BioNTech sets survival standard in hard

BioNTech has linked gotistobart to median overall survival (OS) of 18.5 months in relapsed lung cancer patients, adding to evidence that the anti-CTLA-4 antibody is better than the standard of care. The data come from Preserve-003, a two-stage phase 3 trial comparing gotistobart to docetaxel in metastatic squamous non-small cell lung cancer (sqNSCLC) patients without actionable genomic alterations. Checkpoint inhibitors work in the first-line population, but the chemotherapy docetaxel, with or without the VEGFR2 antibody ramucirumab, is still the standard of care for patients who relapse. BioNTech used the World Conference on Lung Cancer in Seoul to share updated data from the trial, revealing that the median OS on gotistobart in the first stage of the trial was 18.5 months. Median OS on docetaxel was 10 months, as reported previously. The results confirm the survival advantage that gotistobart appeared to hold over docetaxel at the prior analysis, when OS data on the CTLA-4 antibody were immature. If replicated in the second stage of the trial, the OS result could establish gotistobart as the first breakthrough in the indication in years. BioNTech's co-founder and outgoing chief medical officer Özlem Türeci, M.D., said the data “underscore gotistobart’s potential to redefine treatment for patients with hard-to-treat squamous NSCLC whose disease has progressed after initial therapy and who face limited options.” “In second- and later lines of treatment, the clinical relevance of novel therapeutic options depends on the ability to re-engage a suppressed or exhausted anti-tumor immune response and overcome acquired resistance,” Türeci added in a Monday release. “This update highlights gotistobart’s unique mode of action and our ambition to translate our deep understanding of the immune system into meaningful survival benefit for patients with lung cancer—particularly in areas where patients still need more.” Multiple drugmakers have failed to improve on docetaxel in the population. Gilead’s Trodelvy achieved an OS of 11.1 months, while AstraZeneca and Daiichi Sankyo linked a rival antibody-drug conjugate, Datroway, to an OS of 12.9 months. The combination of Exelixis’ Cabometyx and Roche’s Tecentriq also fell short, delivering an OS of 10.7 months. Median OS on docetaxel in the three trials was 10 to 12 months. Gotistobart’s seemingly superior efficacy comes with safety and tolerability challenges. BioNTech saw serious treatment-related adverse events in 44.4% of patients taking gotistobart, compared to 29.3% for docetaxel. Treatment-related adverse events led 15.6% of people on gotistobart to discontinue therapy, versus 4.9% for docetaxel. Colitis was the most common grade 3 or worse adverse event on gotistobart. Safety and tolerability are long-standing challenges for CTLA-4 antibodies, an immuno-oncology class led by Bristol Myers Squibb’s Yervoy. While gotistobart has inherited some of the issues, the efficacy results suggest work to achieve differentiated outcomes has paid off. The pH-sensitive mechanism is designed to boost depletion of regulatory T cells in the tumor microenvironment, increasing anticancer activity. BioNTech is closing in on data that could confirm that gotistobart has a future in second-line sqNSCLC. On an earnings call last month, Türeci, M.D., said she expected to conduct the first interim analysis from the pivotal stage of the trial toward the end of this year.