QL1706 (Eto Combination Antibody) Demonstrates Promising Efficacy and Manageable Safety in First-Line Advanced Renal Cell Carcinoma at ESMO 2025
Qilu Pharmaceutical
Specialty Formulations and Active Pharmaceutical Ingredients (API) Developer
During the 2025 European Society for Medical Oncology (ESMO) Congress, Qilu Pharmaceutical's Aipaloli Tovorali Monoclonal Antibody (QL1706, Qibean).®, referred to as "Aituo Combination Antibody") has been successfully selected for research in the field of renal cell carcinoma. As the world’s first approved PD-1/CTLA-4 bifunctional combination antibody, it achieves a 2:1 synergistic inhibition of the PD-1 and CTLA-4 targets through the MabPair antibody engineering technology. It has demonstrated clinical value in cancer types such as cervical cancer, liver cancer, and lung cancer, becoming a recommended drug in authoritative guidelines within the field.1The unveiling of this renal cell carcinoma (RCC) research data not only marks a significant advancement in its cross-cancer type strategy but also provides a new direction for the first-line treatment of advanced kidney cancer. This article will briefly analyze the research value and prospects of the Aito combination antibody in this field based on the latest research progress from the ESMO conference and the current state of kidney cancer treatment.
Unmet Clinical Needs:Current Status and Clinical Needs of RCC Treatment
RCC accounts for approximately 80%-90% of renal malignant tumors. The treatment has evolved from traditional cytokine therapy and anti-angiogenic targeted therapy to the current stage of immunotherapy combined with targeted-immunotherapy. At present, the combination of targeted therapy and immunotherapy has become the main treatment option for intermediate- to high-risk advanced patients.2, but in clinical practice, multiple challenges remain: Non-clear cell renal cell carcinoma (nccRCC) has limited efficacy with existing treatment options due to strong molecular heterogeneity; some patients cannot tolerate standard treatment because of immune-related adverse events (irAEs); the survival improvement needs of high-risk patients have not been fully met, and so on.
ESMO Research Overview: Phase Ib Exploratory Results Reveal the Potential of Aito Combination Antibody in Treating Advanced RCC
The study selected for ESMO this time is a single-arm, multi-center Phase Ib clinical trial (Abstract No.: 2602P), aimed at evaluating the safety and preliminary efficacy of the Aito combination antibody plus lenvatinib in patients with advanced RCC. Enrolled patients received 5.0 mg of Aito combination antibody (D1) + 20 mg lenvatinib (D1-D21). The study included a total of 33 patients with locally advanced or metastatic clear cell renal carcinoma who had not previously received systemic treatment, with a median age of 57.0 years.
As of February 1, 2025, the median follow-up was 22.0 months. The incidence of treatment-related adverse events (TRAEs) was 97.0% (32/33), with a ≥3 grade TRAE rate of 75.8% (25/32). Notably, the most common ≥3 grade TRAE was hypertension (39.4%), which is primarily a known toxicity of lenvatinib and is clinically well-managed. Six patients discontinued treatment due to TRAEs.
Notably, the dose exploration results showed that no dose-limiting toxicity (DLT) events occurred, and the dose of the Aito combination antibody was not reduced.
Due to the early impact of the COVID-19 pandemic, the data integrity of the first 13 enrolled patients was poor or follow-ups were not conducted in a timely manner (several cases were terminated/withdrawn prematurely). Therefore, this analysis also includes the 20 subjects enrolled after the end of the pandemic.
Among 20 evaluable patients,Objective Response Rate (ORR) Reached 75.0%(95% CI 50.9%~91.3%), with one patient achieving complete remission (CR).Disease Control Rate (DCR) was 90.0%(95% CI 68.3%~98.8%), median duration of response (DoR), PFS, and OS have not yet been reached.The 22-month PFS rate was 54.4%.（95% CI 26.9%~75.3%）。The safety data of the subgroup were consistent with the overall population.
The study showed that the combination of Atezolizumab and Lenvatinib demonstrated good tolerability, manageable safety, and promising anti-tumor activity in first-line treatment for advanced RCC, indicating the potential of this combination therapy for such patient populations. Further exploration of this combination regimen is currently being planned.
In-Depth Analysis of the Mechanism: The Principle of Dual-Target Synergy
The mechanism of action of the Aito combination antibody is based on a dual-target synergistic design: inhibition of the PD-1 pathway can release the "immune brake" on T cells, restoring the ability of effector T cells to recognize and kill tumor cells; blockade of the CTLA-4 pathway can promote T cell activation and proliferation, enhancing the immune response. As an "immunogenic tumor," renal cell carcinoma contains a large number of immunosuppressive cells in the tumor microenvironment, and dual-target blockade may more thoroughly reshape the immune microenvironment.
Preclinical studies have shown3，The antitumor activity of the Aito combination antibody is improved compared to PD-1 monoclonal antibody or CTLA-4 monoclonal antibody. Additionally, by optimizing the Fc segment structure, the Aito combination antibody can enhance safety and reduce the occurrence of irAEs. When combined with lenvatinib treatment, the anti-angiogenic effect of the VEGFR inhibitor can improve blood perfusion in the tumor microenvironment, promote antibody drug delivery, and create a synergistic effect.
Conclusion
The Phase Ib study data of Aito combination antibody for renal cell carcinoma presented at the ESMO conference demonstrated its potential efficacy and safety in the treatment of advanced renal cell carcinoma. As a bifunctional combination antibody, it offers a new direction for clinical exploration in the field of renal cell carcinoma treatment, where combination therapies involving targeted agents and immunotherapy are mainstream. Multiple clinical studies of Aito combination antibody in renal cell carcinoma are currently underway, which may further clarify its value in renal cell carcinoma treatment. If approved for renal cell carcinoma indication in China in the future, it is expected to complement existing therapies and enhance the renal cell carcinoma treatment system.
References:
1. Guidelines Working Committee of Chinese Society of Clinical Oncology. "CSCO Clinical Application Guidelines for Immune Checkpoint Inhibitors 2025"
2. "Chinese Society of Clinical Oncology (CSCO) Renal Cell Carcinoma Diagnosis and Treatment Guidelines (2025)"
3. Zhao Y, et al. J Hematol Oncol. 2023;16(1):50.
Approval Number
NP202510150003-valid until 202610