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ESMO 2017

ESMO 2017: Phase I study of the PSMA-targeted small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer

Madrid, Spain (UroToday.com) Dr. Morris and colleagues presented their phase I results of utilizing the PSMA-targeted small-molecule drug conjugate EC1169 for patients with metastatic castration-resistant prostate cancer (mCRPC). As we have seen over the past several years, prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer tissue, but not in most non-prostate normal tissues, thus making it a potential therapeutic target. EC1169 is a PSMA-targeted conjugate of the microtubule inhibitor tubulysin B hydrazide and is being studied in a two-part phase 
I dose escalation/expansion study in mCRPC, which has been completed. The objective of the current study is to assess the utility of the PSMA-targeted companion imaging agent 99mTc-EC0652 as a patient selection tool in the second part of this protocol. 

For this study, 34 of a planned 85 patients received EC1169 administered as an IV bolus on days 1 and 8 every 21 days. The dose of 6.5 mg/m2 was determined in the initial part of the study, leaving the 85 patients in the current portion of the study to be treated with the same dose, stratified by: (i) mCRPC taxane naïve (cohort 1, n=45) or taxane exposed (cohort 2, n=40). Prior to treatment, patients undergo a 99mTc-EC0652 SPECT/CT scan. The primary endpoint of this study is median radiographic progression-free survival (rPFS). Secondary outcomes include overall survival, PSA response, and CTC-based biomarkers. Among the 34 treated patients, 14 are taxane naïve and 20 are taxane exposed. The median age of these patients is 70 (range: 49-84) and median number of cycles is 3 (range: 1-7). Six of twelve evaluable taxane-exposed patients had stable disease or better at their first post-baseline scan (9 weeks), and one patient currently beyond the 18-week scan has achieved durable resolution of his soft tissue disease. Imaging with 99mTc-EC0652 suggests excellent disease localization. Overall, there were 26 patients (76.5%) who reported at least one treatment related adverse event, most of which were Grade 1 and 2 treatment related events.

The authors concluded that the dose of EC1169 6.5 mg/m2 is well tolerated among the first 34 patients treated. This PSMA-targeted therapeutic strategy appears viable, with evidence of anti-tumor activity in both the taxane naïve and taxane exposed patients. 

Speaker: Michael Morris, Memorial Sloan Kettering Cancer Center, New York, United States of America

Co-Authors: N. J. Vogelzang (Las Vegas, United States of America) O. Sartor (New Orleans, United States of America) A. Armour (Indianapolis, United States of America) M. Groaning (Indianapolis, United States of America) R. Messmann (West Lafayette, United States of America) A. Robarts (New York, United States of America) D. P. Petrylak (New Haven, United States of America) A. Tolcher (San Antonio, United States of America) M. S. Gordon (Scottsdale, United States of America) H. Babiker (Tucson, United States of America)

Written By: Zachary Klaassen, MD, Urologic Oncology Fellow, University of Toronto, Princess Margaret Cancer Centre, Twitter: @zklaassen_md at the European Society for Medical Oncology Annual Congress - September 8 - 12, 2017 - Madrid, Spain