A first-in-human, phase I, dose-escalation study to evaluate pharmacokinetics, safety, and tolerability of KD6001, a novel anti-CTLA-4 monoclonal antibody (mAb) in patients with advanced solid tumors.
Authors: Tang Bixia , Duan Rong , Li Siming , Sheng Xinan , Si Lu , Cui Chuanliang , Mao Lili , Wang Xuan , Lian Bin , Wei Xiaoting , Yan Xieqiao , Li Juan , Zhou Li , Xu Huayan , Li Caili , Cai Zeling , Zhang Chi , Wang Fangfang , Guo Jun , Chi Zhihong 
Published: June 2024

e14501

Background: KD6001, a novel fully human anti-CTLA4 IgG1 monoclonal antibody, exhibits immunomodulatory effects, enhances T-cell-mediated antitumor immune response and shows promising activity in preclinical models of solid tumors. Here we present the pharmacokinetics, safety and tolerability data from the phase 1 study of KD6001 (NCT05230290) in patients with advanced solid tumors. Methods: patients were enrolled in a 3+3 dose escalation phase 1 study with the following pre-defined KD6001 cohorts: 0.2mg/kg, 1mg/kg, 3mg/kg or 6mg/kg, every 2 weeks via intravenous infusion for 4 cycles. The primary objective was to evaluate the safety and tolerability of KD6001 and determine the MTD/RP2D. The secondary objectives were to measure antitumor activity, immunogenicity and pharmacokinetics (PK). All AEs are graded using NCI CTCAE v5.0. Efficacy assessments are per RECIST 1.1. Blood samples are obtained for pharmacokinetics (PK) and for immunogenicity assessments, measured by the development of anti-drug antibodies. Results: The study had been completed. Thirteen pts with melanoma had been enrolled and treated at 0.2 mg/kg (n = 1), 1mg/kg (n = 3), 3 mg/kg (n = 6) and 6mg/kg (n = 3) at Beijing Cancer Hospital. The average age was 57.2 years (range 34-68). Baseline ECOG scores were 0 (n = 5), 1(n = 8) with all pts. Seven pts (53.85%) received ≥ 2 lines of previous systemic therapies and 12 pts (92.31%) received previous PD-1/PD-L1 treatment. KD6001 was well-tolerated with no dose-limiting toxicities (DLTs) observed, nor was the MTD reached at the highest doses administered. All the thirteen pts had at least one adverse event during treatment, and eleven of them (84.62%) had Treatment Related Adverse Events (TRAEs), most of which were Grades 1-2. There were no permanent drug discontinuation or deaths due to adverse events. Pharmacokinetic analysis indicated a linear correlate between the drug exposure (Cmax, AUC0-t and AUC0-inf) and study drug dosages evaluated. The geometric mean T1/2 was 10 days (CV%: 31%). The peak concentration and exposure level increased proportionally to dose from 0.2mg/kg to 6 mg/kg. No anti-drug antibodies were detected in any of the patient’s serum samples. Clinical efficacy was observed in 12 evaluable pts: 3 patients at 3mg/kg had a stable disease (SD) and 1 patient at 3mg/kg had a confirmed partial response (PR). The ORR of the 3mg/kg dose group was 16.7% (1/6), the DCR was 66.67% (4/6). The median PFS was 109 days and the median OS was not reached. Conclusions: KD6001 showed promising antitumor activity and a tolerable safety profile in patients with advanced solid tumors. Hence, 3mg/kg was selected as the RP2D. Clinical trial information: NCT05230290 .