Safety and efficacy of YBL-006, an anti-PD-1 monoclonal antibody in advanced solid tumors: A phase I study.

Abstract

e14557 Background: YBL-006 is a fully human anti-programmed death-1 (PD-1) antibody under evaluating its safety and efficacy in phase I clinical trial. We have reported interim analysis of dose escalation cohort which showed a tolerable safety profile. Here, we present the updated clinical activity of YBL-006 in dose escalation and expansion cohorts. Methods: Dose escalation (0.5, 2, 5, 10 mg/kg) and dose expansion (flat doses of 200 mg every 2 weeks [Q2W] and 300 mg every 3 weeks [Q3W]) cohorts explored the safety, pharmacokinetics (PK) and objective response rate (ORR) in the patients with advanced solid tumors who failed or were ineligible to the standard of care. Adverse events (AEs) were graded using the CTCAE v5. ORR was assessed using the RECIST (v1.1). Lunit SCOPE IO, an H&E analysis tool, was applied as an exploratory biomarker, and samples with “Immune inflamed phenotype” were defined as those with high intratumoral TIL density in ≥ 20% of the tumor microenvironment. The cut-off date for analysis was Jan 4th, 2022. Results: A total of 67 patients (safety set) with advanced solid tumors were enrolled in the study. Median follow-up duration of the safety set was 1.6 months (range 0.2-16.8). There was no dose-limiting toxicity during dose escalation phase. Most frequent AEs were grade 1 or 2; fatigue (19.4%), pruritus (10.4%), and fever (7.5%), and two hypothyroidism (3.0%), one pneumonitis (1.5%), and one cytokine-releasing syndrome (1.5%) were observed. One subject experienced grade 3 diarrhea in the safety set. PK study showed that half-life was 8.0 days, and mean Cmax and AUC0-inf were 4.15 x 104 ng/ml and 1.12 x 107 ng/ml*h for 200 mg dose, and 6.26 x 104 ng/ml and 1.53 x 107 ng/ml*h for 300 mg dose, respectively. A total of 52 patients were evaluable for efficacy. ORR was 15.4%, including 1 complete response (penile squamous cell carcinoma [SqCC]), and 7 partial responses (two gastric adenocarcinomas, anal SqCC, paranasal sinus SqCC, nasopharyngeal carcinoma, neuroendocrine carcinoma, and thyroid Hurthle cell carcinoma). Durable responses were seen in 2 patients for over 12 months. Median duration of response was 4.9 weeks (range 1-65). Among efficacy set, 32 samples were available for Lunit SCOPE IO. ORR was significantly higher in inflamed immune phenotype compared to non-inflamed samples (62.5% vs 8.3% p = 0.005). Conclusions: Interim analysis of phase I trial of YBL-006 shows a tolerable safety profile and clinical activity. Notable anti-tumor efficacy was observed in inflamed immune phenotype. Clinical trial information: NCT04450901.