QL1706 (Aitolimab-Tuvonralimab) Combination Antibody Demonstrates Promising Efficacy and Safety in First-Line Unresectable Hepatocellular Carcinoma: Updated Results from the DUBHE-H-106 Study Presented at ASCO GI 2025

Jan 25, 2025 20:27 CST Updated 20:27

Qilu Pharmaceutical

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The 2025 American Society of Clinical Oncology Gastrointestinal Cancers Symposium (2025 ASCO GI) was held in San Francisco, USA, from January 23 to 25 local time. This conference adopted a combination of online and offline formats, bringing together top experts in the field of gastrointestinal oncology from around the world to share the latest research findings and discuss cutting-edge academic trends.

In the field of immunotherapy for advanced liver cancer, this time Many studies presented at the ASCO GI Conference have brought new insights to clinical practice. Among them, the study led byProfessor Bi Feng from West China Hospital, Sichuan UniversityLed by DUBHE-H-106 Study Draws Significant Attention: Updated Results of the Phase Ib/II Clinical Trial Evaluating Aipalolitovorelizumab (QL1706, Abbreviated as Aito Combination Antibody) or Aipalolizumab (QL1604) in Combination with Bevacizumab as First-Line Treatment for Unresectable Hepatocellular Carcinoma (HCC) Reinforce the Excellent Efficacy and Safety of the Aito Combination Antibody Therapy^[1]. This achievement has not only attracted widespread attention from scholars both in China and internationally, but also highlighted China's strong capabilities in the field of clinical oncology research. It has contributed Chinese wisdom to the global field of cancer treatment, and also provided new options for patients with advanced HCC First-line Treatment Opens New Pathways.

DUBHE-H-106 Study Shines at ASCO GI, Innovative Combination Antibody Achieves New Breakthrough

The Aito combination antibody was developed by Qilu Pharmaceutical using MabPair.^®The world's first bi-functional combination antibody developed on a biotechnology platform, consisting of a recombinant humanized IgG4 monoclonal antibody targeting human PD-1 and a recombinant humanized IgG1 monoclonal antibody targeting human CTLA-4. In the previously released preliminary data from the DUBHE-H-106 study, the combination of Aito antibodies with bevacizumab for first-line treatment of advanced HCC has demonstrated encouraging efficacy and safety.^[2]. This ASCO GI conference reported the updated results of the DUBHE-H-106 study.^[1]。

DUBHE-H-106 study enrolled patients aged ≥18 years with histologically or clinically confirmed unresectable HCC, who had not received prior systemic treatment, and had at least one measurable untreated lesion according to RECIST v1.1 criteria, ECOG performance status score of 0-1, Child-Pugh score ≤7, Barcelona Clinic Liver Cancer (BCLC) stage B-C, and an expected survival time ≥3 months.

The patients enrolled in the study were divided into the following three cohorts:

▶Cohort A: Aituo combination antibody 5 mg/kg + Bevacizumab, once every 3 weeks

▶Cohort B: QL1604 200 mg + Bevacizumab, once every 3 weeks

▶Cohort C: Aito Combination Antibody 7.5 mg/kg + Bevacizumab, once every 3 weeks

The primary endpoint was safety; secondary endpoints included objective response rate (ORR), disease control rate (DCR), progression-free survival (PFS), etc.

Figure 1. DUBHE-H-106 Study Design

The research results showed that from June 2021 to December 2023, Cohorts A, B, and C included 50, 26, and 40 patients, respectively, for safety analysis. No dose-limiting toxicity (DLT) was reported, and the types and incidence of adverse events (AE) were similar across the cohorts. Moreover,The incidence of ≥ Grade 3 treatment-related adverse events (TRAEs, 48% vs 40%), serious TRAEs (22% vs 25%), and immune-related adverse events (irAEs, 54% vs 55%) was similar between Cohort A and Cohort C, suggesting that the use of the Etotolimod combination antibody at a dose of 7.5 mg/kg did not increase the overall occurrence of AEs.

Table 1. Safety Results of DUBHE-H-106 Study

Cohorts A, B, and C included 47, 26, and 37 patients, respectively, for efficacy analysis. Among themCohort C Showed the Best Efficacy:

▶ORR：43%（95%CI 27%–61%）

▶DCR：81%（95%CI 65%–92%）

▶Median PFS: 7.0 months (95% CI 4.2–NE)

▶12-Month PFS Rate: 40.9% (95% CI 24.3%–56.9%)

In addition, the efficacy of Cohort A was better than that of Cohort B, with ORR rates of 38% and 23%, DCR rates reaching 74% and 69%, median PFS of 7.0 months and 5.4 months, and 12-month PFS rates of 26.8% and 24.4%, respectively.

Table 2. Efficacy Results of DUBHE-H-106 Study

DUBHE-H-106 study results show that the combination of Aito antibodies or QL1604 with bevacizumab as first-line treatment for unresectable HCC has acceptable toxicity and encouraging efficacy.EspeciallyAito Combination Antibody7.5 mg/kg combined with bevacizumab not only demonstrates stronger anti-tumor activity but also maintains good safety.

