A Phase I Dose-Escalation and Dose-Expansion Study of FCN-437c, a Novel CDK4/6 Inhibitor, in Patients with Advanced Solid Tumors

A phase I study evaluated the safety, tolerability, and maximum-tolerated dose (MTD)/recommended phase II dose (RP2D) of FCN-437c, a novel, orally available cyclin-dependent kinase inhibitor (CDK4/6i), in participants with advanced/metastatic solid tumors (aSTs). FCN-437c was escalated from 50 mg (once daily [QD] on days 1–21 of 28-day cycles) to the MTD/RP2D. In the dose-expansion phase, patients with CDK4/6i-treated breast cancer, or KRAS-mutant (KRAS^mut) non-small-cell lung cancer (NSCLC) received the MTD. Twenty-two patients were enrolled. The most common tumors in the dose-escalation phase (n = 15) were breast, colorectal, and lung (each n = 4 [27.3%]). The dose-expansion phase included five (71.4%) patients with breast cancer and two (28.6%) with KRAS^mut NSCLC. Twenty (90.9%) participants experienced FCN-437c–related adverse events. Dose-limiting toxicities occurred in two (33.3%) participants (200-mg dose, dose-escalation phase): grade 3 neutropenia and grade 4 neutrophil count decreased. Due to toxicities reported at 150 mg QD, the MTD was de-escalated to 100 mg QD. One (4.5%) participant (KRAS^mut NSCLC, 100-mg dose) achieved a partial response lasting 724+ days, and five (22.7%) had stable disease lasting 56+ days. In conclusion, FCN-437c was well tolerated with encouraging signs of antitumor activity and disease control. Further exploration of FCN-437c in aSTs is warranted.