编者按：2024年9月13日~17日，备受瞩目的欧洲肿瘤内科学会（ESMO）年度盛会于西班牙巴塞罗那如期召开。在此盛会上，我国肿瘤领域的杰出学者、北京大学肿瘤医院沈琳教授三项最新科研成果成功入选大会壁报展示环节，彰显了我国学者在肿瘤研究领域的卓越贡献。沈琳教授一贯强调要以临床问题为导向设计临床研究，最终解决临床难题，此番三项研究正是这一科学精神的生动实践。《肿瘤瞭望消化时讯》特此精心梳理了这三项壁报的核心内容，旨在为读者呈现一场学术盛宴，共襄肿瘤学最新进展。

经多重预处理的晚期HER2阳性实体瘤患者该何去何从？

背景

方法

结果

结论

如何进一步改善HER2阴性转移性胃/胃食管结合部腺癌患者的一线治疗效果？

背景

方法

结果

结论

免疫失败后，患者该如何寻找新的治疗出路与希望？

背景

方法

结果

结论

摘要原文

675P - Evaluation of the safety and efficacy of JSKN003 in patients with advanced HER2-positive (IHC 3+) solid tumors (excluding breast cancer)

Saturday, 14 September 2024

Background

JSKN003 is a novel HER2-directed antibody-drug conjugate (ADC) conjugated to a topoisomerase I inhibitor via a dibenzocyclooctyne tetrapeptide linker on the glycans of a humanized bispecific antibody. JSKN003-101 and JSKN003-102 is dose escalation and expansion studies in Australian and Chinese patients (pts) with metastatic solid tumors.

Methods

This is pooled analysis from pts enrolled in JSKN003-101 and JSKN003-102 with histologically documented HER2-positive (IHC 3+) solid tumors who failed prior systemic therapies, received JSKN003 monotherapy intravenously Q3W. The objectives were safety and efficacy of JSKN-003.

Results

As of 15th Mar 2024, 24 pts (7 CRC, 5 GC, 3 ESCA, 2 OC, 2 BTC, and 5 others) were enrolled and JSKN003 dosed across 6 dose levels, including 2.1 mg/kg, 4.2 mg/kg, 5.2 mg/kg, 6.3 mg/kg, 7.3 mg/kg and 8.4 mg/kg. 10 pts (41.7%) received ≥ 3 prior lines of therapy,6 pts(25%) received anti-HER2 ADC. The median duration of treatment was 13.9 (range,9.4,19.8) weeks, and 20 pts (83.3%) remained on treatment. Treatment-related adverse events (TRAEs) occurred in 23 pts (95.8%), and the mostly common grade 1 and 2 TRAEs were diarrhea (62.5%) and nausea (58.3%), infusion related reaction (29.2%), fatigue (25.0%).5 pts (20.8%) experienced grade ≥3 TRAEs, were neutropenia (8.3%), vomiting (4.2%), fatigue (4.2%) and abdominal discomfort (4.2%). 2 pts had interstitial lung disease, grade 2 (occurred in 6.3 mg/kg), both recovered thereafter. No TRAE led to death or discontinuation. 22 pts with tumor assessment, the ORR and DCR were 72.7% (95%CI: 49.8, 89.3) and 95.5% (95%CI: 77.2, 99.9). 5 pts who received prior anti-HER2 ADC, the ORR was 80% and median DOR was more than 30 weeks.

Conclusions

JSKN003 was well tolerated with encouraging preliminary antitumor activity in heavily pretreated pts with advanced HER2-positive (IHC ≥ 3+) solid tumors, which support further clinical development.

Clinical trial identification

NCT05494918; NCT05744427.

1410P - Efficacy of fruquintinib plus paclitaxel (F+PTX) in patients (pts) with prior immunotherapy (prior-IO): Subgroup analysis from FRUTIGA study

Speakers：Lin

Shen (Beijing, China)

Background

FRUTIGA has previously reported that F+PTX significantly improved PFS, ORR and DCR in 2L treatment of pts with advanced gastric or gastroesophageal junction (G/GEJ) adenocarcinoma. Treatment landscape of gastric cancer has evolved in the past few years. Immunotherapy plus chemotherapy with or without HER2-targeted therapy is the new standard of care for 1L therapy especially in pts with high PD-L1 expression, while the immunotherapy was not accessible in China at the initiation of FRUTIGA in 2017.

