Two Experimental ADCs Significantly Extend Survival in Relapsed Small-Cell Lung Cancer

Two Chinese trials found that the anti-B7-H3 antibody-drug conjugates tambotatug pelitecan and risvutatug rezetecan each reduced the risk of death by 54% compared with standard chemotherapy in relapsed small-cell lung cancer. Both drugs also improved progression-free survival and objective response rates substantially. The results were presented at the World Conference on Lung Cancer and published in the New England Journal of Medicine.

Both phase III trials enrolled patients with relapsed disease, most of whom had already received checkpoint inhibitor therapy, and roughly half carried platinum-resistant tumors. About one-third of participants had brain metastases at baseline, a group often underrepresented in lung cancer studies. Notably, severe adverse events occurred less frequently with the experimental agents than with topotecan, suggesting a more manageable toxicity profile.

The FDA has already granted priority review to a third B7-H3-directed ADC, ifinatamab deruxtecan, for extensive-stage SCLC, with a decision expected in October. The conference discussant predicted that ADCs could become the standard second-line treatment within two to five years and may eventually move into front-line use, potentially displacing chemotherapy altogether.