Pembrolizumab Combined with Disitamab Vedotin in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Colorectal Cancer
Xiaojing Xu, Minzhi Lv, Luoyan Ai, Qing Wang, Yuehong Cui, Wei Li, Qing Liu, Xi Tang, Xi Chen, Shan Yu, Mengzhou Guo, Yiyi Yu, Tianshu LiuAbstract
Background
Late-line treatment options for microsatellite stable (MSS)/proficient mismatch repair (pMMR) metastatic colorectal cancer (mCRC) are limited. PD-1 blockade alone has minimal clinical benefit in this population. Human epidermal growth factor receptor 2 (HER2)-targeted therapies represent an emerging strategy for HER2-expressing mCRC. This study evaluated the efficacy and safety of pembrolizumab combined with disitamab vedotin (DV), an anti-HER2 antibody-drug conjugate (ADC), in pretreated patients with HER2-positive mCRC.
Methods
This multicenter, single-arm, phase II study enrolled patients with MSS/pMMR, HER2-positive mCRC who received 2 prior lines of systemic therapy. Patients received pembrolizumab 400 mg every 6 weeks plus DV 2.5 mg/kg every 2 weeks until disease progression, unacceptable toxicity, or death. Primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety.
Results
Between December 2022 and May 2024, 15 patients (median age 59.0 years; 60.0% male) were enrolled. Fourteen patients (93.3%) had HER2 IHC 3+ expressions, and two had received prior anti-HER2 therapy. Two patients achieved partial response, (ORR=13.3%; 95% CI, 1.7%-40.5%). With median follow-up of 26.7 months, median PFS was 2.9 months (95% CI, 2.3 to not reached). Median OS was not reached (95% CI, 16.7 to NR). The 6-month OS rate of 92.9% (95% CI: 6.9%-80.3%) and the 1-year OS rate was 71.4% (95% CI: 51.3%-99.5%). The most common treatment-related adverse events (TRAEs) included nausea, anorexia, alanine aminotransferase elevation, aspartate aminotransferase elevation, and alopecia. Grade 3-4 TRAEs occurred in two patients (14.3%), both neutropenia.
Conclusions
Pembrolizumab plus disitamab vedotin showed limited antitumor activity in pretreated HER2-positive mCRC.
ClinicalTrials.gov Identifier
NCT05333809