A phase I/II study of KD6001, a novel fully human anti-CTLA4 IgG1 monoclonal antibody, in combination with toripalimab in patients with advanced melanoma.

9527 Background: Anti-CTLA4 and anti-PD-1 immunotherapies have changed the treatment landscape of patients (pts) with advanced or metastatic melanoma. However, there is still a need to develop an anti-CTLA-4 antibody with further improved safety and efficacy profile. KD6001, a novel fully human anti-CTLA4 IgG1 monoclonal antibody that exhibits immunomodulatory effects, enhances T-cell-mediated anti-tumor immune response, and shows preliminary anti-tumor activity as monotherapy in a FIH phase I trial in pts with advanced solid tumors. Here we report a new study result of KD6001 in combination with toripalimab, an anti-PD-1 monoclonal antibody, in pts with advanced melanoma (KD6001CT02). Methods: KD6001CT02 is a phase I/II study conducted in advanced melanoma. This study consists of dose escalation and dose expansion phases. The primary objective is to evaluate the safety and tolerability of KD6001 in combination with toripalimab and determine the MTD/RP2D. The secondary objectives are to measure antitumor activity, immunogenicity, and pharmacokinetics (PK). Results: As of 15 Dec 2023, 29 pts with melanoma were enrolled (dose escalation n=6 and dose expansion n=23), including 9 (31.0%) acral, 9 (31.0%) nonacral cutaneous, 8 (27.6%) mucosal, and 3 (10.3%) unknown primary subtypes. 18 of them had no brain metastases. The median age was 56 yrs (range 41-78 yrs). The majority of pts previously received anti-PD-1/L1 therapy (16/29, 55.2%) and 27.6% of them received ≥3 lines of therapy. No dose-limiting toxicity or ≥Gr 3 adverse events (AEs) were reported in the dose escalation phase. The study did not reach MTD. 26 (89.7%) pts had treatment-related adverse events (TRAEs), with ≥Gr 3 TRAEs occurring in 3 (10.3%) pts and were well manageable. All other TRAEs were Gr 1 or 2. There were no death events due to TRAEs. No novel safety signals were seen other than the previously reported safety profile of treatment with a combined inhibition of CTLA-4 and PD-1. At data cutoff, among 13 efficacy-evaluable pts without brain metastases, the unconfirmed and confirmed objective response rates (ORR) were 38.5% and 23.1%, respectively. The disease control rate (DCR) was 76.9%. Among 3 pts with confirmed partial response (PR) , 2 pts were mucosal melanoma and 1 patient was nonacral cutaneous melanoma. Among 7 pts who received KD6001 as the ≥2 line treatment and all failed anti-PD-1/L1 therapy, the unconfirmed and confirmed ORR were 57.1% and 42.9%, respectively. DCR was 85.7%. The median PFS and OS were not reached. Conclusions: KD6001 in combination with toripalimab for treatment of advanced melanoma was safe, well-tolerated and showed anti-tumor activity in pts with advanced melanoma. Preliminary analysis indicates that KD6001 combined with toripalimab is efficacious in pts who have progressed after previous anti-PD-1/L1 therapy and in pts with mucosal melanoma. Clinical trial information: NCT05723432 .