DLT, MTD, and RP2D
cardiotoxicity, ocular toxicity
INTERSTITIAL PNEUMONIA
In the escalation phase, patients were enrolled into 10 cohorts (0.5–18 mg BID), no DLT were observed, and MTD was not reached. Nine milligrams and above dose can achieve the target exposure, the 15 mg and above dose group had increased safety risks, with drug-related AE leading to discontinuation (cardiotoxicity, ocular toxicity, and interstitial pneumonia), whereas the 12 mg dose group had no drug-related AE leading to discontinuation. As the dose of HL-085 increased, clinical efficacy began to be observed. No subjects achieved PR in the 6 mg dose and below group, while patients achieved PR in the 9 mg and above dose group. The confirmed ORR was 14.3% in all dose groups which was as high as 26.7% in the 12 mg dose group. Based on the available safety, efficacy, pharmacokinetic analysis, and pharmacodynamic analysis, 12 mg BID was identified as the RP2D and selected for dose expansion.