Ricardo - PSMA ADC Study for Metastatic Castration-resistant Prostate Cancer (mCRPC)
Progenics licenses SGEN ADC technology (ADCETRIS) in its phase 2 PSMA ADC Study for Metastatic Castration-resistant Prostate Cancer (mCRPC). The top-line result is scheduled to release at the 2014 ASCO in January. However, there are some AE's related to the drug being used in the trial that including 2 drug related deaths.
PSMA ADC. We are conducting a phase 2 trial of PSMA ADC to assess its anti-tumor activity and tolerability. In this open-label, multicenter U.S. study, participants with metastatic castration-resistant prostate cancer (mCRPC) have received initial doses of drug starting at either 2.5 mg/kg or 2.3 mg/kg; in some cases subsequent doses were adjusted based on tolerability. The study endpoints evaluate the anti-tumor effect of the compound as measured by changes in prostate specific antigen (PSA) levels, number of circulating tumor cells (CTC), pain scores, and tumor size as measured under RECIST criteria. Safety is also being assessed. Progenics announced in December 2013 that it has completed enrollment of 83 chemotherapy experienced patients in this trial and has initiated treatment in an additional trial cohort of up to 35 chemotherapy naive patients who have progressed on hormonal therapies.
Adverse events (AEs) associated with PSMA ADC observed in this phase 2 study through mid-2013 have been consistent with those observed in the phase 1 study noted below; the most common grade 3 or higher AEs in this study have been neutropenia (grade 4: 6.7% at 2.3 mg/kg and 11.4% at 2.5 mg/kg) and peripheral neuropathy (grade 3 or higher: 6.7% at 2.3 mg/kg and 5.7% at 2.5 mg/kg).
Eight patients experienced serious adverse events (SAEs) which included febrile neutropenia, neutropenia, sinus tachycardia, gastrointestinal disorders, fatigue, infections and dehydration. Two deaths occurred after treatment with PSMA ADC. The first, a patient hospitalized ten days following his first dose of study drug (2.5 mg/kg) with febrile neutropenia and E. coli positive blood cultures, progressed despite treatment to septic shock and died; both the investigator and Progenics considered this patient's septic shock as probably related to PSMA ADC. The second patient developed a rash and fever and was hospitalized for neutropenic fever, where further assessment revealed Strep Viridans bacteria (suspected to be from a tunnel catheter) in blood. Approximately two weeks after receiving study drug (also 2.5 mg/kg), this patient was intubated due to hypoxia and respiratory failure, and died three days after being removed from a ventilator. The investigator considered sepsis as unlikely, bacteremia as probably, febrile neutropenia as definitely related to PSMA ADC; Progenics assessed sepsis as probably, bacteremia as unlikely, and febrile neutropenia as definitely related to PSMA ADC. A third patient died before receiving study drug.
The phase 2 trial was undertaken after review and analysis of results from a phase 1 dose-ranging study of the compound in 52 mCRPC patients whose cancer had progressed despite prior treatment with taxane-based chemotherapy regimens.