Novel Therapy Appears Safe in Certain Patients with Prostate Cancer

Treatment with the novel therapy HPN424 induced antitumor activity in patients with metastatic castration-resistant prostate cancer (mCRPC), according to results from an ongoing phase 1/2a study.

The findings, which were presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, also showed that the tri-specific half-life extended prostate-specific membrane antigen (PSMA)-targeting T cell engager was well tolerated among patients.

The phase 1/2a study evaluated the agent in patients with mCRPC who have received more than two prior systemic therapies. The median age was 70 years (range, 43-91) and the median number of prior therapies was five (range, 1-12), with 73% of the men having received prior chemotherapy. Most (78%) of the patients were White, whereas 9% were Black, 2% were Asian, and 11% were classified as other/not reported.

Observing safety, tolerability and identifying a maximum-tolerated dose/recommended phase 2 dose was the main goal of the study. Other goals included, but were not limited to, assessing antitumor activity.

The study comprised a fixed-dose treatment group of 70 patients and a step-dose (or dose escalation) group of 19 patients. As of April 23, 89 patients had received treatment. Maximum targeted doses assessed to date in the step-dose group was 160 mg/kg and 300 mg/kg in the fixed-dose group.

Confirmed partial response to therapy, prostate-specific antigen decline (elevated PSA levels are often, but not always, indicative of presence of prostate cancer), and circulating tumor cell (cancer cells shed from a primary tumor or its metastases that circulate in peripheral blood) reduction occurred in both treatment groups. More than half (57%) of the 56 evaluable patients achieved a reduction in circulating tumor cells.

“Overall, across the entire study, 15 of 74 patients … with at least six months of follow-up have remained on treatment beyond 24 weeks,” study author Johann De Bono, head of drug development at The Institute of Cancer Research in London, United Kingdom, said while presenting the data. “PSA declines from baseline have been observed in 20% of evaluable patients.

Cytokine release syndrome (a rapid release of cytokines into the blood from immune cells affected by treatment) and transaminitis (elevated levels of certain liver enzymes) were the most common treatment-related side effects, and they occurred most often in the first cycle of treatment, according to de Bono. Other cytokine-related side effects included chills, fever, hypotension, infusion-related reaction, flushing and hypoxia (lack of oxygen to the body’s tissues). Other reported side effects included fatigue, nausea, vomiting, anemia, headache, back pain, tachycardia, constipation, and decreased appetite.

“HPN424 has been generally well tolerated,” de Bono concluded. “Two patients discontinued due to treatment-related adverse events. The (maximum-tolerated dose) has not yet been reached for either the step dose or fixed dose arms.”

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