Progenics Pharmaceuticals, Inc. today reported positive preliminary data from an ongoing phase 1 study of PSMA ADC, an antibody-drug conjugate (ADC) designed to selectively deliver chemotherapy to cells that express prostate-specific membrane antigen (PSMA). Antitumor activity, as reflected by clinical and/or laboratory measures, was observed in four of nine patients treated at the highest tested dose of 1.8 mg/kg. PSMA ADC was generally well tolerated in patients treated to date, and patient enrollment continues at a higher dose. Findings were presented at the 2011 Genitourinary Cancers Symposium, a meeting co-sponsored by the American Society of Clinical Oncology (ASCO), the American Society for Radiation Oncology (ASTRO) and the Society of Urologic Oncology (SUO).
Data were reported for 21 patients who have been administered PSMA ADC at five dose levels between 0.4 mg/kg and 1.8 mg/kg. Of the nine patients treated at 1.8 mg/kg, four (44%) exhibited a decline in PSA (prostate-specific antigen), CTC (circulating tumor cells) and/or bone pain. In addition, one patient of three (33%) treated at 1.6 mg/kg showed a decline in CTC and bone pain.
The most common clinical adverse event was fatigue, while the most common laboratory adverse events were reversible neutropenia and elevations in liver enzymes. One patient experienced an acute, fatal case of pancreatitis that was deemed by the investigator to be possibly related to treatment. No evidence of pancreatic toxicity has been observed with PSMA ADC in other treated patients, consistent with results of preclinical studies. PSMA ADC exhibited dose-proportional pharmacokinetics, and no antibodies to PSMA ADC were observed in any subject. A maximum tolerated dose has not been determined, and enrollment of patients at a dose of 2.0 mg/kg has commenced.
"Treatment with PSMA ADC in this ongoing study resulted in meaningful reductions in two commonly used biomarkers of prostate cancer progression as well as in cancer-related bone pain, a common complication of prostate cancer," said Robert J. Israel, M.D., Progenics' Senior Vice President, Medical Affairs and Clinical Research. "These findings were observed in patients with tumors that had progressed despite standard chemotherapy. Based on these encouraging data, we look forward to further exploring the potential utility of this novel agent."
A poster, entitled "Prostate-specific membrane antigen antibody drug conjugate (PSMA ADC): A phase 1 trial in taxane-refractory prostate cancer" is being presented today by Daniel P. Petrylak, M.D., professor of Medicine, program director of the Genitourinary Oncology Section in the Division of Hematology/Oncology, and co-leader, Prostate Cancer in the Herbert Irving Comprehensive Cancer Center at Columbia University Medical Center. This poster will be available for the next 30 days on the Events page of Progenics' website.
Phase 1 study design
The phase 1, open-label, dose-escalation clinical trial is being conducted in men with hormone-refractory prostate cancer that has progressed despite prior treatment with taxane-based chemotherapy regimens. In addition to assessing PSMA ADC's safety and tolerability, the study includes evaluations of pharmacodynamics, changes in tumor burden, and changes in PSA and CTC values compared to baseline. PSA is a secreted protein that is unrelated to PSMA.
The initial 12-week clinical trial period evaluates up to four intravenous doses of PSMA ADC administered at three-week intervals. Following completion of the four doses, patients are offered, at their physicians' discretion, the option to continue treatment with PSMA ADC for up to an additional 39 weeks. Qualified individuals receive up to 13 additional doses of study drug at three-week intervals.
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