Methods

Pre-defined and post hoc analyses were conducted to evaluate the efficacy of F+PTX compared with placebo plus paclitaxel (PBO+PTX) in pts who received prior-IO in FRUTIGA.

Results

Of the 703 pts enrolled in FRUTIGA, 82 had received prior-IO. Of these, 35 were treated with F+PTX and 47 with PBO+PTX. Baseline demographics and disease characteristics were comparable between treatment arms. The most commonly used prior-IO were sintilimab (20.7%) and tislelizumab (19.5%). PFS was longer with F+PTX versus PBO+PTX (mPFS, 6.4 vs 1.8 months, HR 0.38; p=0.0003). Higher ORR and DCR were also observed in F+PTX (57.1% vs 19.1% and 82.9% vs 42.6%, respectively) compared with PBO+PTX. However, OS was not statistically significant (mOS, 12.1 vs 10.3 months, HR 0.99). It showed the same benefit trends of PFS, ORR and DCR in pts with prior-IO, in consistent with ITT population. Pre-defined subgroup analysis showed that pts with prior-IO might further reduce the risk of death or progression (HR 0.38) compared with those received prior chemotherapy only (HR 0.62) or the ITT population (HR 0.57). Detailed information is provided in the table. Table: 1410P

Conclusions

F+PTX also demonstrated efficacy benefits and showed great clinical value in prior-IO exposed pts.

Clinical trial identification

NCT03223376.

1419P - Osemitamab (TST001) plus nivolumab and CAPOX as the first-line therapy for the patients with advanced G/GEJ cancer (TranStar102)

Speakers：Lin

Shen (Beijing, China)

Background

Osemitamab, a humanized monoclonal antibody with improved affinity to Claudin 18.2 (CLDN18.2) and enhanced antibody-dependent cell-mediated cytotoxicity, has exhibited synergistic effect with anti-PD-1 antibody and chemotherapy in pre-clinical studies. As checkpoint inhibitor plus chemotherapy is the current standard of care (SOC), we explored the combination of osemitamab with this SOC for the treatment of the CLDN18.2 positive 1L G/GEJ cancer patients.

Methods

Cohort G from TranStar102, a phase I/IIa study (NCT04495296), is designed to evaluate the safety and efficacy of osemitamab at doses of 3mg/kg or 6mg/kg Q3W plus nivolumab and CAPOX as the 1L treatment for patients with G/GEJ cancer. Advanced G/GEJ cancer patients with HER2 negative or unknown, regardless of CLDN18.2 or PD-L1 expression, were enrolled. CLDN18.2 and PD-L1 status were analyzed retrospectively using IHC 14G11 LDT assay and PD-L1 IHC 28-8 pharmDx at a central laboratory.

Results

As of April 18, 2024, 82 patients were dosed with osemitamab plus nivolumab and CAPOX (40 at 3mg/kg, 42 at 6mg/kg) with median follow-up 12.6 months. All patients experienced treatment-related adverse events (TRAE). The most common TRAE were hypoalbuminaemia, nausea and vomiting, most of them were of CTC AE grade 1 or 2 and manageable. Here we report the efficacy of patients with high/medium CLDN18.2 expression group in overall (n=32) and in subgroup with PD-L1 CPS less than 5 (n=22). The progression-free survival was 12.3 and 12.6 months, the objective response rate was 58.1% and 71.4%, respectively. The median duration of response (DoR) was not reached. Updated clinical data and details by biomarkers levels will be reported at the time of the conference.

Conclusions

Updated data indicate that the combination of TST001 plus nivolumab and CAPOX as the 1L treatment for patients with G/GEJ cancer is safe and well tolerated with very encouraging anti-tumor activities, especially for patients with high/medium CLDN18.2 expression when cross comparing to historical data.

专家简介

沈琳教授