Authors: Vinod Ganju, Adam Cooper, Bo Gao, Kate Wilkinson
Published: 2022-06-06
DOI: 10.1200/jco.2022.40.16_suppl.2602
Source: Full article
2602 Background: YH001 is a humanized anti-hCTLA-4 IgG1 mAb that relieves CTLA-4-mediated immunosuppression, and thereby enhances the T-cell-mediated antitumor immune response. Pre-clinical data have shown potent anti-cancer activity when combined with anti-PD-1 mAb. Methods: This is an ongoing phase 1 dose-escalation study conducted in Australia. Patients (pts) with advanced solid tumors received YH001 by IV administration at 0.05 to 6.0 mg/kg for 1 cycle (21 days) then in combination with Toripalimab (anti-PD-1 mAb) at 240 mg Q3W for 4 cycles. An accelerated titration method followed by the standard "3+3" design was utilized to evaluate safety, tolerability and preliminary efficacy. Results: As of 31-Dec-2021 data cut-off, 24 pts with advanced solid tumors were enrolled and dosed at 0.05 mg/kg (n=2), 0.1 mg/kg (n=3), 0.3 mg/kg (n=3),1mg/kg (n=5), 2mg/kg (n=5), 4mg/kg (n=3) and 6mg/kg (n=3). Baseline ECOG scores were 0 (n=14), 1 (n=10) with all pts progressed after a median of 2 prior lines of available standard therapy (range 1-5) including 5 pts progressed after prior immunotherapy of anti-PD-1 antibody. Overall, 6 cases of Grade(G) 3 or above treatment-related AEs (TRAEs) have been reported in 5 pts at 0.3 mg/kg, 4 mg/kg and 6 mg/kg dose level respectively, including 1 G3 colitis, 1 G4 thrombocytopenia, 1 G3 Enterocolitis, 1 G3 Rash, 1 G3 Pruritus and 1 G3 hepatitis. There were no death events due to TRAEs. 18 pts (75%) had 63 TRAEs of any level, including 28 G1 TRAEs, 29 G2 TRAEs. 2 of the first 3 pts at MAD (6mg/kg) met protocol defined DLT in Combo phase. Among the 23 pts having imaging tumor assessment by RECIST v1.1, 4 achieved PR and 9 achieved SD in Best of Response. 1 subject with gastroesophageal junction carcinoma at 0.3 mg/kg has achieved PR since the 2nd tumor assessment, target lesion decreased by up to 84.5% from baseline. 1 subject with urothelial carcinoma at 2 mg/kg progressed after prior anti-PD-1 antibody has achieved PR since the 2nd tumor assessment, target lesion decreased by up to 74% from baseline. 1 subject with uterine carcinosarcoma at 2 mg/kg has achieved PR since the 1st tumor assessment, target lesion decreased by up to 52.3% from baseline. 1 subject with vulva adenocarcinoma at 6 mg/kg has achieved PR since the 1st tumor assessment, target lesion decreased by up to 71.4% from baseline. ORR (CR+PR) and DCR (CR+PR +SD) were 17.4%, 56.5% respectively. Conclusions: YH001 was well tolerated up to 4 mg/kg dose levels when combined with toripalimab and has shown encouraging antitumor activity in patients with advanced solid tumors. Clinical trial information: NCT04357756.