QL1706 (Iparomlimab and Tuvonralimab) Combined with Bevacizumab and Chemotherapy Demonstrates Promising Efficacy and Manageable Safety in First-Line Advanced Hepatocellular Carcinoma: Phase 2 Results from the DUBHE-H-308 Study
Qilu Pharmaceutical
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The 2024 ESMO Annual Meeting will open on September 13 local time. At this year's conference, Qilu PharmaceuticalQL1706 in Combination with Bevacizumab and/or ChemotherapyUsed forFirst-line Treatment for Advanced Hepatocellular CarcinomaThe phase 2/3 study was selected for LBA. Data showed that QL1706 + bevacizumab combined with chemotherapy had good antitumor activity and safety as first-line treatment for advanced hepatocellular carcinoma.
Screenshot source:ESMO Official Website
QL1706 is a drug developed by Qilu Pharmaceutical based on the MabPair bispecific antibody technology platform.PD-1/CTLA-4 Combination Antibody, byPD-1 Antibody Aipalolizumab(Iparomlimab) andCTLA-4 Antibody Tovorali Monoclonal Antibody(Tuvonralimab) Composition.Previously, in the Phase 1b/2 study, QL1706 combined with bevacizumab for first-line treatment of advanced hepatocellular carcinoma demonstrated promising anti-tumor activity and favorable safety.
Selected for the LBA of this year's conference is a randomized, open-label Phase II/III study (DUBHE-H-308) ofPhase II Study Section, aiming to evaluate the efficacy and safety of QL1706 in combination with bevacizumab and/or chemotherapy for first-line treatment of advanced hepatocellular carcinoma.The primary endpoints of this Phase 2 study include ORR as determined by the investigator according to RECIST v1.1 and safety.。
In this study, patients were randomly assigned (1:1:1:1) to the following four groups:
Group 1, QL1706 (7.5 mg/kg, Q3W) + Bevacizumab (15 mg/kg, Q3W) + Chemotherapy (aHCC regimen, i.e., Oxaliplatin 85 mg/m2+Capecitabine 1000 mg/m2`, Q3W, up to 4 cycles`)；
Group 2, QL1706 + Bevacizumab;
Group 3, QL1706 + Chemotherapy;
Group 4, PD-1 antibody Sintilimab (200 mg, Q3W) + Bevacizumab.
The study enrolled a total of 120 patients. As of the data cutoff date (July 12, 2024), the median follow-up time was 6.7 months. The baseline characteristics of the four groups were roughly balanced. The data shows:
In terms of ORR, from Group 1 to Group 4 were 35.5%, 36.7%, 36.7%, and 13.8%, respectively.
In terms of DCR, from Group 1 to Group 4 were 87.1%, 80.0%, 86.7%, and 72.4%, respectively.
Progression-Free Survival (PFS) is not yet mature.6-Month PFS Rate, from Group 1 to Group 4 were 78.5%, 64.3%, 53.8%, and 50.3%, respectively.
Grade ≥3 treatment-related AEs occurred in 46.7%, 50.0%, 46.7%, and 37.9% of patients in the four groups, respectively. In Group 4, one patient died due to treatment-related hepatic failure.
Screenshot source:Insight Database
The study suggests that in the Phase II part of the DUBHE-H-308 study, QL1706 + bevacizumab combined with chemotherapy showed encouraging preliminary efficacy and manageable safety in first-line treatment for advanced hepatocellular carcinoma. Among them, Group 1QL1706 + Bevacizumab + XELOX ChemotherapyPlan(Oxaliplatin + Capecitabine) has been selected by the Independent Data Monitoring Committee as the experimental group for future Phase III studies.
Insight DatabaseIt shows that, currently in China, there are quite a few companies exploring the effects of dual-target therapy targeting PD-1 and CTLA-4 for the treatment of hepatocellular carcinoma. Among them,The fastest progressing is Kangfang's PD-1/CTLA-4 bispecific antibody Cadonilimab, which has entered Phase III stage.; Secondly,Qilu's PD-1/CTLA-4 Combination Antibody QL1706, Phase Ⅱ/ Ⅲ Phase research. Others entering the clinical stage for liver cancer indications includeAstraZeneca'sPD-1/CTLA-4 DualAnti-Vosumab(Phase II),Merck's Pembrolizumab ( PD-1 Monoclonal Antibody）+ Zivolib (CTLA-4 Monoclonal Antibody) Combination Therapy(Phase II）。
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