The European Society for Medical Oncology Asia (ESMO Asia) Congress was held in Singapore，from 6 to 8 December 2024. ESMO Asia is an annual congress specifically focused on multidisciplinary oncology in the Asian region, providing a remarkable platform for participants to share and discuss the latest research findings, clinical trials, and treatment strategies in the field. During the three-day event, Qilu Pharmaceutical unveiled the latest findings from three key studies on iparomlimab and tuvonralimab (QL1706), a bifunctional MabPair® product of anti-PD-1 IgG4 and anti-CTLA-4 IgG1 antibodies.1. Cervical Cancer: DUBHE-C-204 Study
The latest Phase II data on Iparomlimab and tuvonralimab (QL1706), as a first-line treatment for patients with recurrent or metastatic cervical cancer was presented as a proffered oral presentation at the conference[1].
This open-label, non-randomized, multicenter Phase II study aimed to evaluate the safety and efficacy of QL1706 in combination with chemotherapy, with or without bevacizumab. The study divided participants into two cohorts. Cohort 1 patients received QL1706 with paclitaxel and cisplatin/carboplatin, while Cohort 2 patients received QL1706 plus chemotherapy and bevacizumab to the same regimen. After six cycles, maintenance treatment with QL1706 ± bevacizumab continued until disease progression, unacceptable toxicity, or other discontinuation criteria. The primary endpoint was safety, while secondary endpoints included efficacy measures.
The 2023 ESMO Congress revealed promising data from a 14-month follow-up[2], demonstrating manageable safety and encouraging efficacy. At ESMO Asia 2024, extended follow-up results (27 months, data cutoff June 25, 2024) were presented. Among 58 evaluable patients, the objective response rate (ORR) was 81.0%, the disease control rate (DCR) was 98.3%, and the median progression-free survival (PFS) was 15.1 months, with median overall survival (OS) not yet reached.
Safety
Treatment-related adverse events (TRAEs):Grade ≥3 TRAEs occurred in 45 patients (75.0%), with the most common being neutropenia (38.3%), leukopenia (33.3%), and lymphopenia (18.3%).
Severe adverse events:Treatment-related serious adverse events (TRSAEs), discontinuation due to TRAEs, and grade ≥3 immune-related adverse events occurred in 36.7%, 31.7%, and 15.0% of patients, respectively.
These results support further investigation, paving the way for the Phase III DUBHE-C-301 study, which aims to confirm the efficacy of QL1706 in this setting.
2. Lung Cancer: DUBHE-L-201 Study
Iparomlimab and tuvonralimab (QL1706) is a bifunctional MabPair® product combining anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies. It represents a novel strategy to address resistance mechanisms to EGFR tyrosine kinase inhibitors (TKIs).
In Phase I studies[3], QL1706 monotherapy demonstrated an objective response rate (ORR) of 24.2% in advanced non-small cell lung cancer (NSCLC) patients without prior immunotherapy. Building on these results, the Phase II DUBHE-L-201 study cohort 5 is evaluating the efficacy of QL1706 combined with chemotherapy and bevacizumab in patients with EGFR-TKI resistance.
Preliminary data on ORR and PFS were published in Signal Transduction and Targeted Therapyin January 2024[4]. Updated OS data was presented as a poster at ESMO Asia 2024[5], with the following results:
ORR: 54.8%
Median PFS: 8.5 months
Median OS: 26.5 months
These findings highlight the potential of QL1706 in providing sustained immunotherapy benefits for EGFR-TKI-resistant NSCLC patients.
3. Metastatic Colorectal Cancer: DUBHE-C-208 Study (Best Poster Award)
QL1706 also demonstrated significant efficacy in metastatic colorectal cancer (mCRC), earning the Best Poster Award at ESMO Asia 2024[6].
This multicenter single-arm phase II trial (clinicaltrials.gov: NCT05799820) recruited treatment-naïve patients with unresectable locally advanced or mCRC. Participants were divided into two cohorts:
Cohort 1:Patients with MSI-high tumors regardless of RAS/BRAF status were recruited and administered monotherapy of QL1706 at 5 mg/kg intravenously every three weeks (Q3W).
Cohort 2:Wild-type RAS/BRAF patients with MSS/MSI-low tumors were recruited and administered combined therapy of 5 mg/kg QL1706, 7.5mg/kg bevacizumab, and XELOX Q3W.
Key Findings (as of April 15, 2024)
Cohort 1:
ORR: 62.5%
DCR: 100%
Median duration of response (DoR): Not reached (12-month DoR rate: 100%).
Cohort 2:
ORR: 70.6%
DCR: 96.1%
Median DoR: Not reached.
Safety
lCohort 1: 2 (25.0%) patients experienced TRAEs of grade ≥3.
lCohort 2: 35 (68.6%) patients experienced TRAEs of grade ≥3 (54.9% chemotherapy-related), with neutrophil count decreased as the most common.
Both cohorts showed manageable safety profiles with no new safety signals, supporting the exploration of QL1706 as the first-line treatment for mCRC.
Conclusion
QL1706 showed sustainable response in patients with MSI-high mCRC. QL1706-combined therapy showed high ORR and tolerability in patients with MSS/MSI-low mCRC. No new safety signal was observed with QL1706 or its combined therapy. The efficacy of QL1706-combined therapy in patients with MSS/MSI-low mCRC warrants further exploration.
References:
[1] 2024 ESMO Asia Presentation Number: 373O.
[2] 2023 ESMO Presentation Number: 743MO.
[3] Zhao Y, et al. J Hematol Oncol. 2023 May 8;16(1):50.
[4] Huang Y, et al. Signal Transduct Target Ther. 2024 Jan 29;9(1):23.
[5] 2024 ESMO Asia FPN: 646P.
[6] 2024 ESMO Asia FPN: 77P.
