SGN-BB228

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. Context from Pfizer’s broader pipeline activity offers one plausible frame. Following the Seagen acquisition, Pfizer undertook a series of portfolio rationalization exercises, discontinuing 11 programs in late 2024, with additional cuts following shortly after. A separate earlier-stage trial of SGN-CD228A (NCT04042480) was also terminated, leaving no active clinical studies for this molecule. According to public data, Pfizer retains an interest in CD228 in the form of PF-08046049 (SGN-BB228), a CD228 x 4-1BB bispecific currently under Phase I study (NCT05571839), also being targeted towards melanoma. For Pfizer’s broader oncology portfolio, the loss is one of several Seagen-inherited assets shed as the company narrows its ADC strategy. Pfizer retains other ADC programs built on the vedotin/MMAE platform, including the marketed products brentuximab vedotin (Adcetris) and enfortumab vedotin (Padcev), as well as tisotumab vedotin (Tivdak). Your email address will not be published. Required fields are marked * Comment * Name * Email * Website