Transcript: WCLC 2026: SCLC expert interview
Supported by Amgen
Giannis Mountzios, MD, PhD
All transcripts are created from interview footage and directly reflect the content of the interview at the time. The content is that of the speaker and is not adjusted by Medthority.
So, this has been an incredible World Conference in Lung Cancer and especially in terms of scientific advances in small-cell lung cancer. We have seen a number of pivotal clinical trials that are expected to change the small-cell lung cancer algorithm pretty sure, and I think that we were all looking forward to those data because they're immediately practice changing, and I will be happy to provide you with more details regarding specific trials. So, in my opinion, MAVERICK was one of the most important trials that was presented to this meeting – very much awaited. As you know, for many years, we thoracic oncologists, we faced a dilemma on whether to provide prophylactic cranial irradiation or not for our patients with limited-stage small-cell lung cancer and especially for patients with extensive-stage small-cell lung cancer where the data have been less robust. So, for years we have been administering prophylactic cranial irradiation in hopes that we don't only delay the intracranial progression that we know is characteristic of small-cell lung cancer but we can also hopefully mitigate some of these brain disease and hopefully increase the survival of our patients. So, MAVERICK is a study that provides a clear answer to this question. It is a prospective randomized clinical trial evaluating the addition of MRI scan that was not integrated in the design of previous clinical trials for small-cell lung cancer.
So, the data we had so far were in the pre-MRI era, but now we have the option of including an MRI of the brain every 3 months for the first period of observation and after that every 6 months, as it was in the trial. And what we saw actually in the MAVERICK trial is that the MRI surveillance strategy was first of all non-inferior to the prophylactic cranial irradiation plus MRI surveillance strategy, both in terms that it substantially improved the cognitive failure-free survival of the patients, and that is very important for the quality of life of the patients because we are all aware of the important side effects that prophylactic cranial irradiation carries for cognitive and also psychological effects on the patients. And second, MAVERICK provided, for the first time, data that although intracranial progression- free survival was improved in the prophylactic cranial irradiation arm, on the other hand, we saw that with MRI surveillance we had non-inferiority, meaning that overall survival was not impacted, was not inferior in the MRI surveillance arm. And this, in my opinion, as was also discussed in the trial is largely due to the fact that we now have novel stereotactic radio surgery techniques. With those new techniques we can manage those new brain metastases in an effective way that we did not have in the past. And this can significantly prolong patient survival and lead to [broadly similar] outcomes with MRI surveillance.
So, collectively those data suggest that the strategy of active brain MRI surveillance is non-inferior to prophylactic cranial irradiation, meaning that we can skip prophylactic cranial irradiation for our patients with limited-stage disease and especially for patients with extensive- stage small-cell lung cancer because, even at the first occurrence of brain metastasis, we have effective treatment options, radiotherapy techniques, sophisticated, that can lead to [similar] survival outcomes for those patients. So, those two studies presented at the presidential symposium, one were two very significant studies as well in this congress because, for the first time, we saw clear randomized phase 3 data of antibody–drug conjugate efficacy in pre-treated patients with extensive-stage small-cell lung cancer. So, we had two antibody–drug conjugates: Tam-Peli in the one trial and in the other trial is risvutatug rezetecan, or Ris-Rez, two ADCs that are both targeting B7-H3 and have a TOPO-1 payload. And both trials showed a significant overall survival benefit compared to second-line topotecan in patients with extensive-stage small-cell lung cancer prior treated with platinum-based chemotherapy plus an immune checkpoint inhibitor.
This is really, those two are game-changing trials because they introduce ADCs in the second-line treatment of small-cell lung cancer. We are expecting more phase 3 trials with other antibody–drug conjugates in the same setting to read out very soon, also incorporating different targets, such as DLL3 and SEZ6. So, this is becoming a really competitive landscape in the second-line setting and, of course, this is great news for our patients since we have now, as oncologists, we are going to have much more options to treat our patients and especially in the second-line setting that was a setting where we had really limited options in the past. So, as you know, many, many of the trials presented in this congress as well are evaluating the contribution of T-cell engagers, and we know that T-cell engagers have transformed the therapeutic field, landscape, of small-cell lung cancer with the approval of the first T- cell engager in class, tarlatamab, by the FDA back in 2024 and by the EMA recently just in June 2026. So, now we have a new standard of care in the second- line setting, which is tarlatamab, and we saw in this congress a number of trials. First of all, we had a trial evaluating different dose regimens of tarlatamab in the second-line setting. So, we saw that the regimens of 10 mg every 2 weeks, 20 mg every 3 weeks, and 30 mg every 4 weeks are [similar] in terms of efficacy and also in terms of safety. And this provides more comfort to our patients because we have now the options to deliver tarlatamab in different time intervals according to the patient comfort. Also, we saw for the first time phase 1 data for the subcutaneous administration of tarlatamab.
So, for the first time we had a T-cell engager that can be administered subcutaneously and we saw that this does not compromise efficacy of the component. So tarlatamab at the dose of 15 mg subcutaneously is [similar] to the dose of 10 mg in terms of efficacy and, on the other hand, it can help mitigate important side effects of tarlatamab, such as CRS. So, subcutaneous administration is associated with less CRS incidence for our patients. And, of course, we saw data on other T-cell engagers as well that are coming into the field as monotherapy and also as combinations with immune checkpoint inhibitors and antibody–drug conjugates. Moving to the first line, we saw a number of posters with phase 1b trials evaluating combinations of T-cell engagers plus antibody–drug conjugates with or without immune checkpoint inhibitors in several cohorts of patients in the first-line setting. So, I believe we have made substantial progress so far, but there are a lot of things that remain to be done. We need to improve the outcomes for our patients in the second-line setting with the advent of ADCs. We have a lot of hopes there, and another fascinating aspect is that T-cell engagers are starting moving to the first-line setting. So, the next step, the next frontier for small- cell lung cancer is to see how we can optimally combine T-cell engagers and antibody–drug conjugates as well as platinum-based chemotherapy and immune checkpoint inhibitors in the first-line setting, to which patients and with what sequence, and also the duration of treatment with agents as ADCs will be critical to define the optimal management of patients in the first-line setting.
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