Phase I Clinical Trial Results of Qilu Pharmaceutical's Iparomlimab (QL1604) Published in Frontiers in Immunology

JinanNovember 2, 2023PR Newswire -- Recently, the Phase I study results of Qilu Pharmaceutical's Aipalolimab (research code: QL1604) were published online in the academic journal *Frontiers in Immunology* (2022 Impact Factor: 7.3). The title of the paper is *"A First-in-Human, Open-Label, Dose-Escalation and Dose-Expansion Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics/Pharmacodynamics, and Antitumor Efficacy of Humanized Anti-PD-1 Monoclonal Antibody QL1604 in Patients with Advanced or Metastatic Solid Tumors."* This study is the first human trial of Aipalolimab, led by Professor Fan Yun's team from Zhejiang Cancer Hospital.

Epalrolizumab, a recombinant anti-PD-1 humanized monoclonal antibody developed by Qilu Pharmaceutical, has demonstrated good safety, tolerability, and pharmacokinetic (PK)/pharmacodynamic (PD) characteristics, as well as showing anti-tumor activity. These findings provide evidence for further clinical research on Epalrolizumab.

(Official website original text link:https://www.frontiersin.org/articles/10.3389/fimmu.2023.1258573/full ）

I.Research Background and Objectives

This study is an open-label, Phase I clinical trial of Emapalumab conducted in patients with advanced or metastatic solid tumors. The primary objective of the study is to observe the safety and tolerability of Emapalumab and determine the recommended dose for subsequent clinical trials.

2.Study Design and Patient Distribution

This study consists of two phases: dose escalation and dose expansion. From May 29, 2019, to July 24, 2020, a total of 35 patients were enrolled and received treatment with Aipalolizumab. As of the data cutoff date (July 14, 2022), four patients were still undergoing treatment.

3.Safety, Tolerability, and Efficacy Results

Among the 6 patients in the ipalimumab 3 mg/kg every 2 weeks (Q2W) group, one patient (16.7%) with thymic carcinoma experienced dose-limiting toxicity (DLT), which was grade 3 myasthenia gravis and immune-mediated myositis. No DLT occurred at the planned highest escalated dose of 10 mg/kg, thus no definitive maximum tolerated dose (MTD) was identified, and the drug was well-tolerated.

Adverse events (AEs) occurred in 94.3% (33/35) of patients, with 82.9% (29/35) being treatment-related adverse events (TRAEs). The safety profile was consistent with previously reported PD-1 monoclonal antibodies. The most common TRAEs (≥10%) were fatigue (37.1%), anemia (22.9%), increased thyroid-stimulating hormone (17.1%), elevated aspartate aminotransferase (AST) (17.1%), elevated alanine aminotransferase (ALT) (14.3%), decreased white blood cell count (11.4%), rash (14.3%), and pruritus (14.3%). Most TRAEs were grade 1 to 2. The incidence of grade 3 or higher TRAEs was 17.1% (6/35). No grade 5 TRAEs occurred.

A total of 17 patients (48.6%) experienced immune-related adverse events (irAEs), with the most common irAE being elevated thyroid-stimulating hormone (17.1%); 4 patients (11.4%) experienced grade 3 or higher irAEs, and 3 patients (8.6%) experienced infusion-related adverse events (all grade 1-2).

Safety data show that ipalimumab is safe and manageable, with no new safety signals observed.

A total of 7 patients (20.0%) achieved partial response (PR), and 5 patients (14.3%) achieved stable disease (SD). The objective response rate (ORR) was 20.0% (7/35), and the disease control rate (DCR) was 34.3% (12/35).. SlowThe median duration of response (DOR) for patients was 26.64 months (95% CI, 2.79-not evaluable).

4.Pharmacokinetics/Pharmacodynamics Results

Within the dose range of 0.3 mg/kg to 10 mg/kg, the half-life (T_1/2) is 3 to 11 days, and drug exposure is linearly related to the dose.

Pharmacodynamic results showed that after administration of Epalumab 3 mg/kg Q2W, 3 mg/kg Q3W, 10 mg/kg Q2W, and a fixed dose of 200 mg Q3W, the average receptor occupancy (RO) of PD-1 was greater than 80% within one treatment cycle.

5.Summary

Epalumab monotherapy demonstrated favorable safety and pharmacokinetic profiles in patients with advanced or metastatic solid tumors, showing clear signals of antitumor efficacy. The recommended doses for subsequent clinical studies were determined to be 3 mg/kg Q3W and a fixed dose of 200 mg Q3W.

The clinical study of Aipalolizumab for the treatment of patients with advanced solid tumors characterized by mismatch repair deficiency (dMMR) or high microsatellite instability (MSI-H), who have failed standard treatments and are unresectable or metastatic, has reached its primary endpoint. The new drug application was accepted by the Center for Drug Evaluation of the National Medical Products Administration on September 17, 2023.