A phase 1 dose escalation/expansion study of GSK5764227 (GSK’227), a B7-homolog 3 (B7-H3) protein targeted antibody-drug conjugate (ADC), in patients with advanced solid tumors, including gastrointestinal (GI) cancers.
GSK5764227（GSK’227）——一种靶向B7同源物3（B7-H3）蛋白的抗体-药物偶联物（ADC）——在晚期实体瘤（包括胃肠道癌症）患者中的1期剂量递增/扩展研究
📄 英文摘要 English Abstract
TPS847
Background:
B7-H3 is an immune checkpoint protein overexpressed in multiple solid tumors with limited expression in normal tissues. GSK’227 (HS-20093), a novel B7-H3-targeted ADC, is composed of a human anti–B7-H3 monoclonal antibody linked to a topoisomerase I inhibitor via a protease-cleavable linker, and has shown acceptable safety and promising antitumor activity in patients of Asian origin with advanced solid tumors (NCT05276609; NCT05830123). The current study will evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of GSK’227 in patients with solid tumors, including GI cancers, in a global population.
Methods:
This two-part (dose-escalation [1a] and expansion [1b]) global, open-label, Phase I study (NCT06551142) will enroll ~260 patients, with enrollment currently ongoing. Key eligibility includes: aged ≥18 years, histologically confirmed advanced solid tumors, including those with colorectal cancer, esophageal squamous cell carcinoma, and pancreatic cancer, with measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and no prior B7-H3 treatment. Eligible patients will receive intravenous GSK’227 every 3 weeks (Q3W) until progression, toxicity, loss to follow-up, or death. For Phase 1a, a Bayesian optimal interval design will be used to determine the maximum tolerated dose. Phase 1a primary endpoints are safety and tolerability, including incidences of adverse events (AEs) and serious AEs. Secondary endpoints include objective response rate (ORR), disease control rate, duration of response, immunogenicity, and PK. The Phase 1b primary endpoint is progression-free survival (extensive-stage small cell lung cancer cohort) or ORR (GI and other solid tumors cohort). Secondary endpoints include additional efficacy assessments, PK, safety and tolerability. For Phase 1a and 1b, efficacy will be assessed per RECIST v1.1, with imaging conducted Q6W from first dose then Q12W after 24 weeks. Safety follow-up will be conducted at 30, 60, and 90 (±7) days after the last dose. Safety, tolerability, and efficacy analyses will be conducted using descriptive statistics and, for efficacy analyses, point estimates with 2-sided 95% confidence intervals. This abstract was previously submitted to the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2024 and is submitted on behalf of the original authors with their permission. Funding: GSK (Study 223054). Medical writing support was provided by Avalere Health, funded by GSK.
Clinical trial information: NCT05830123 .
📄 中文摘要 Chinese Abstract
📋 英文结构化总结 English Structured Summary
摘要整理
Background:
B7-H3 is an immune checkpoint protein overexpressed in multiple solid tumors with limited expression in normal tissues. GSK’227 (HS-20093), a novel B7-H3-targeted ADC, is composed of a human anti–B7-H3 monoclonal antibody linked to a topoisomerase I inhibitor via a protease-cleavable linker, and has shown acceptable safety and promising antitumor activity in patients of Asian origin with advanced solid tumors (NCT05276609; NCT05830123). The current study will evaluate the safety, tolerability, efficacy, and pharmacokinetics (PK) of GSK’227 in patients with solid tumors, including GI cancers, in a global population.
