This was another secondary outcome of the DeLLphi-304 trial. Importantly, patients that were included in this study and were randomised either to tarlatamab or to standard second-line chemotherapy were stratified by whether the patients had been previously exposed to an immune checkpoint inhibitor or not as part of their first-line treatment. Second, patients were stratified according to the chemotherapy-free interval, which is the interval in days lagging between the last dose of platinum-based chemotherapy and the date of confirmed disease progression. The stratification in that aspect was less than 90 days, 3 months, between 90-180 days, so between 3-6 months, and more than 180 days which was more than 6 months. Simply speaking, the trial stratified patients according to prior platinum sensitivity: less than 3 months was considered platinum resistance; between 3-6 months was considered potentially platinum sensitive and more than 6 months was considered platinum sensitive disease.

What were the key findings?

Importantly, the trial showed two very important things. The first one is that the benefit in terms of overall survival that we see with tarlatamab over second-line chemotherapy persisted and was similar, independent of prior immune checkpoint inhibition or not. That means that patients who had received chemotherapy plus an immune checkpoint inhibitor as first-line treatment derived similar benefit from tarlatamab as compared to patients who received only chemotherapy as first-line treatment.

This notion is important because we know that immune checkpoint inhibitors are also a kind of immunotherapy, similar to T-cell engagers; they both belong to the wide spectrum of immunotherapy. So I believe it is reassuring to know that the prior use of immune checkpoint inhibitor did not affect the benefit from tarlatamab.

Regarding the second endpoint, which was chemotherapy-free interval, again the trial showed very consistent results that the benefit of tarlatamab was similar independently of the chemotherapy-free interval and, importantly, was even better. The hazard ratio was less than 0.5 for patients whose disease had progressed less than 90 days after last dose of platinum-based chemotherapy which are the chemo-resistant patients. So those patients had important clinical benefit from tarlatamab as well.

What is the clinical significance of these results?

In my opinion this sub-study provides answers to two very critical questions for medical oncologists in clinical practice. The first one – prior use of immune checkpoint inhibitor does not affect the efficacy of tarlatamab in the second-line setting. We know today that at least 70% of our patients get an immune checkpoint inhibitor together with chemotherapy in the first-line setting.

Second, and even more important, the chemotherapy-free interval does not impact efficacy of tarlatamab in clinical practice and especially for patients who are considered chemo-resistant and who have no valid alternative options, second-line treatment with tarlatamab is an excellent option for all patients but especially for patients with chemo-resistant disease who represent a highly unmet medical need.