Multicenter phase 1 trial of disitamab vedotin plus toripalimab for advanced G/GEJ and other solid tumors

Disitamab vedotin (RC48) is a novel antibody drug conjugate comprising hertuzumab coupled with monomethyl auristatin E via a cleavable linker. Preclinical studies found synergy of RC48 and PD-1 inhibitors. A phase 1 trial at three centers in China evaluated the combination of RC48 and toripalimab among pretreated patients with advanced G/GEJ cancer and other solid tumors expressing HER2. The safety profile was manageable. The recommended phase 2 dose (RP2D) was RC48 2.5 mg/kg plus toripalimab 3 mg/kg, every two weeks. The figure shows that among the patients with G/GEJ cancer (panel A) the confirmed objective response rate was 43%, while among patients with other tumors (panel B), antitumor activity was seen for breast cancer (5 of 13 patients) and endometrial carcinoma (1/1). Among G/GEJ cancer patients receiving the RP2D, the ORR was 50% (95% CI 28-72) with a median PFS of 5.1 months (1.4-7.3) and a median OS of 14.0 months (6.3-NE). Among patients with G/GEJ cancer receiving the RP2D, a clinical benefit was seen in both HER2-positive and low HER2 expressing populations. The authors conclude that RC48 plus toripalimab had a manageable safety profile and encouraging efficacy among pretreated patients with HER2-positive and low HER2-expressing G/GEJ cancer.