Methods:
This two-part (dose-escalation [1a] and expansion [1b]) global, open-label, Phase I study (NCT06551142) will enroll ~260 patients, with enrollment currently ongoing. Key eligibility includes: aged ≥18 years, histologically confirmed advanced solid tumors, including those with colorectal cancer, esophageal squamous cell carcinoma, and pancreatic cancer, with measurable disease per Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1), Eastern Cooperative Oncology Group (ECOG) performance status of 0–1, and no prior B7-H3 treatment. Eligible patients will receive intravenous GSK’227 every 3 weeks (Q3W) until progression, toxicity, loss to follow-up, or death. For Phase 1a, a Bayesian optimal interval design will be used to determine the maximum tolerated dose. Phase 1a primary endpoints are safety and tolerability, including incidences of adverse events (AEs) and serious AEs. Secondary endpoints include objective response rate (ORR), disease control rate, duration of response, immunogenicity, and PK. The Phase 1b primary endpoint is progression-free survival (extensive-stage small cell lung cancer cohort) or ORR (GI and other solid tumors cohort). Secondary endpoints include additional efficacy assessments, PK, safety and tolerability. For Phase 1a and 1b, efficacy will be assessed per RECIST v1.1, with imaging conducted Q6W from first dose then Q12W after 24 weeks. Safety follow-up will be conducted at 30, 60, and 90 (±7) days after the last dose. Safety, tolerability, and efficacy analyses will be conducted using descriptive statistics and, for efficacy analyses, point estimates with 2-sided 95% confidence intervals. This abstract was previously submitted to the European Society for Medical Oncology (ESMO) Immuno-Oncology Congress 2024 and is submitted on behalf of the original authors with their permission. Funding: GSK (Study 223054). Medical writing support was provided by Avalere Health, funded by GSK.
Results:
No results are reported in the provided text; the abstract describes a planned study with ongoing enrollment.
Data Summary:
No quantitative results or key statistics are provided in the text.
Conclusions:
No conclusions are stated in the provided text.
Practical Significance:
No real-world applications or practical significance are discussed in the provided text.
📋 中文结构化总结 Chinese Structured Summary
背景:
B7-H3是一种在多种实体瘤中过表达而在正常组织中表达受限的免疫检查点蛋白。GSK'227（HS-20093）是一种新型B7-H3靶向ADC，由人源抗B7-H3单克隆抗体通过蛋白酶可裂解连接子与拓扑异构酶I抑制剂偶联而成，在亚洲晚期实体瘤患者中已显示出可接受的安全性和良好的抗肿瘤活性（NCT05276609；NCT05830123）。本研究将在全球人群中评估GSK'227在实体瘤（包括胃肠道癌症）患者中的安全性、耐受性、疗效和药代动力学（PK）。
方法:
这项两部分（剂量递增[1a]和扩展[1b]）全球开放性I期研究（NCT06551142）计划入组约260例患者，目前正在入组中。关键入组标准包括：年龄≥18岁，经组织学证实的晚期实体瘤，包括结直肠癌、食管鳞状细胞癌和胰腺癌，根据实体瘤疗效评价标准1.1版（RECIST v1.1）具有可测量病灶，美国东部肿瘤协作组（ECOG）体能状态评分为0-1分，既往未接受过B7-H3治疗。符合条件的患者将每3周（Q3W）静脉输注GSK'227，直至疾病进展、出现毒性、失访或死亡。1a期将采用贝叶斯最优区间设计确定最大耐受剂量。1a期主要终点为安全性和耐受性，包括不良事件（AE）和严重不良事件的发生率。次要终点包括客观缓解率（ORR）、疾病控制率、缓解持续时间、免疫原性和PK。1b期主要终点为无进展生存期（广泛期小细胞肺癌队列）或ORR（GI和其他实体瘤队列）。次要终点包括其他疗效评估、PK、安全性和耐受性。对于1a期和1b期，疗效将根据RECIST v1.1进行评估，影像学检查从首次给药后每6周（Q6W）进行一次，24周后改为每12周（Q12W）进行一次。安全性随访将在末次给药后30天、60天和90天（±7天）进行。安全性、耐受性和疗效分析将采用描述性统计方法，疗效分析将提供点估计值及双侧95%置信区间。本摘要此前已提交至欧洲肿瘤内科学会（ESMO）2024年免疫肿瘤学大会，并经原作者许可代表其提交。资助方：GSK（研究编号223054）。医学写作支持由Avalere Health提供，由GSK资助。
结果:
提供的文本中未报告结果；该摘要描述了一项正在进行入组的计划性研究。
数据摘要:
文本中未提供定量结果或关键统计数据。
结论:
提供的文本中未陈述结论。
实际意义:
提供的文本中未讨论实际应用或实际意义。