Pfizer has terminated its Phase I PF-08046031 clinical trial in adults with advanced melanoma and other solid tumors, according to an update on ClinicalTrials.gov (NCT06799533). The decision ends clinical development of the company’s sole CD228-directed antibody-drug conjugate, a molecule inherited through its USD 43 billion acquisition of Seagen in 2023. Only 11 participants were enrolled before the study was stopped, and no results have been posted to the registry. The clinicaltrials.gov listing indicates the decision was taken for strategic reasons with no safety or efficacy concerns.
PF-08046031, formerly designated SGN-CD228A under Seagen’s pipeline, is a humanized IgG1 monoclonal antibody conjugated to approximately four molecules of monomethyl auristatin E (MMAE) via a cleavable vedotin-type linker. The ADC was designed to bind CD228 — also known as melanotransferrin — on the surface of tumor cells, internalize, and release its cytotoxic payload within the lysosome, disrupting microtubule polymerization and triggering G2/M cell cycle arrest. CD228 is expressed at elevated levels in melanoma, non-small cell lung cancer (NSCLC), head and neck squamous cell carcinoma (HNSCC), and esophageal cancer, with limited expression in normal tissues.
The study was an open-label, single-arm, sequential assignment trial designed to assess dosing levels in patients with metastatic or unresectable cutaneous melanoma previously treated with an anti-PD-1/PD-L1 regimen. The trial included dose-escalation and dose-optimization cohorts in melanoma, with a planned expansion to also include patients with non-small cell lung cancer, head and neck squamous cell carcinoma, and esophageal cancer.