Qilu Pharmaceutical Announces Results from Phase II Study for iparomlimab for Advanced Solid Tumors at ESMO Asia, with an ORR of 45.8%

JINAN, China, Dec. 6, 2023 /PRNewswire/ -- Qilu Pharmaceutical presented the latest results of the single-arm, phase II pivotal clinical study for iparomlimab (QL1604), an innovative Class 1 antibody monotherapy used to treat unresectable or metastatic dMMR/MSI-H solid tumors through a poster presentation at the European Society for Medical Oncology Asia Congress 2023 (ESMO Asia) taken place from December 1-3. Professor Weijian Guo from the Fudan University Shanghai Cancer Center and Professor Feng Bi from the West China Hospital, Sichuan University led the study.

QL1604 is a highly selective humanized monoclonal antibody that targets PD-1. The study demonstrated that iparomlimab was effective in treating unresectable or metastatic dMMR/MSI-H solid tumors, with an objective response rate (ORR) of 45.8% (95% CI, 36.7-55.2) in total population as assessed by the Independent Imaging Review Committee (IRRC), exceeding the prespecified primary study endpoint.

I. Background

The presence of defective DNA mismatch repair (dMMR) or high microsatellite instability (MSI-H) signifies a unique phenotype in solid tumors ^[1]. Microsatellite sequences are most susceptible to mismatches during DNA replication and require mismatch repair, and dMMR can lead to code-shifting mutations causing microsatellite instability (MSI). Immune checkpoint inhibitors have proven to be effective in treating dMMR/MSI-H solid tumors. Treatment of dMMR/MSI-H solid tumors with programmed death receptor-1 (PD-1) or programmed death ligand-1 (PD-L1) inhibitors results in a high objective response rate (ORR) and a long duration of response ^[2-3].

Phase I study showed that iparomlimab has demonstrated good safety and anti-tumor activity when treating advanced solid tumors, with an ORR of 20% in all patients who received iparomlimab (0.3-3 mg/kg Q3W) ^[4]. The objectives of this pivotal study were to evaluate the efficacy and safety of iparomlimab in the treatment of unresectable or metastatic dMMR/MSI-H solid tumors.

II.Study Design and Methods

This single-arm, phase II pivotal clinical study enrolled patients with unresectable or metastatic histopathologically or cytologically confirmed dMMR/MSI-H solid tumors. Iparomlimab was administered intravenously at a fixed dose of 200mg (or 3mg/kg for patients under 40kg) every three weeks. Treatment continued until disease progression, intolerable toxicities, initiation of new anti-tumor treatment, death, withdrawal of informed consent, or other reasons, with a maximum treatment duration of 2 years. At the end of treatment, patients were followed up for survival. The primary endpoint of the study was ORR as assessed by IRRC according to the Response Evaluation Criteria in Solid Tumors (RECIST) (Version 1.1). 

III. Results

From June 2020 to January 2023, 120 patients with dMMR/MSI-H solid tumors were enrolled, including 80 (66.7%) with colorectal cancer, 18 (15.0%) with gastric cancer, and 22 (18.3%) with other solid tumors. The majority (97.5%) were stage IV at enrollment. The median number of treatment lines was 2.0 (range 0-6).

As of 20 July 2023, after a median follow-up of 13.6 months, 11 patients achieved complete response (CR) and 44 patients achieved partial response (PR), resulting in an ORR of 45.8% (95% CI: 36.7%-55.2%) and a disease control rate (DCR) of 77.5% (95% CI. 69.0%-84.6%). In patients with colorectal cancer, the ORR and DCR were 42.5% (95% CI: 31.5%-54.1%) and 77.5% (95% CI: 31.5%-54.1%), respectively. Median duration of response (DoR) was not yet reached, with 6- and 12-month DoR rates of 100% and 97.4%, respectively. Median progression-free survival (PFS) and median overall survival (OS) were yet to be reached. 

IV. Summary

Iparomlimab monotherapy showed good efficacy and safety in treating unresectable or metastatic dMMR/MSI-H solid tumors. The new drug application of iparomlimab was accepted by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA) in September 2023.