478O - Updated results of oral PD-L1 inhibitor ABSK043 in advanced solid tumor patients (pts) from a phase I study

Background

ICI antibodies have demonstrated promising efficacy across a broad spectrum of tumor types. In a phase I study (NCT04964375), ABSK043, an oral, potent, small-molecule PD-L1 inhibitor, exhibited preliminary efficacy. Here are the first reported data of oral PD-L1 inhibitors in Asian pts, as well as the latest results from this study.

Methods

Pts with advanced solid tumors were dosed with ABSK043 capsules ranging from 200 mg once daily (QD) to 1000 mg twice daily (BID), to evaluate the safety profile and preliminary efficacy. Furthermore assessed were pharmacodynamic (PD) indicators, such as T-cell function and surface PD-L1.

Results

As of the cutoff date (June 7, 2024), 77 pts were enrolled and treated. 87.0% of pts experienced treatment-emergent adverse events (TEAEs), and 29.9% were ≥ Grade 3. The TEAEs ≥15% were anemia (22.1%). No peripheral neuropathy was reported. In all efficacy evaluable pts of pharmacologically active dose groups (600 mg BID, 800 mg BID, and 1000 mg BID), an ORR of 24% (8/34) in the ICI-naïve pts was observed. In the 10 ICI-naïve pts with lung cancer (9 pre-treated and 1 treatment-naïve), the ORR was 40% (4/10). Notably, 3 of 6 (50%) EGFR-mutated and 1 of 2 (50%) KRAS-mutated pts achieved partial response (PR). All three responders with EGFR mutations had PD-L1 TPS ≥ 50% and progressed after at least one line of EGFR TKI therapies, including the 3rd generation. Other responses occurred in five mixed tumor types: MSI-H/dMMR gastric cancer, MSI-H/dMMR endometrial adenocarcinoma, vaginal squamous cell carcinoma, breast cancer (Lynch syndrome), and melanoma. The longest duration of response in the study was 17 months (endometrial adenocarcinoma) and the pt is still on treatment. T cell activation and a dose-dependent decrease in surface PD-L1 expression following ABSK043 treatment were observed in all BID dose groups.

Conclusions

ABSK043 demonstrated a favorable safety profile and impressive anti-tumor activity as a single agent, especially in EGFR-mutated lung cancers with high PD-L1 expression, where monotherapies of ICI antibodies were shown to be ineffective in the past. These findings support a continuing investigation of ABSK043, in EGFR-mutated lung cancers and various other solid tumors.

Clinical trial identification

NCT04964375.

Editorial acknowledgement

Legal entity responsible for the study

Abbisko Therapeutics Co., Ltd., Shanghai, China.

Funding

Abbisko Therapeutics Co., Ltd., Shanghai, China.

Disclosure

All authors have declared no conflicts of interest.