The cohort of patients who received 10 mg of DCC-3014 did feature dose-limiting toxicities, though. Two of the seven patients in the cohort experienced clinically asymptomatic laboratory values that the study recorded as dose-limiting toxicities.
Deciphera thinks the early data justify further development of DCC-3014. Enrollment in the phase 1 trial in advanced malignancies is ongoing. In parallel, Deciphera is gearing up to expand the study to include patients with TGCTs, benign, recurring tumors that can damage surrounding tissues as they grow. Deciphera thinks DCC-3014 can provide an alternative to the surgical removal of TGCTs.