A Phase Ib/II Study Confirmed Inhibition of Autophagy Synergizes Anti-tumor Effect of High Dose CDK4/6i

Summary

In order to explore the safety and antitumor efficacy of different doses of CDK4/6 inhibitor Palbociclib in combination with the autophagy inhibitor hydroxychloroquine (HCQ) , a phase Ib/II study was conducted. This study will adopt a 3+3 design and include three predefined dose groups of palbociclib: 100mg QD, 150mg QD, and 200mg QD. Initially, 600mg bid dose of hydroxychloroquine group will be administered in combination. The trial will use the first cycle (28 days) as the observation period for tolerability, observing and evaluating the occurrence of DLTs after medication and determining the maximum tolerated dose/maximum administered dose (MTD/MAD) and recommended phase 2 dose (RP2D) of the combination therapy. This study improves the efficacy of CDK4/6 inhibitors in the treatment of solid tumors by reversing DTP status through the use of HCQ.

Timeline

Start

2023-11-07

Primary completion

2024-05-07

Completion

2024-12-31

Publications

• Gong C, Lin Q, Qin T, Zeng Y, Xu F, Yang Y, Yin D, Duan Z, Chen CL, Wing-Cheong Chow L, Liu Q, Hamai A, Mehrpour M, Lin Q, Li J, Song E. Targeting autophagy plus high-dose CDK4/6 inhibitors in advanced HR+HER2- breast cancer: A phase 1b/2 trial. Med. 2025 May 9;6(5):100559. doi: 10.1016/j.medj.2024.11.012. Epub 2024 Dec 27.

Drugs

Indications

No indication recorded.