(T-058) Exposure-response (E-R) relationship between PD-L1 recombinant monoclonal antibody IMC-001 in relapsed or refractory extranodal NK/T cell lymphoma nasal type patients

Taewook Sung, NA – MS course student, Chungnam National University; Won Seog Kim, Ph.D., MD – Professor, Principal Investigator of clinical trial, Samsung Medical Center, Sungkyunkwan University School of Medicine; Sung Young Lee, MS – Head of Clinical Strategy and Operation, ImmuneOncia Therapeutics, Inc; SuYeon Kim, BS – Manager of clinical trial, ImmuneOncia Therapeutics, Inc; Seongyeon Kang, BS – Lead of clinical trial, ImmuneOncia Therapeutics, Inc; Sung Ho Kim, Ph.D. – Chief Technology Officer, ImmuneOncia Therapeutics, Inc; Heung Tae Kim, Ph.D., MD – Chief Medical Officer, ImmuneOncia Therapeutics, Inc; Soyoung Lee, Pharm.D., Ph.D. – Assistant Professor, Chungnam National University; Jung-woo CHAE, Ph.D – Associate Professor, Chungnam National University; Hwi-yeol Yun, Ph.D – Professor, Chungnam National University

Objectives: IMC-001 is a fully human IgG1 monoclonal antibody that binds to human PD-L1 (programmed death-ligand 1). The aim of this study was to conduct IMC-001 exposure-response (E-R) relationships of patients with relapsed or refractory extranodal NK/T cell lymphoma nasal type (ENKTL) enrolled in ongoing phase 2 clinical trials who received IMC-001 20mg/kg every 2 weeks (Q2W).

Methods: Population pharmacokinetic (pop PK) model for exposure representation was used previous reported model, developed by phase I for IMC-001 2, 5, 10, 15, 20 mg/kg Q2W (n=15) and phase II for 20 mg/kg Q2W dosage, respectively. For evaluation of E-R relationship, pop PK model was applied as an exposure prediction for each ENKTL patient who are experienced at least one IMC-001 dosing in phase 2 trial, and those were compared with minimum effective exposure (MEC). In addition, objective response (OR) based on best overall response (BOR) of complete response (CR) or partial response (PR), what it assessed per the Lugano criteria with LYRIC modification for lymphoma, was explored as a response. The logistic regression model was employed to quantitate E-R relationship. The final E-R model was selected based on overall model performance, including the examination of parameter precision, objective function value (OFV), goodness of fit (GOF) plots and model prediction performance.

Results: Exposure, as calculated by a pop PK model, was assessed through average (Cavg), maximum (Cmax), and trough concentrations (Ctrough) over a two-week period following each patient's last dose. It was confirmed that all exposures consistently remained above the minimum effective concentration (MEC) level (>3 mcg/mL). To establish an E-R relationship, these exposure metrics were treated as independent variables to assess the likelihood of achieving an OR within each model. All exposures exhibited significant regression coefficients (β1) with 95% Cis but following numerical and visual diagnosis, Ctrough selected as the most suitable predictor in the regression model. This model demonstrated 6.308 reduction of OFV compared to the null hypothesis logistic regression model, also indicated a reasonable GOF. The model estimated an intercept (β0) was 0.59 and β1 was 0.0282 (95% CI was [0.002, 0.054]). When odds ratios referenced by the median Ctrough were assessed, there was a trend toward an increase in probability of OR with increasing exposure with odds ratios of 0.16 [0.041-0.62] for the 5th percentile and 3.3 [1.4-8.5] for the 95th percentile.

Conclusions: This E-R analysis effectively evaluated the relationship between exposure and efficacy response. With the probability of achieving an OR showing a tendency to increase with rising exposure levels and considering that exposure has already surpassed the MEC threshold, we anticipate that IMC-001 will demonstrate favorable effects for future development.

Citations: [1] Sung et al. PAGE (2024) Poster presentations
[2] Keam, humus et al. (2021)