793PD - Phase 1 study of the PSMA-targeted small-molecule drug conjugate EC1169 in patients with metastatic castrate-resistant prostate cancer (mCRPC)

Date 10 September 2017
Event ESMO 2017 Congress
Session Genitourinary tumours, prostate
Topics Drug Development
Prostate Cancer
Genitourinary Cancers
Personalised Medicine
Presenter Michael Morris
Citation Annals of Oncology (2017) 28 (suppl_5): v269-v294. 10.1093/annonc/mdx370
Authors M. Morris1, N.J. Vogelzang2, O. Sartor3, A. Armour4, M. Groaning5, R. Messmann6, A. Robarts7, D.P. Petrylak8, A. Tolcher9, M.S. Gordon10, H. Babiker11
  • 1Genitourinary Oncology Service, Memorial Sloan-Kettering Cancer Center, 10065 - New York/US
  • 2Medical Oncology, Comprehensive Cancer Centers of Nevada, 89169 - Las Vegas/US
  • 3Oncology, Tulane University, 70112 - New Orleans/US
  • 4Medical, Endocyte, Inc., Indianapolis/US
  • 5Clinical, Endocyte, 46268 - Indianapolis/US
  • 6Medical Oncology, Endocyte, 47906 - West Lafayette/US
  • 7Genitourinary Oncology Service, Memorial Sloan Kettering Cancer Center, New York/US
  • 8Medical Oncology, Yale University School of Medicine Medical Oncology, 06520-8032 - New Haven/US
  • 9Medical Oncology, South Texas Accelerated Research Therapeutics (START), 78229 - San Antonio/US
  • 10Medical Oncology, HonorHealth Research Institute, Scottsdale/US
  • 11Medical Oncology, University of Arizona Comprehensive Cancer Center, 85724 - Tucson/US

Abstract

Background

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancers, but not in most non-prostate normal tissues, making it a potential therapeutic target. EC1169, a PSMA-targeted conjugate of the microtubule inhibitor tubulysin B hydrazide is being studied in a two-part phase 1 dose escalation (A)/expansion (B) study in mCRPC. The utility of the PSMA-targeted companion imaging agent 99mTc-EC0652 is also being evaluated as a patient selection tool. Part A has been completed. We now report the part B data on pts treated to date.

Methods

EC1169 is administered as an IV bolus on days 1, 8 every 21 days. The RP2 dose of 6.5 mg/m2 was determined in Part A. Part B pts are treated at the RP2 dose and enrolled in 1 of 2 cohorts: mCRPC taxane naïve (cohort 1, 45 pts) or taxane exposed (cohort 2, 40 pts). Prior to treatment, pts undergo a 99mTc-EC0652 SPECT/CT scan. The primary endpoint of Part B is median radiographic progression-free survival (rPFS). Other study evaluations are OS, PSA, and CTC-based biomarkers.

Results

Thirty-four of a planned 85 pts in Part B have been treated (14 taxane naïve, 20 taxane exposed). Median age is 70 (range: 49-84). Median number of cycles is 3 (range: 1-7). Twenty-six pts (76.5%) reported at least 1 treatment related AE. Most treatment related AEs (TRAEs) are Gr1 and 2; G3 treatment-related constipation occurred in 1 pt. No Grade 4 TRAEs have been reported. No dose reductions due to AEs have occurred. Six of twelve evaluable taxane-exposed pts in Part B had stable disease or better at their first post-baseline scan (9 wks). One pt currently beyond the 18-week scan has achieved durable resolution of his soft tissue disease. Imaging with 99mTc-EC0652 suggests excellent disease localization.

Conclusions

The RP2 dose of EC1169 is 6.5 mg/m2 (D1, 8 every 21 days). EC1169 has been well tolerated in 34 Part B pts at the RP2 dose A PSMA-targeted therapeutic strategy appears viable. There is evidence of anti-tumor activity in both the taxane naïve and taxane exposed pts.

Clinical trial identification

NCT02202447

Legal entity responsible for the study

Endocyte, Inc.

Funding

Endocyte, Inc

Disclosure

A. Armour, M. Groaning: Employee of Endocyte, owns company stock. R. Messmann: Contractor for Endocyte, owns company stock. All other authors have declared no conflicts of interest.