▎WuXi AppTec Content Team Report

QL1706（Epalumab Injection is a bifunctional combination antibody developed by Qilu Pharmaceutical.，ByIgG4 Antibody Targeting PD-1Ipilimumab (iparomlimab）AndIgG1 Antibody Targeting CTLA-4Toripalimab (tuvonralimab）Composition.The product has a synergistic mechanism of simultaneously blocking PD-1 and CTLA-4, while reducing the toxicity caused by the CTLA-4 antibody. In August 2023,QL1706The first marketing application has been accepted by China NMPA forSecond-line treatment for recurrent or metastatic cervical cancer patients。

For the indication of first-line treatment of hepatocellular carcinoma, QL1706 has previously achieved positive results in a phase 1b/2 clinical study.This timeQL1706 in Combination with Bevacizumab (Bev) and/or ChemotherapyFirst-line treatment for advanced hepatocellular carcinoma (aHCC)A randomized, open-label, phase 2/3 study (DUBHE-H-308) was selected for LBA.

Patients were randomly assigned to four groups: Cohort 1: QL1706 (7.5mg/kg, Q3W) + bev (15 mg/kg, Q3W) + chemotherapy (aHCC regimen, i.e., oxaliplatin + capecitabine, Q3W, up to 4 cycles); Cohort 2: QL1706 + bev; Cohort 3: QL1706 + chemotherapy; Cohort 4: an approved anti-PD-1 monoclonal antibody + bev. The primary endpoints of this Phase 2 study include investigator-assessed objective response rate (ORR) per RECIST v1.1 and safety.

Screenshot source: ESMO Conference Official Website

A total of 120 patients were enrolled. As of the data cutoff date (July 12, 2024), the median follow-up time was 6.7 months. The ORR and DCR are shown in the table above. At this point, the progression-free survival (PFS) is not yet mature.The 6-month PFS for the above four groups of patients were 78.5%, 64.3%, 53.8%, and 50.3%, respectively.The incidence rates of treatment-related adverse events ≥ Grade 3 in the four groups were 46.7%, 50.0%, 46.7%, and 37.9%, respectively.

The researchers believe that in the Phase 2 portion of the DUBHE-H-308 study, QL1706+bev combined with chemotherapy demonstrated encouraging preliminary efficacy and manageable safety as a first-line treatment for aHCC.Independent Data Monitoring Committee Selects QL1706 + Bevacizumab (Bev) + Chemotherapy (XELOX) as the Future Phase 3 Study Regimen. In this cohort, the patient ORR was 35.5%, and the DCR was 87.1%.

References:

[1]ESMO Conference Official Website. Fromhttps://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/show/session/26

[2] More Effective and Safer! Qilu Pharmaceutical's Innovative Drug QL1706 for Cervical Cancer Treatment Presented at ESGO Conference Oral Report. Retrieved Mar 11 , 2024. From https://mp.weixin.qq.com/s/_ueTOgCz4Ym3vS-F2CEpsA