Mini oral session 1

In this video, Prof Dr Lore Decoster provides a brief summary of the first mini-oral session of the 2025 European Lung Cancer Conference (ELCC).

The first 2 abstracts in the session zoomed in on patients with non-oncogene driven advanced non-small-cell lung cancer (NSCLC). The phase II MK-3475A-D77 study compared the pharmacokinetics, safety and efficacy of a subcutaneous (SC) formulation of pembrolizumab to the classic intravenous (IV) formulation. The SC formulation consists of an injection of 4.8 mL, which could be administered with a median injection time of 2 minutes every 6 weeks. As such, this SC formulation comes with a markedly lower treatment burden than the IV formulation. Pembrolizumab SC proved to be non-inferior to the IV formulation in terms of steady-state trough concentration, safety and efficacy. Once available, this SC formulation will therefore become the new standard of care.¹

Also in non-oncogene driven advanced NSCLC, a phase II study compared the PD-1 and LAG-3 directed bispecific antibody tobemstomig to pembrolizumab, both in combination with platinum-based chemotherapy. Unfortunately, the study failed to show an advantage with the addition of LAG-3 inhibition in this setting. As a result, the development of this agent in NSCLC has been stopped.²

Mini oral session 1 also featured 3 studies in patients with KRAS-mutant advanced NSLCL. In the phase II KRYSTAL-7 study, first line adagrasib in combination with pembrolizumab was associated with an objective response rate (ORR) and disease control rate (DCR) of 59% and 81%, respectively, in patients with KRASG12C-mutant, advanced NSCLC with a PD-L1 expression ≥50%.³ The phase III KRYSTAL-4 study will now try to confirm these findings in a randomized setting.

Also in advanced KRASG12C-mutant NSCLC, the phase II KROCUS study showed that first line therapy with a combination of fulzerasib and cetuximab resulted in an ORR of 80% and a DCR of 100%. While these findings are very promising, especially given the fact that this concerns a chemotherapy-free regimen, we need to await their validation in a randomzied phase III trial.⁴

A final study in KRAS-mutant advanced NSCLC evaluated the pan-RAS inhibitor daraxonrasib. Interestingly, this agent is not only directed against mutations in KRAS, but also targets NRAS and HRAS, meaning that this treatment could potentially be used in a large proportion of NSCLC patients. In the presented, first-in-human study, this agent proved to be associated with a confirmed ORR of 38% in previously-treated, RAS-mutant advanced NSCLC patients (exlcuding KRASG12C-mutant patients). The treatment was generally well tolerated, with most adverse events being gastrointestinal in nature. A phase III study with this agent (RASolve 301) in previousl-treated, RAS-mutant advanced NSCLC is currently ongoing.⁵

A final abstract of the mini oral session that was addressed by Prof Decoster featured the results of the COCOON trial. This phase II study evaluated an elaborate dermatological prevention regimen in EGFR-mutant, advanced NSCLC patients receiving a combination of lazertinib-amivantamab. Given the overall survival benefit that was demonstarted with this combination over osimertinib in the MARIPOSA trial, this regimen will increasingly be used in the near future. However, this treatment comes with a substantial toxicity burden, including a high incidene of dermatologic adverse events. In COCOON, dermatological prevention with oral doxycycline/minocycline (100 mg BID, weeks 1–12), clindamycin 1% lotion on scalp (QD, weeks 13–52), chlorhexidine 4% to wash hands & feet QD, & non-comedogenic ceramide-based moisturizer to body & face QD reslted in a 50% lower incidence of grade ≥2 dermatological adverse events. Importantly, however, despite this regimen, 40% of patients still experienced grade ≥2 adverse events.⁶ For Dr Decoster, adherence to preventive strategies, such as the one used in COCOON, will be very important to maximize the potential benefit of lazertinib-amivantamab in patients with EGFR-mutant NSCLC