Phase I Study of Telisotuzumab Adizutecan (Temab-A, ABBV-400), a Novel c-Met Antibody-Drug Conjugate, in Patients With Late-Line Colorectal Cancer and Advanced Solid Tumors.

A first-in-human phase I study (ClinicalTrials.gov identifier: NCT05029882) of Temab-A in patients with advanced solid tumors whose disease has progressed is currently ongoing.

一项首次人体的I期临床研究（ClinicalTrials.gov注册号：NCT05029882）目前正在对疾病进展的晚期实体瘤患者进行Temab-A的研究。

We report results from all patients in the dose escalation and the monotherapy metastatic colorectal cancer (mCRC) dose expansion.

我们报告了剂量递增和单药治疗转移性结直肠癌（mCRC）剂量扩展中所有患者的结果。

Methods

Temab-A was administered intravenously once every 3 weeks as a monotherapy starting at 1.6 mg/kg in dose escalation.

Temab-A以1.6 mg/kg的剂量开始，每3周通过静脉注射一次作为单药治疗。

In mCRC dose expansion, patients with confirmed BRAF wild-type, microsatellite stable/mismatch repair-proficient mCRC were randomly assigned to 1.6 mg/kg, 2.4 mg/kg, or 3.0 mg/kg Temab-A once every 3 weeks.

在转移性结直肠癌（mCRC）剂量扩展研究中，经确认为BRAF野生型、微卫星稳定/错配修复功能正常的mCRC患者被随机分配至每3周一次接受1.6 mg/kg、2.4 mg/kg或3.0 mg/kg Temab-A治疗。

Primary end points included safety, pharmacokinetics, recommended phase II dose of Temab-A monotherapy, and Temab-A efficacy in patients with mCRC.

主要终点包括安全性、药代动力学、Temab-A单药治疗推荐的II期剂量，以及Temab-A在mCRC患者中的疗效。

Results

In total, 57 patients received ≥1 dose of Temab-A in dose escalation; 3.0 mg/kg once every 3 weeks was established as the maximum tolerated dose.

共有57名患者在剂量递增阶段接受了≥1剂Temab-A治疗；确定每3周一次3.0 mg/kg为最大耐受剂量。

Collectively, in dose escalation and dose expansion, 122 patients with mCRC received Temab-A (dose escalation, N = 29; randomized dose optimization expansion, N = 93).

在剂量递增和剂量扩展阶段，共有122名转移性结直肠癌（mCRC）患者接受了Temab-A治疗（剂量递增阶段，N=29；随机剂量优化扩展阶段，N=93）。

All patients experienced ≥1 treatment-emergent adverse event; the most frequent were gastrointestinal (78%) and hematologic (71%) toxicities.

所有患者均经历了≥1种治疗相关的不良事件；最常见的不良事件是胃肠道（78%）和血液学（71%）毒性。

Treatment-related discontinuations and deaths were infrequent (10% and 3%, respectively).

与治疗相关的停药和死亡情况较少见（分别为10%和3%）。

Across all doses in patients with mCRC, overall response rate was 15.6% (95% CI, 9.6 to 23.2), disease control rate was 74.6% (95% CI, 65.9 to 82.0), and duration of response was 5.9 months (95% CI, 4.1 to 10.5); responses were more frequent at doses of 2.4 mg/kg and 3.0 mg/kg once every 3 weeks.

在所有剂量组的转移性结直肠癌(mCRC)患者中，总缓解率为15.6%（95%置信区间，9.6至23.2），疾病控制率为74.6%（95%置信区间，65.9至82.0），缓解持续时间为5.9个月（95%置信区间，4.1至10.5）；在每3周一次2.4 mg/kg和3.0 mg/kg剂量组中，缓解更为频繁。

Median progression-free survivalwas 4.6 months (95% CI: 4.0, 5.4), and median overall survivalwas 10.4 months (95% CI, 8.9 to 13.1).

中位无进展生存期为4.6个月（95%置信区间：4.0, 5.4），中位总生存期为10.4个月（95%置信区间，8.9至13.1）。

Conclusions

Temab-A at 2.4 mg/kg once every 3 weeks has a tolerable and manageable safety profile, with promising antitumor activity.

每3周一次，每次2.4 mg/kg的Temab-A具有可耐受和可管理的安全性特征，并显示出有希望的抗肿瘤活性。