Iparomlimab Yields Responses in dMMR/MSI-H Metastatic Solid Tumors

In a single-arm, phase 2 trial, patients received iparomlimab at 200 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, subsequent line of therapy, withdrawal of consent, or death.

Iparomlimab (QL1604) demonstrated efficacy and produced responses in patients with unresectable or metastatic mismatch repair deficient (dMMR)/microsatellite instability–high (MSI-H) solid tumors, according to a press release on findings from a phase 2 trial (NCT04326829).¹

Data from the trial, which investigators presented at the European Society for Medical Oncology (ESMO) Asia Congress 2023, highlighted complete responses (CRs) in 11 patients and partial responses (PRs) in 44 after a median follow up of 13.6 months, yielding an objective response rate (ORR) of 45.8% (95% CI, 36.7%-55.2%).² Additionally, investigators reported a disease control rate (DCR) of 77.5% (95% CI, 69.0%-84.6%). In a cohort of patients with colorectal cancer (CRC), the ORR and DCR, respectively, waswere 42.5% (95% CI, 31.5%-54.1%) and 77.5% (95% CI, 66.8%-86.1%).

Investigators reported that the median duration of response (DOR) was not reached at the time of the analysis; the DOR rate was 100% (95% CI, not estimable [NE]-NE) at 6 months and 97.4% (95% CI, 83.2%-99.6%) at 12 months. The median overall survival (OS) and progression-free survival (PFS) were not yet reached.

The most common treatment-related adverse effect (TRAE) was anemia; any-grade and grade 3 or higher toxicity of this kind occurred in 25.8% and 5.0% of patients, respectively. Investigators observed no patient deaths related to study treatment.Treatment-emergent adverse effects (TEAEs) of any grade occurred in 97.5% of patients.

In the single-arm, phase 2 trial, patients received iparomlimab at 200 mg intravenously every 3 weeks until disease progression, unacceptable toxicity, subsequent line of therapy, withdrawal of consent, or death. Patients received study treatment for up to 2 years and were then followed up for survival.

The study’s primary end point was ORR as determined via independent radiological review committee based on RECIST v1.1 criteria. Secondary end points included OS, PFS, and DOR.

Investigators enrolled a total of 120 patients with dMMR/MSI-H solid tumors between June 2020 and January 2023. Most patients had CRC (66.7%) followed by other solid tumors (18.3%) and gastric cancer (15.0%). Additionally, most had stage IV disease (97.5%). Patients also received a median of 2.0 (range, 0-6) prior lines of therapy.

Patients between the ages of 18 years and older but no older thanand 80 with histologically confirmed locally advanced or metastatic CRC or other malignant solid tumors that were dMMR/MSI-H were able to enroll on the trial. Additional eligibility criteria included having at least 1 measurable lesion based on RECIST v1.1 guidelines, disease progression following prior standard anti-cancer therapy, an ECOG performance status of 0 or 1, a life expectancy of more than 12 weeks, and adequate hematologic and organ function. Patients were also required to have available tumor tissue and blood samples for assessment of MSI, tumor mutational burden, and PD-L1 expression.

Those with central nervous system metastases, autoimmune disease that needed to be managed with systemic therapy within 2 years of entry, or major cardiovascular and cerebrovascular diseases were unable to enroll on the study. Patients were also unsuitable for enrollment if they had uncontrollable pleural effusion, any condition requiring management with corticosteroids, or received any live vaccine within 30 days of beginning study treatment.

References

1. Qilu Pharmaceutical announces results from phase II study for iparomlimab for advanced solid tumors at ESMO Asia, with an ORR of 45.8%. News release. Qilu Pharmaceutical Co., Ltd. December 6, 2023. Accessed December 6, 2023. https://prn.to/3NgfEG9
2. Guo W, Bi F, Dong J, et al. A single-arm, phase II, multicenter study of iparomlimab (QL1604) in patients (pts) with unresectable/metastatic deficient mismatch repair (dMMR)/microsatellite instability high (MSI-H) solid tumors. Ann Oncol. 2023;34(suppl 4):S1502-S1519. doi:10.1016/j.annonc.2023.10.240