977P - Interim results of phase I dose escalation study of YBL-006: A novel anti-PD-1 monoclonal antibody in advanced solid tumors

Background

YBL-006 is a fully human anti-programmed death-1 (PD-1) antibody with a wider binding interface of the PD-1/YBL-006 complex and higher affinity compared to that of other PD-1 antibodies, which showed a favorable safety profile and a potent anti-tumor efficacy in animal models.

Methods

A modified “3+3” design, with the first patient dosed at 0.5 mg/kg (mpk), was followed by conventional dose escalation of 2, 5, and 10 mpk IV. Dose escalation cohort explored the safety, pharmacokinetics (PK), PD-1 receptor occupancy (RO), serum IFN-γ level and tumor response. Adverse events (AEs) were graded using the CTCAE v5. Tumor response was assessed using the RECIST v1.1 every 8 weeks. Exploratory biomarker analysis included whole exome sequencing to assess tumor mutational burden (TMB) and Lunit SCOPE IO to assess the density of intra-tumoral tumor-infiltrating lymphocyte (TIL). The cut-off date for analysis was Apr 27th, 2021.

Results

Total of 11 patients with advanced solid tumors were enrolled in the escalation cohort. YBL-006 showed a linear PK prolife in terms of C_max and area under the curve by dose escalation and approximately 8 days of T_1/2. Both PD-1 RO and serum IFN-γ increased by > 2 times 8 h after the first dose. No dose limiting toxicity (DLTs) or deaths related to YBL-006 have been reported. The most common AEs of Grade 2 ≥ related to YBL-006 were rash (21.7%), fatigue (13%), fever (13%) and hypothyroidism (4.3%). Ten patients were available for tumor response evaluation and their best overall responses included 1 complete response (penile squamous cell carcinoma, 2 mpk), 1 partial response (anal squamous cell carcinoma, 2 mpk) with durable responses lasting more than 30+ and 14+ weeks respectively, and 4 stable disease. Tumor samples of both of 2 responders harbored high levels of TMB (8.3 and 9.3 per megabase) and intra-tumoral TIL density (66.1% and 95.8%).

Conclusions

YBL-006 is well tolerated, and AEs are manageable with the results of no DLTs occurred and the maximum tolerated dose was not reached until progressing to the 10 mpk. Dose expansion cohort using flat dosing is planned.

Clinical trial identification

NCT04450901.

Editorial acknowledgement

Legal entity responsible for the study

Y-Biologics Inc.

Funding

Y-Biologics Inc.

Disclosure

M. Kim: Financial Interests, Personal, Full or part-time Employment: Y-Biologics; Financial Interests, Personal, Stocks/Shares: Y-Biologics. J. Yoon: Financial Interests, Personal, Full or part-time Employment: Y-Biologics; Financial Interests, Personal, Stocks/Shares: Y-Biologics; Non-Financial Interests, Project Lead: Y-Biologics. H. Lee: Financial Interests, Personal, Full or part-time Employment: Y-Biologics; Financial Interests, Personal, Stocks/Shares: Y-Biologics; Financial Interests, Personal, Leadership Role: Y-Biologics. All other authors have declared no conflicts of interest.