A phase II trial of prostate-specific membrane antigen antibody drug conjugate (PSMA ADC) in taxane-refractory metastatic castration-resistant prostate cancer (mCRPC).
2014 Genitourinary Cancers Symposium
J Clin Oncol 32, 2014 (suppl 4; abstr 83)
Author(s): Daniel Peter Petrylak, David C. Smith, Leonard Joseph Appleman, Mark T. Fleming, Arif Hussain, Robert Dreicer, A. Oliver Sartor, Neal D. Shore, Nicholas J. Vogelzang, Hagop Youssoufian, William C. Olson, Nancy Stambler, Kathleen Huang, Robert Joseph Israel; Yale University Medical Center, New Haven, CT; University of Michigan Comprehensive Cancer Center, Ann Arbor, MI; University of Pittsburgh, Pittsburgh, PA; US Oncology Research, The Woodlands, TX; Virginia Oncology Associates, Hampton, VA; University of Maryland Cancer Center, Baltimore, MD; Cleveland Clinic, Cleveland, OH; Tulane Cancer Center, New Orleans, LA; Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC; Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Progenics Pharmaceuticals, Inc., Tarrytown, NY
Background: The abundant expression of prostate-specific membrane antigen (PSMA) on prostate cancer cells provides a rationale for antibody therapy. PSMA antibody drug conjugate (ADC) is a fully human antibody to PSMA linked to the microtubule disrupting agent monomethyl auristatin E (MMAE). It binds PSMA and is internalized and cleaved by lysosomal enzymes releasing free MMAE causing cell cycle arrest and apoptosis. We enrolled 70 patients (pts) in a phase II trial of PSMA ADC in taxane-refractory metastatic castration-resistant prostate cancer (mCRPC). Methods: Pts with progressive mCRPC following taxane and ECOG PS 0 or 1 were eligible. PSMA ADC was administered Q3 week IV for up to eight cycles....1/2
This is the same abstract that caused a sell-off bcz most ppl do not know how to read a scientific paper or evaluate data. Basically... These patients have progressive prostate cancer and it has metastasized to other tissues. They have tried androgen blockade (aka castration resistant prostate cancer and it failed ) and they tried other chemo. Usually they follow PSA and imaging and biopsy but they have noted CTC to be useful. These Circulating cancer cells also have PSMA. The antibodies have a drug hitched to their backside. The antibody binds the PSMA sites on prostate cancer cells and circulating cancer cells. Those that have the most expression of PSMA signals show the best response in decrease in PSA and CTC which one should think would equal death of cancer cells and hence should equate to smaller tumor and better survival. This is what I believe they will share with us tmrw night. So ppl saw price drop or heard results were bad but didn't actually read anything on their own. This hopefully is a learning lesson. Let's hope that in this cancer population that drop in CTC and PSA does mean better survival and smaller tumor. Good luck
In addition, very few are paying attention to phase 2 of the diagnostic - Technetium (Tc99m) trofolastat
"Results: 84 pts were enrolled to date from 16 centers. Interim data is available for 54 pts. A majority (≥2/3) of SPECT/CT readers correctly identified the presence or absence of primary PCa in 51/54 (94%, 85-98 95% CI) patients including 2 true-negative cases treated with neoadjuvant enzalutamide. Sensitivity and specificity were 94% (84-98 95% CI) and 100% (34-100 95% CI) respectively."
"Conclusions: Based on the interim data available, trofolastat has accurately detected primary prostate carcinoma within the gland with high sensitivity and specificity in high-risk pts prior to surgery. Updated results, analyses of secondary endpoints, pelvic lymph nodes, and comparative performance vs. MRI from this ongoing study will be presented. Clinical trial information: NCT01667536."
Safety, tumor response by prostate-specific antigen (PSA), circulating tumor cells (CTC), imaging, biomarkers and clinical progression were assessed. Dosing was initiated at 2.5 mg/kg and adjustment for tolerability was allowed. Results: Thirty five pts began treatment at 2.5 mg/kg. Due to neutropenia, the remaining 35 pts began at 2.3 mg/kg. All pts received prior docetaxel and abiraterone and/or enzalutamide. Forty one percent also received cabazitaxel. Adverse events (AEs) were consistent with what was seen in phase I; most common significant AEs were neutropenia (grade 4, 6.7% and 11.4% at 2.3 and 2.5 mg/kg, respectively) and peripheral neuropathy (grade 3 or higher, 6.7% (2.3) and 5.7% (2.5)). Two pts at 2.5 mg/kg died of sepsis. 43% of pts at 2.3 and 37% of pts at 2.5 had declines in CTC from 5 or more to less than 5 cells/7.5 ml blood and 57.1% (2.3) and 74.1% (2.5) had 50% or more CTC declines; 26.1% (2.3) and 16.1% (2.5) had PSA declines of 30% or more thus far. PSA and CTC responses were associated with higher PSMA expression on CTC and lower neuroendocrine (NE) markers. The CTC conversion rate (5 or more to less than 5) was approximately 80% in pts with low NE markers. Prior cabazitaxel or abiraterone and/or enzalutamide did not appear to affect response. Centralized assessments of images by RECIST of all pts are currently planned and will be presented. Conclusions: PSMA ADC at 2.3 mg/kg was generally well tolerated in pts with progressive mCRPC previously treated with taxane. Anti-tumor activity, CTC and PSA reductions were observed at 2.3 and 2.5 mg/kg. Updated safety, tumor response and radiographic assessments from the full cohorts of 2.3 and 2.5 mg/kg will be presented. Testing in taxane naïve pts is also ongoing. Clinical trial information: NCT01695044.....2/2.