HCC Immunotherapy Era: Aito Combination Antibody Shows Unlimited Clinical Potential

Immune checkpoint inhibitors have brought revolutionary changes to the treatment of advanced HCC. However, the efficacy benefits of traditional immune checkpoint inhibitors as first-line treatment for advanced HCC remain limited, with ORR typically below 30% and median PFS less than half a year.^[3-6]The combination of dual immunotherapy is a hot direction in the current field of oncology, but the combination of multiple drugs may affect clinical convenience and patient compliance. The emergence of Aituo bispecific antibody, as a new type of dual-target immune drug, provides an innovative solution to this problem.

In early preclinical and clinical studies, the combination of Aito antibodies has preliminarily demonstrated its efficacy and safety.Among them, the Phase I study enrolled a total of 518 patients with advanced solid tumors. The results showed that the Aito combination antibody had definitive efficacy in monotherapy for various solid tumors as a last-line treatment, with a good safety profile.^[7]Preliminary results of the DUBHE-H-106 study presented at the 2023 American Society of Clinical Oncology (ASCO) showed that the combination of Aito antibodies with bevacizumab performed excellently as a first-line treatment for advanced HCC, offering a promising new therapeutic option for patients with advanced HCC.^[2]。

The latest data from the DUBHE-H-106 study was presented at this year's ASCO GI conference, revealing thatThe combination regimen of Aituo antibody 7.5 mg/kg + Bevacizumab demonstrated superior efficacy, with an ORR of 43%, DCR reaching 81%, median PFS of 7.0 months, and a 12-month PFS rate of 40.9%. This regimen also exhibited good safety without increasing the incidence of overall AEs.。Therefore, the dose of 7.5 mg/kg for the Aito combination antibody is recommended for application in future clinical studies.

It is worth noting that,The efficacy and safety results of the 7.5 mg/kg combination antibody therapy with Aito are consistent with the findings from the Phase II/III DUBHE-H-308 study.。DUBHE-H-308 Study Aims to Explore the Efficacy and Safety of Aito Combination Antibody + Bevacizumab ± Chemotherapy as First-Line Treatment for Advanced HCC, with Aito Combination Antibody Administered at a Dose of 7.5 mg/kg. The Phase II results of this study, presented at the 2024 European Society for Medical Oncology (ESMO) Congress, showed that the experimental groups (including Aito Combination Antibody + Bevacizumab + Chemotherapy, Aito Combination Antibody + Bevacizumab, Aito Combination Antibody + Chemotherapy) achieved higher ORR (38.7%, 43.3%, 46.7% vs 27.6%), DCR (87.1%, 80.0%, 86.7% vs 72.4%), median PFS (NR, 8.1 months, 7.0 months vs 5.9 months), and 6-month PFS rates (79.0%, 64.3%, 57.7% vs 49.5%) compared to the control group (Sintilimab + Bevacizumab). The incidence of ≥Grade 3 TRAEs was similar between the experimental and control groups (46.7%, 53.3%, 56.7% vs 44.8%).^[8]Currently, the Phase III stage of the DUBHE-H-308 study is enrolling participants, and we look forward to the announcement of its results.

Exciting Update: DUBHE-H-106 Hepatocellular Carcinoma Data Interpretation Session to Be Held Soon

To further explore the clinical treatment potential of this innovative drug, keep up with the latest research trends, explore more treatment options, and grasp new advances in liver cancer treatment,2January 26, 2025, 11:30~12:30, "Bidding Farewell to the Old and Welcoming the New, Polaris Shines at ASCO-GI — DUBHE-H-106 Hepatocellular Carcinoma Data Update Interpretation Meeting" Will Be Held OnlineThis meeting boasts a gathering of top experts, including an invitation to Zhongshan Hospital Affiliated with Fudan University.Academician Fan JiaThe First Affiliated Hospital of China Pharmaceutical University (Nanjing Tianyin Mountain Hospital)Professor Shukui QinServed as the conference chair,Professor Bi FengServe as the conference host. At that time, the Tumor Hospital Affiliated to Harbin Medical UniversityProfessor Zhang Yanqiao, Peking University Cancer HospitalProfessor Zhou Junand Nanfang Hospital, Southern Medical UniversityProfessor Chen JinzhangMultiple experts in the field of liver cancer will gather online to provide a detailed interpretation of the DUBHE-H-106 study data, share their profound insights, and analyze the latest achievements and future trends in liver cancer treatment.

We sincerely invite you to participate in this academic conference in the field of liver cancer, and witness the new breakthrough of Chinese innovative drugs on the international stage.

✩ This article is intended for reference by medical and healthcare professionals only.

Content Planning: nyh

Project Review: Yu Xuan

ReferenceContribution:

[1]Bi F, et al. JCO. 2023;41(16_suppl):4077.

[2]Bi F, et al. 2025 ASCO-GI. Abstract #579.

[3]Finn R S, et al. N Engl J Med, 2020, 382(20): 1894-1905

[4]Z. Ren, et al. ESMO Asia Virtual Congress 2020. Abstract # LBA2.

[5]Arndt Vogel, et al. 2024 ASCO. Abstract # 4110.

[6]Finn RS, et al.IMbrave150 2021 ASCO-GI. Abstract # 267.

[7]Zhao Y, et al. J Hematol Oncol. 2023 May 8;16(1):50.

[8]Shukui Qin, et al. 2024 ESMO. Abstract # LBA 38.