ESMO 2025 | OptiTROP-Lung04: sacituzumab tirumotecan in EGFR-mutated NSCLC

So, the management of patients with EGFR mutant non-small cell lung cancer that progress to the first-line setting with TKI alone, generally osimertinib worldwide, is very difficult because the rest of the patients are heterogeneous and polyclonal. At the present time, we know that the target single alteration, like MET, is effective but is not so easy to extend to a wide patient population. And in this particular field, we have already approved in the last two years different biomarker-agnostic strategies. The first is the combination of chemotherapy plus amivantamab, the MAIRPOSA study. The second is the combination chemotherapy plus ivonescimab for the HARMONi trial that is approved exclusively in China. During the ESMO 2022, we presented very interesting data, the OptiTROP-Lung04 trial. This is the first phase three trial that reported data with an ADC in patients with EGFR alteration in the first trial with positive results. Indeed, the authors reported that patients randomized to receive a platinum chemotherapy or OptiTROP-Lung04: sacituzumab tirumotecan in EGFR-mutated NSCLC and the results showed very impressive results in favor of all the efficacy endpoints. So we have an improving progression-free survival, an improving overall survival, an improved overall response rate for patients that were randomized to receive OptiTROP-Lung04: sacituzumab tirumotecan in EGFR-mutated NSCLC. In general, globally, toxicity was good, more or less manageable, and with less grade 3 than the standard chemotherapy. And the only one toxicity with some concern is stomatitis. That is one of the characterizing toxicities for ADC in this kind of setting. Globally, I think that this is a very clear and positive study developed exclusively in China. And now it’s important to understand also the regulatory approval to consider if this kind of drug could be applied and approved in Europe and the FDA based on this trial. But it’s important to know that at the present time there is an ongoing trial, DESTINY-LUNG01, that is the global trial with the same study impairment in patients progressing after EGFR-tyrosine kinase inhibitors. Interestingly, in this field, we have many, many ADCs in evaluation. The others are that of the Rocaftengan, ongoing in a phase 3 trial, the Tropion Lung 15, and then we have also Isapretin, a B-specific ADC against HER3 and EGFR, and Temozolomide BA, a very interesting ADC targeting c-MET, in an important way and pathway for this kind of patient. Globally, we can consider that in the last two years, with the improvement in the first-line setting with the combo FLAURA2 and MARIPOSA, and the improvement in second-line SACITUZUMAB, MARIPOSA 2, HARMONY, also Optitrop Lung 04. The treatment scenario for patients with EGFR alteration is improving step by step hoping for a better survival for our patients.

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