ESMO 2025 | Novel bispecific antibodies, BITESs and ADCs for neuroendocrine carcinomas

As with all other solid tumors at the moment, there are investigations going on and there are novel agents being developed, specifically bispecific antibodies, bispecific T-cell engagers, and antibody drug conjugates. And there was some evidence presented at meetings earlier in the year of different bispecific antibodies and antibody drug conjugates. And they are tending to show that they potentially have a better response rate. We know the response rate in the first line setting is around 50%. In the second line setting is around 18%. And in these trials, they have shown one of the first-line trials showed a response rate with an antibody drug conjugate, which was around over 70%, which is potentially promising. There have been bispecific T-cell engagers, and there was a phase one study which has been reported of a compound called a obrixtamig . And that has been looked at in patients with small cell lung cancer, large cell neuroendocrine carcinoma of the lung, and extrapulmonary neuroendocrine carcinoma. And this agent, there was over 160 patients included in that trial. And they found a response rate for the extrapulmonary neuroendocrine carcinoma of 27%. And these are patients who had at least over 70% had greater than two lines of previous therapy. So a response rate of 27% is good in that setting. And they looked specifically at the patients with poorly differentiated neuroendocrine carcinoma to see was there any marker or biomarker they could see which might predict patients who would do better. And they saw that patients who had a DLL3 high expression in their tumors had a response rate of 40% versus 3% with the patients whose tumors were DLL3 low. So this is potentially a promising agent. And there are ongoing clinical trials listed on clinicaltrials.gov in the first line and beyond first line setting. And the first line trial is immunotherapy combination with platinum etoposide versus platinum etoposide alone that’s running in the US and then there are other trials beyond first line so in the relapsed or refractory setting and they are they are investigating as I said the antibody drug conjugates and the bispecific antibodies bispecific T cell engagers and they are running in Asia and in the US and the primary endpoint in those trials is response rate. So hopefully in the future there will be additional options for these patients and we will await the outcomes of these studies and hope that it will improve outcomes for these patients.

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