651P - Phase I study of XNW27011, a novel claudin 18.2 ADC, in patients with locally advanced and/or metastatic solid tumors

Background

XNW27011 is a novel claudin 18.2(CLDN 18.2)-targeting ADC with the TMALIN® linker, a proprietary TOP1i payload more potent than Dxd, and homogeneous DAR of 8. Here we report the preliminary results from the dose escalation phase of the first in human, multi-center, open-label, phase I/II study of XNW27011 in patients (pts) with locally advanced and/or metastatic solid tumors who have failed or are intolerant to standard therapies.

Methods

XNW27011 was given starting from 0.6 mg/kg (Q3W, IV) in an accelerated titration followed by 3+3 escalation scheme. The primary objective of dose escalation phase was to determine MTD.

Results

As of Apr. 15, 2024, 16 pts were enrolled in 6 dose cohorts from 0.6 to 6.0 mg/kg, including 11 GC/GEJC, 2 OC, 2 PC, and 1 duodenal periampullary adenocarcinoma (ECOG 0-1, majority of pts received ≥3 lines of prior therapy). 12 pts had various levels of CLDN18.2-expression (≥1%, IHC ≥ 1+). During DLT period, the most common AEs were nausea and vomiting, followed by white blood cell decrease, neutrophil decrease and anemia. No ≥ grade 3 TRAEs were observed below 4.8 mg/kg during DLT period. No ILD or MMAE-related ocular AEs and peripheral neuropathy were observed. One patient experienced DLT at 6.0 mg/kg. The table summarized efficacy in 14 evaluable pts. Efficacy was observed even at doses as low as 0.6 mg/kg. Prior PD-1 immunotherapy, irinotecan or CLDN18.2 antibody therapy seemed not to impact efficacy. Table: 651P

Efficacy outcomes

*CLDN18.2+: any level of CLDN18.2 expression, defined as CLDN 18.2 _1%, IHC_1+; GC/GEJC¹: gastric cancer/gastroesophageal junction cancer; OC²: ovarian cancer; PC³: pancreatic cancer

XNW27011 has shown similar concentration-time curves of ADC and TAb, long T_1/2= 5-9 days, and extremely low free payload at all tested doses (C_max of 0.253 to 1.65 ng/mL corresponding to 0.6-6.0 mg/kg doses).

Conclusions

XNW27011 demonstrated a favorable safety profile with large therapeutic window, superior preliminary efficacy across tumor type and CLDN 18.2 expression level, and excellent PK properties including low payload plasma exposure. The study is ongoing with the expansion phase being initiated in multiple tumor cohorts.

Clinical trial identification

Editorial acknowledgement

Xiujing Emma Feng from Evopoint Biosciences USA, Inc.

Legal entity responsible for the study

Evopoint Biosciences Co. Ltd.

Funding

Evopoint Biosciences Co. Ltd.

Disclosure

H. Zhao, Y. Hu, H. Wei, Y. Zhao, Y. Wang, Q. Shi, J. Li: Financial Interests, Personal, Full or part-time Employment: Evopoint Biosciences Co. Ltd.; Financial Interests, Personal, Stocks/Shares: Evopoint Biosciences Co. Ltd. All other authors have declared no conflicts of interest.