A phase II study of efficacy and safety of RC48-ADC in patients with locally advanced or metastatic HER2-overexpressing gastric or gastroesophageal junction cancers.
Zhi Peng, Tianshu Liu, Jia Wei, Airong Wang, Yifu He, Liuzhong Yang, Xizhi Zhang, Nanfeng Fan, Suxia Luo, Jifang Gong, Zhen Li, Kangsheng Gu, Jin Lü, Jianming Xu, Qingxia Fan, Rui‐Hua Xu, Liangming Zhang, Jianmin Fang, Yi Ba, Lin Shen
Abstract
4560 Background: RC48-ADC is an antibody-drug conjugate (ADC) drug comprised of a novel humanized anti-HER2 IgG1, a linker, and a microtubule inhibitor, MMAE. The MoA included inhibition of HER2 signal pathway and cytotoxicity of MMAE. RC48-ADC has demonstrated promising anti-tumor activity in pre-clinical and early clinical studies. The current study is designed to evaluate the efficacy and safety of RC48-ADC in heavily treated patients with HER2-overexpressing (IHC 2+ or 3+) gastric or gastro-esophageal junction cancers. Methods: This is an open-label, multicenter, single-arm, phase II study. Eligibility criteria include: histologically confirmed gastric or gastro-esophageal junction cancers, HER2-overexpression (IHC 2+ or 3+), ECOG PS 0-1, post-to ≥2 prior systemic treatment. The patients received RC48-ADC, 2.5 mg/kg, q2w until disease progression, unacceptable toxicity, withdrawal, or study termination. The primary endpoint was ORR. PFS, OS, and safety were also evaluated. Results: Patient enrollment started in July 2017, and completed in November 2019. By the data cut-off date on 17-Dec-2019, 127 patients were enrolled. The median age was 58 years. At baseline, 59 patients (46.5%) had received ≥ 3 lines prior treatment. For the overall 127 patients, the investigator-assessed confirmed ORR was 18.1% (95% CI: 11.8%, 25.9%). Sub-group ORR was 19.4% and 16.9% for the patients post to 2 lines and ≥ 3 lines, respectively. For the 111 patients who were monitored for ≥ 2 cycles of efficacy assessments (i.e. 12 weeks), the ORR was 20.7% (95% CI: 13.6%, 29.5%). For the 127 patients, the mPFS was 3.8 months (95% CI: 2.7, 4.0, 89 events [70.1%]) and the mOS was 7.6 months (95% CI: 6.6, 9.2, 52 events [40.9%]). The most commonly reported treatment-related AEs were leukopenia (52.0%), alopecia (51.2%), neutropenia (48.0%), and fatigue (42.5%). Conclusions: RC48-ADC demonstrated a clinically meaningful response and survival benefit in the heavily treated patients with HER2-overexpressing gastric or gastro-esophageal junction cancers. The safety profile was in line with the previously reported data of RC48-ADC. RC48-ADC showed positive benefit/risk ratio for the target population. Clinical trial information: NCT03556345 .