Abstract 1329P
Background
HA121-28 is a highly potent, multi-targeted tyrosine kinase inhibitor with RET as its main target. We present our data on the efficacy, safety and pharmacokinetics (PK) of HA121-28 in patients (pts) with advanced solid tumors.
Methods
Adult pts (ECOG ≤ 1) with histologically/cytologically confirmed advanced/metastatic solid tumor (unresectable) that has progressed on/ not responded to/ intolerant to the standard therapy were recruited. This study consisted of two parts: (1) the dose-escalation part and (2) the dose-expansion part. In part 1, a "3+3" dose escalation was employed, starting from 25 mg once a day (qd). In part 2, pts received the selected dosing regimen based on data from part 1. The primary endpoints were the determinations of maximum tolerated dose (MTD), PK and safety. The secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DoR) as per RECIST 1.1.
Results
As of Apr. 28, 2021, 41 eligible pts (18 males) with a median age of 51 (range, 29-76) were enrolled. Part 1 included 29 pts. Two dose-limiting toxicities (grade-3 anorexia; prolonged QTc interval) occurred at 800 mg. 600 mg qd was set as MTD and chosen as the recommended part 2 dose. 12 pts were enrolled in part 2, including 11 pts with RET fusion+ non–small cell lung cancer (NSCLC). Treatment-related adverse events (TRAEs) of any grade occurred in 38 (93%) of 41 pts, 6 (15%) were ≥ grade 3. The most common TRAEs were rash (49%), diarrhea (41%), prolonged QTc interval (37%), proteinuria (20%), and nausea (20%). The exposure of HA121-28 increased dose-dependently within the dose range of 25-800 mg. Among 17 pts (8 males), median age 49 (range 40-71) with RET fusion+ NSCLC (2 with 450 mg, 13 with 600 mg, 2 with 800 mg), 11 (64%) had been heavily pretreated (≥ 2 prior lines). One responder has received 10 months of treatment and was still ongoing at the time of analysis. The ORR of RET fusion+ NSCLC pts was 41% (95% CI: 18-67%, 7 PRs) and DCR was 82% (95% CI: 56-96%, 7 SDs) by investigators. Objective response was not observed in pts with other types of tumors. Median PFS and DoR were not reached.
Conclusions
HA121-28 showed a tolerable safety profile with encouraging efficacy among RET fusion+ NSCLC pts.
Clinical trial identification
NCT03994484.
Editorial acknowledgement
Legal entity responsible for the study
CSPC Zhongqi Pharmaceutical Technology Co., Ltd.
Funding
CSPC Zhongqi Pharmaceutical Technology Co., Ltd.
Disclosure
All authors have declared no conflicts of interest.