Early Results With PSMA-Targeting T-Cell Engager in Metastatic Prostate Cancer
Posted: Wednesday, July 7, 2021
Johann S. De Bono, MD, PhD, of The Institute of Cancer Research and Royal Marsden Hospital, London, and colleagues conducted a phase I/IIa dose-escalation study of HPN424—a trispecific, half-life extended, prostate-specific membrane antigen (PSMA)-targeting T-cell engager—in patients with metastatic castration-resistant prostate cancer. During the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, these researchers announced that this novel immunotherapy was not only well tolerated with manageable adverse events, but there was also evidence of antitumor activity (Abstract 5013).
The investigators focused on 80 patients with metastatic castration-resistant prostate cancer who underwent more than two previous systemic therapies. Participants were administered HPN424 once weekly in target doses ranging from 1.3 to 160 ng/kg, up to 300 ng/kg with step dosing.
The median number of previous systemic therapies was six, with 75% of patients having received prior chemotherapy. Grade 3 treatment-emergent adverse events such as an increase in aspartate transaminase (18%) and alanine transaminase (11%) and anemia (11%) were among the most common; transaminase increases were noted to be temporary. Additionally, grade 3 cytokine-release syndrome (n = 3), seizures (n = 1), and elevated lipase (n = 1) presented as dose-limiting toxicities, although the maximum tolerated dose has not been achieved.
Among the 63 patients who had post-baseline levels of prostate-specific antigen (PSA), 13 (21%) experienced a decline from baseline. PSA level declines were also observed in five chemotherapy-naive patients, as well as three of seven patients who achieved the highest fixed dose of 160 ng/kg; one individual reached a confirmed partial response. Of note, a reduction in circulating tumor cells was observed in 57% of participants who had measurable levels at baseline.
Of 62 patients with more than 24 weeks of follow-up, nearly one-quarter (24%) remained on treatment for at least 24 weeks. The primary reason for treatment discontinuation was disease progression, but two patients halted therapy due to adverse events.
Disclosure: For full disclosures of the study authors, visit coi.asco.org.