Mini oral 3: NSCLC metastatic

Prof Mariana Brandão, medical oncologist at the Institut Jules Bordet in Brussels shares a selection of studies presented during the mini oral session of NSCLC that she had the honour to chair and to be one of the discussants. 

The DEDICATION-1 trial, a non-inferiority study from the Netherlands, aims to optimize pembrolizumab dosing for advanced NSCLC. Previous studies demonstrated that varying doses of pembrolizumab (2 mg/kg vs. 10 mg/kg) delivered similar response rates, PFS and OS. This led to the current flat dose of 200 mg every three weeks, which may represent overtreatment. In DEDICATION-1, researchers compared 200 mg every six weeks to 100 mg every three weeks. Interim results showed only a 2.7% difference in one-year OS, with similar PFS between dosing schedules. If these results hold, reduced dosing could significantly lower treatment costs without compromising efficacy, with potential implications for perioperative settings and other anti-PD-1 or anti-PD-L1 therapies.

The REZILIENT1 study investigates zipalertinib, a targeted EGFR exon 20 insertion TKI, in a phase one trial. Previous data showed a 40% response rate after chemotherapy, and new results now focus on patients previously treated with amivantamab. Among these patients, the ORR to zipalertinib remains 40%, and for those who had only received amivantamab (with no prior TKIs or targeted therapies), the ORR increases to 50%. Importantly, the toxicity profile is manageable. These findings suggest that zipalertinib may offer a promising strategy for sequencing targeted therapies in EGFR exon 20 insertion patients, who previously had limited options beyond chemotherapy.

ABBV-400 is an ADC targeting c-Met, combining the monoclonal antibody telisotuzumab with a novel topoisomerase 1 inhibitor. Initially tested in a dose-escalation study, the current dose-expansion trial focuses on patients with non-squamous EGFR wild-type NSCLC. While initially limited to patients with c-Met overexpression (about 25% of cases), the trial was expanded to all patients after responses were observed regardless of c-Met expression levels. The ORR was 48%, with nearly 80% in high c-Met expressors, though this subgroup was small. Despite promising efficacy, ABBV-400 is associated with significant toxicities, including pneumonitis, with one fatal case. This underscores the need for a biomarker to predict responses more accurately. If proven effective across c-Met expression levels, ABBV-400 could have broad clinical applications in the future.