New therapy appears safe in some prostate cancer patients

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

The results, which were presented at the 2021 annual meeting of the American Society of Clinical Oncology (ASCO), also showed that the engagement of T cells targeting prostate-specific membrane antigen (PSMA) at half- tri-specific life was well tolerated in patients.

The phase 1 / 2a study evaluated the agent in patients with mCRPC who received more than two previous systemic treatments. The median age was 70 (range, 43-91) and the median number of previous treatments was five (range, 1-12), with 73% of men having received previous chemotherapy. Most (78%) of the patients were white, while 9% were black, 2% were Asian, and 11% were classified as other / unreported.

Observation of safety, tolerability and identification of a phase 2 maximum tolerated / recommended dose was the primary objective of the study. Other purposes included, but not limited to, evaluation of anti-tumor activity.

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

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

“Overall, across the study as a whole, 15 of 74 patients … with at least six months of follow-up remained on treatment beyond 24 weeks,” study author Johann De Bono, head of drug development at the Institute of Cancer Research in London, UK, said during the data presentation. “Decreases in PSA from baseline were observed in 20% of evaluable patients.

Cytokine release syndrome (rapid release of cytokines into the blood by immune cells affected by treatment) and transaminitis (high levels of certain liver enzymes) were the most common treatment-related side effects, and they occurred on more often during 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 in body tissues). Other side effects reported included fatigue, nausea, vomiting, anemia, headache, back pain, tachycardia, constipation, and decreased appetite.

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

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