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Poster session 01

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

Date

14 Sep 2024

Session

Poster session 01

Topics

Clinical Research;  Targeted Therapy

Tumour Site

Ovarian Cancer;  Gastric Cancer;  Pancreatic Adenocarcinoma;  Gastro-Oesophageal Junction Cancer

Presenters

Jinming Yu

Citation

Annals of Oncology (2024) 35 (suppl_2): S482-S535. 10.1016/annonc/annonc1589

Authors

J. Yu1, Y. Sun1, T. Liu2, S.G. Gao3, Z. Guo4, X. Liang5, F. Ning6, M. Zhang7, Y. Zhang8, N. Zhang9, X. Wang10, H. Zhao11, Y. Hu12, H. Wei13, Y. Zhao14, Y. Wang14, Q. Shi15, J. Li16

Author affiliations

  • 1 Phase I Clinical Trial Center, Affiliated Hospital of Shandong First Medical University, 250117 - Jinan/CN
  • 2 Medical Oncology Department, Zhongshan Hospital, Fudan University, 200032 - Shanghai/CN
  • 3 Oncology Department, The First Affiliated Hospital Of Henan University of Science &Technology, Luoyang City/CN
  • 4 Special Need Ward, Fujian Cancer Hospital, 350014 - Fuzhou/CN
  • 5 Phase I Ward, HuBei Cancer Hospital, 430072 - Wuhan/CN
  • 6 Oncology Department, Binzhou Medical University Hospital, 264003 - Yantai/CN
  • 7 Oncology Department, The Second Hospital of Anhui Medical University, 230032 - Hefei/CN
  • 8 Oncology Department, Cancer Hospital Affiliated to Harbin Medical University, 150084 - Harbin/CN
  • 9 Department Of Gastroenterology, Shanxi Cancer Hospital, 030313 - Taiyuan/CN
  • 10 Clinical Trial Center, Shanxi Cancer Hospital, 030013 - Taiyuan/CN
  • 11 Clinical Development Department, Evopoint Biosciences Co. Ltd., 610000 - Chengdu/CN
  • 12 Department Of Medicinal Chemistry, Evopoint Biosciences, Co. Ltd., 215000 - Suzhou/CN
  • 13 Department Of Biology, Evopoint Biosciences, Co. Ltd., 215000 - Suzhou/CN
  • 14 Clinical Development Department, Evopoint Biosciences, Co. Ltd., 215000 - Suzhou/CN
  • 15 Department Of Clinical Pharmacology, Evopoint Biosciences Co. Ltd., 610000 - Chengdu/CN
  • 16 Department Of Clinical Pharmacology, Evopoint Biosciences USA Inc., 01742 - Concord/US

Resources

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Abstract 651P

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

All tumor (n=14) CLDN18.2+ * tumor (n=11) CLDN18.2+ * GC/GEJC 1 (n=8) CLDN18.2+ * OC 2 (n=2) CLDN18.2+ * PC 3 (n=1)
ORR 50% (7/14) 64% (7/11) 63% (5/8) 50% (1/2) 100% (1/1)
DCR 86% (12/14) 100% (11/11) 100% (8/8) 100% (2/2) 100% (1/1)

*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 T1/2= 5-9 days, and extremely low free payload at all tested doses (Cmax 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.

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