Iparomlimab and tuvonralimab (QL1706) plus chemotherapy and bevacizumab for EGFR-mutant patients with advanced non-small cell lung cancer after failure of EGFR-tyrosine kinase inhibitors: updated results from cohort 5 in the DUBHE-L-201 study

Iparomlimab and tuvonralimab (QL1706), a bifunctional anti-programmed death-1/cytotoxic T-lymphocyte antigen-4 antibody, in combination with bevacizumab and doublet chemotherapy was tolerable and showed preliminary antitumor activity in advanced non-small cell lung cancer (NSCLC) in DUBHE-L-201 study. Here, we report the updated data of long-term survival prognosis and safety from cohort 5. Epidermal growth factor receptor (EGFR)-mutant patients who progressed on EGFR-tyrosine kinase inhibitors (TKIs) were enrolled in cohort 5 and received QL1706 (5 mg/kg) combined with bevacizumab, pemetrexed and carboplatin in a three-week cycle for up to four cycles followed by maintenance therapy of QL1706, bevacizumab and pemetrexed. Survival outcomes and adverse events were followed up. As of July 5, 2024, the median duration of response, progression-free survival (PFS), and overall survival (OS) in the 31 patients in cohort 5 was 11.33 months (95% confidence interval [CI]: 4.17-19.91), 8.51 months (95% CI: 5.72-13.31), and 26.51 months (95% CI: 12.81-not reached), respectively. In 23 (74.2%) patients who received subsequent anticancer therapy after disease progression, the median PFS was 10.02 months. The median PFS (8.51 months vs. 5.95 months, P = 0.622) and median OS (30.19 months vs. 10.68 months, P = 0.177) appeared longer in patients with 21L858R mutation compared to those with 19Del, although the differences were not statistically significant. Grade ≥ 3 treatment-related adverse events occurred in 13 (41.9%) patients. Nineteen (61.3%) patients had immune-related adverse events, of whom one (3.2%) were grade ≥ 3. No new safety signal was observed. QL1706 combining pemetrexed, carboplatin, and bevacizumab showed long-term favorable prognosis and manageable safety profile for advanced EGFR-mutant patients with NSCLC after failure of EGFR-TKIs.