HBM4003 is a fully human heavy chain only monoclonal antibody targeting CTLA-4. In addition to blocking the CTLA-4 pathway, HBM4003 is also engineered to deplete Treg cells by enhanced antibody-dependent cellular cytotoxicity (ADCC) activity that was clinically validated. Here we reported updated results of a phase I study that evaluated HBM4003 plus toripalimab (anti-PD-1 antibody) in advanced melanoma.
This study includes two parts. In the dose-escalation part, patients with solid tumors received HBM4003 at 3 dose levels (0.03 mg/kg [n=1], 0.1 mg/kg [n=3], and 0.3 mg/kg [n=10]) plus toripalimab 240 mg every three weeks (Q3W). In the dose-expansion part, patients with advanced melanoma (n=26) received the recommended phase 2 dose (RP2D) of HBM4003 0.3 mg/kg plus toripalimab 240 mg Q3W.
As of 27 Jun 2022, a total of 40 patients had been dosed. Median follow-up time was 106.5 days. Treatment-related adverse events (TRAEs) were reported in 85.0% (34/40) patients, and ≥Grade 3 TRAEs were reported in 20.0% (8/40) patients. The most commonly reported TRAE was rash (30.0%). Patients with advanced melanoma treated with RP2D (including 8 patients in Part 1 and 26 patients in Part 2) were categorized as anti-PD-(L)1 naïve group (Cohort A, 17 patients) and anti-PD-(L)1 pretreated group (Cohort B, 17 patients). For cohort A, the ORR and DCR were 53.3% (95%CI: 26.6-78.7) and 73.3% (95%CI: 44.9-92.2) respectively in the 15 patients with post-treatment tumor assessment. The ORR of cutaneous, acral, mucosal and unknown subtype were 66.7% (2/3), 50% (2/4), 60.0% (3/5) and 33.3% (1/3), respectively. For Cohort B, the ORR and DCR were 11.8% (95%CI: 1.5-36.4) and 35.3% (95%CI: 14.2-61.7) respectively, including one patient achieving PR after pseudo-progression. Both of the PR cases were mucosal subtype.
HBM4003 0.3 mg/kg plus toripalimab 240mg Q3W showed promising anti-tumor activity in anti-PD-(L)1 naive patients with advanced melanoma including acral and mucosal subtypes, as well as an acceptable safety profile.
Clinical trial identification
Legal entity responsible for the study
Peking University Cancer Hospital.
All authors have declared no conflicts of interest.