ASCO 2017: Phase 1 study of the PSMA-targeted small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer

Chicago, IL ( Prostate-specific membrane antigen (PSMA), as its name indicates, is a prostate specific antigen that has enabled novel imaging technologies to better detect small volumes of prostate cancer. The PSMA-PET scan, introduced in the past few years, has become increasingly popular at certain centers as a tool to identify small volume disease in evidence of oligometastatic disease.
However, due to its specificity, the interest in utilizing PSMA as a guide for therapeutic purposes has been increasing. As different agents can be tagged to PSMA, the number of therapeutic options increases. In the German experience, 177Lutetium has reportedly had some success.1

In this two-part phase 1 study, the authors investigate the clinical utility of EC1169, a PSMA-targeted conjugate of the microtubule inhibitor tubulysin B hydrazide, in patients with metastatic castration-resistant prostate cancer (mCRPC). In the first part (Part A), they assess safety and efficacy, while Part B is a 2-stage, 2-cohort expansion.

Study Design:
Patients with (mCRPC) who had progressed on abiraterone or enzalutamide who had also been treated with taxane chemotherapy were included in Part A of the study. Part B patients are being enrolled in 2 cohorts, taxane naïve (cohort 1) and taxane-exposed (cohort 2). EC1169 was administered as an IV bolus on days 1 & 8 every 3 weeks. Prior to treatment, patients undergo a 99mTc-EC0652 SPECT scan. Primary clinical outcome was radiographic progression-free survival (rPFS). Secondary objectives were to assess safety, median PFS, median OS, and evaluate blood based markers and imaging biomarkers for efficacy correlation.

Part A has been completed, and the dose escalation assessment identified 6.5 mg/m2 as the best dose with minimal toxicity.

Forty patients have undergone treatment through both parts (16 taxane naïve, 24 taxane exposed). Across the entire cohort, there was an even mix of Gleason 4-7 and Gleason 8-10 patients on initial diagnosis. Baseline PSA median value was 104. 85% had received prior androgen-receptor directed therapy. 60% had received prior chemotherapy. 

Overall, the treatment was well tolerated – only 5% had grade 3/4 drug-related adverse events. No dose reductions were required. Most of the adverse events were grade 1-2 toxicity. 

In terms of clinical response, 6 of 16 taxane-naïve patients had measurable soft tissue disease during follow-up, of which 4 had stabilization of the disease and the other 2 have not reached the first assessment point. In the taxane-exposed group, 13 patients had measurable soft tissue disease. One patient had confirmed partial response, 5 had stabilization of disease, 1 had radiographic progression, and 5 had discontinued treatment. There appears to be evidence of treatment response with tumor shrinkage and stabilization of disease. 

LDH and alkaline phosphate decreases were noted in a large proportion of patients, while PSA has not shown similar responses. 

There appears to be good localization with this conjugate, and early clinical assessment suggests potential clinical response. While longer follow-up is required, this may represent a good treatment option for oligometastatic disease. 

Presented By: Michael J. Morris, MD, Memorial Sloan Kettering Cancer Center and Weil Cornell Medical College, New York, NY

Co-Author(s): Nicholas J. Vogelzang, Oliver Sartor, Alison Armour, Michael Groaning, Adam Robarts, Daniel Peter Petrylak, Anthony W. Tolcher, Michael S. Gordon, Hani M. Babiker

Institution(s): Comprehensive Cancer Centers of Nevada, Las Vegas, NV; Tulane University School of Medicine, New Orleans, LA; Endocyte, Indianapolis, IN; Endocyte, West Lafayette, IN; Memorial Sloan-Kettering Cancer Center, New York, NY; Yale School of Medicine, New Haven, CT; START, San Antonio, TX; Pinnacle Oncology Hematology, A Division of Arizona Center for Cancer Care, HonorHealth Research Institute Clinical Trials Program at the Virginia G. Piper Cancer Center, Scottsdale, AZ; University of Arizona Cancer Center, Tucson, AZ

Written By: Thenappan Chandrasekar, MD, Clinical Fellow, University of Toronto
Twitter: @tchandra_uromd

at the 2017 ASCO Annual Meeting - June 2 - 6, 2017 - Chicago, Illinois, USA

1. Rahbar K, et al. German Multicenter Study Investigating 177Lu-PSMA-617 Radioligand Therapy in Advanced Prostate Cancer Patients. J Nucl Med. 2017 Jan;58(1):85-90. doi: 10.2967/jnumed.116.183194. Epub 2016 Oct 20.