Abstract 646P
Background
EGFRi are the standard of care for EGFR-mutant advanced NSCLC. However, treatment options after progression remain limited. QL1706 is a bifunctional MabPair product containing anti-programmed cell death protein 1 (PD-1) and anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4) antibodies. The safety and efficacy of QL1706 for EGFRi-resistant advanced NSCLC have been previously published. Here, we report the updated results.
Methods
This phase II study included five cohorts of NSCLC patients. Key inclusion criteria of Cohort 5 (EGFRi-resistant cohort) were age ≥18 years; EGFR-mutant non-squamous NSCLC at stage IIIB/C or IV; progression on or intolerance to prior EGFRi treatment; and ≥one target lesion per RECIST v1.1. QL1706 (5 mg/kg), carboplatin (AUC 5–6), pemetrexed (500 mg/m2), and bevacizumab (15 mg/kg) were administered intravenously on day 1 of a 21-day cycle for four cycles. Maintenance treatment included QL1706, pemetrexed, and bevacizumab. The primary endpoint was safety. Secondary endpoints included investigator-assessed confirmed objective response rate (ORR), duration of response (DoR), progression-free survival (PFS), overall survival (OS), etc.
Results
Cohort 5 included 31 patients. As of data cutoff on May 31, 2024, median follow-up was 29.5 months. Incidences of treatment-related adverse events (TRAEs) slightly increased due to longer follow-up. Grade ≥3 TRAEs, grade ≥3 immune-related adverse events, any grade serious TRAEs, and any grade TRAEs leading to study treatment discontinuation occurred in 13 (41.9%), one (3.2%), 11 (35.5%), and two (6.5%) patients, respectively. Identical to previous report, 17 patients achieved an objective response (ORR 54.8%, 95% CI 36.0%–72.7%). Updated median DoR, PFS, and OS, were 11.3 (95% CI 4.2–19.9), 8.5 (5.7–13.3), and 26.5 months (12.8–not evaluable), respectively.
Conclusions
Iparomlimab and tuvonralimab plus chemotherapy and bevacizumab showed acceptable toxicity and remarkable efficacy for EGFRi-resistant EGFR-mutant advanced NSCLC. This regimen may be a new treatment option. Further studies are warranted.
Clinical trial identification
NCT05329025.
Editorial acknowledgement
We thank Yunjie Yu (Qilu Pharmaceutical Co., Ltd., Jinan, China) for providing medical writing support.
Legal entity responsible for the study
Sun Yat-sen University Cancer Center.
Funding
Qilu Pharmaceutical Co., Ltd. (Jinan, China) and Chinese National Natural Science Foundation Project (82241232, 82272789, 82173101, and 82373262).
Disclosure
H. Li, T. Wu, S. Xue, X. Kang: Financial Interests, Personal, Full or part-time Employment: Qilu Pharmaceutical Co., Ltd. All other authors have declared no conflicts of interest.