I-Mab announced preliminary Phase 2 clinical trial data for uliledlimab, a differentiated CD73 antibody, in combination with toripalimab for patients with non-small cell lung cancer (NSCLC). The data, with a cutoff date of March 29, 2022, showed encouraging efficacy signals, particularly in patients with advanced NSCLC who were previously ineligible for standard of care. The company aims to initiate a Phase 3 study in NSCLC in 2023.
Uliledlimab's Safety and Efficacy Profile
The Phase 2 trial (NCT04322006) assessed uliledlimab's safety and efficacy. Uliledlimab was well-tolerated up to 30 mg/kg Q3W, with no dose-limiting toxicities observed as a monotherapy or in combination with toripalimab. The study also confirmed uliledlimab's linear pharmacokinetic profile at doses ≥5mg/kg and dose-dependent receptor occupancy, avoiding the "hook effect" seen in other CD73 antibodies.
Clinical Response in NSCLC Patients
Clinical responses varied among the three NSCLC patient cohorts studied. The cohort with advanced NSCLC (mostly stage 4) who were previously ineligible for standard of care showed the highest response rates. Among 19 efficacy-evaluable patients in this cohort, 5 partial responses (PR) were observed, resulting in an overall response rate (ORR) of 26%, and 9 patients had stable disease (SD), leading to a disease control rate (DCR) of 73.7%.
Notably, approximately 80% of patients in this cohort had low PD-L1 expression (TPS 1-49% or TPS<1%) and are typically considered less responsive to checkpoint inhibitor therapy. Historical data from KEYNOTE-042 showed an ORR of 16.9% in patients with PD-L1 TPS of 1-49%.
CD73 Expression as a Potential Biomarker
The clinical response observed in the NSCLC cohort displayed a correlation with CD73 expression in tumors. High CD73 expression (≥35% expression level in tumor cells or immune cells) was found in 4 out of 5 PRs, with a mean value of 53.4%, and in 4 out of 9 SDs, with a mean value of 30.5%. None of the 5 patients who progressed on the treatment showed high CD73 expression, with a mean value of 19.2%.
Future Clinical Development
I-Mab plans to expand the Phase 2 study to further evaluate treatment efficacy and the role of CD73 as a potential predictive biomarker in a selected NSCLC patient cohort. The company anticipates initiating a Phase 3 registrational clinical trial in NSCLC patients, pending approval from the China National Medical Products Administration, and another clinical trial in the United States in other selected cancer types, potentially beyond combination with PD-1/PD-L1 therapy, within the next 12 months.
Professor Yi-Long Wu, Principal Investigator of the study, commented, "The data represent a step forward for advanced non-small-cell lung cancer patients. To date, uliledlimab has shown a favorable safety profile and positive anti-tumor activity in lung cancer patients, particularly in those patients with a higher baseline CD73 expression."
