Phase Ib/II Study of Enzalutamide with Samotolisib (LY3023414) or Placebo in Patients with Metastatic Castration-Resistant Prostate Cancer
Purpose: To report effectiveness and safety of samotolisib (LY3023414 PI3K/mTOR dual kinase and DNA-dependent protein kinase inhibitor) plus enzalutamide in patients with metastatic castration-resistant cancer of the prostate (mCRPC) following cancer progression on abiraterone.
Patients and techniques: Within this double-blind, placebo-controlled phase Ib/II study (NCT02407054), carrying out a lead-in segment for evaluating safety and pharmacokinetics of samotolisib and enzalutamide combination, patients with advanced castration-resistant cancer of the prostate with progression on prior abiraterone were randomized to get enzalutamide (160 mg daily)/samotolisib (200 mg two times daily) or placebo. Primary endpoint was progression-free survival (PFS) assessed by Cancer Of The Prostate Numerous Studies Working Group criteria (PCWG2). Secondary and exploratory endpoints incorporated radiographic PFS (rPFS) and biomarkers, correspondingly. Log-rank tests assessed treatment group variations.
Results: Overall, 13 and 129 patients were signed up for phase Ib and II, correspondingly. Dose-restricting toxicity wasn’t reported in patients during phase Ib and mean samotolisib exposures continued to be within the targeted range despite a 35% decrease when administered with Samotolisib enzalutamide. In phase II, median PCWG2-PFS and rPFS was considerably longer within the samotolisib/enzalutamide versus placebo/enzalutamide arm (3.8 versus. 2.8 several weeks P = .003 and 10.2 versus. 5.5 several weeks P = .03), correspondingly. Patients without androgen receptor splice variant 7 demonstrated a substantial and clinically significant rPFS benefit within the samotolisib/enzalutamide versus placebo/enzalutamide arm (13.2 several weeks versus. 5.3 several weeks P = .03).
Conclusions: Samotolisib/enzalutamide has tolerable negative effects and considerably improved PFS in patients with mCRPC with cancer progression on abiraterone, and this can be filled with patients with PTEN intact with no androgen receptor splice variant 7.