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

Date

09 Oct 2016

Session

Poster display

Presenters

Michael Morris

Citation

Annals of Oncology (2016) 27 (6): 243-265. 10.1093/annonc/mdw372

Authors

M.J. Morris1, N.J. Vogelzang2, O. Sartor3, A. Armour4, D. Petrylak5, A. Tolcher6, S. Ejadi7, H.M. Babiker8

Author affiliations

  • 1 Medical Oncology, Memorial Sloan-Kettering Cancer Center, 10065 - New York, NY/US
  • 2 Medical Oncology, US Oncology Research c/o Comprehensive Cancer Crts of NV, Las Vegas/US
  • 3 Dept. Of Medicine & Urology, Tulane University, 70112 - New Orleans/US
  • 4 Clinical, Endocyte, Inc, 46268 - Indianapolis/US
  • 5 Medical Oncology, Smilow Cancer Hospital at Yale-New Haven, 208032 - New Haven/US
  • 6 Clinical Research, START - South Texas Accelerated Research Therapeutics, LLC, 78229 - San Antonio/US
  • 7 Clinical Trials, Virginia G. Piper Cancer Center at Scottsdale Healthcare, 85258 - Scottsdale/US
  • 8 Clinical Oncology, Honor Health, Scottsdale/US
More

Resources

Background

Prostate-specific membrane antigen (PSMA) is overexpressed by most prostate cancers. EC1169 is a conjugate of a PSMA targeting moiety linked to the cytotoxic agent tubulysin B hydrazide (TubBH). Following internalization of EC1169 by targeted cancer cells, intracellular release of TubBH results in inhibition of tubulin polymerization. In PSMA-positive LNCaP and MDA PCa 2b xenografts, complete responses and cures have been observed following EC1169 treatment. EC1169 does not show activity in PSMA-negative models, demonstrating its specificity. EC0652 is a companion radiodiagnostic conjugate of a 99mTc chelator and a PSMA-targeting moiety designed to characterize PSMA-expressing disease in real time. Rapid tumor uptake of 99mTc-EC0652 and rapid normal tissue clearance result in enhanced tumor: background ratios with SPECT imaging.

Methods

Key inclusion criteria are age ≥18 years, ECOG PS 0–1, and adequate organ function. Patients (pts) must have failed androgen-deprivation therapy, progressed on abiraterone or enzalutamide, and have been previously treated with a taxane unless contraindicated. Patients are to undergo a 99mTc-EC0652 SPECT scan prior to therapy. PSMA positivity is not a requirement for study entry. EC1169 is administered as an intravenous bolus on Days (D) 1, 8 (QW) every 21 D. Dose escalation is based upon the “3 + 3” method. Study objectives include determination of EC1169 MTD and recommended phase II dose, safety, pharmacokinetics, antitumor activity and its correlation with PSMA expression as identified on 99mTc-EC0652 SPECT imaging.

Results

23 pts have been treated on the QW schedule. Median age is 70 (range: 57-82). The median number of administered EC1169 cycles is 2 (range: 1-11). 12 (52%) treatment related AEs have been reported. Most common Grade 3/4 AEs were anaemia (2; 8.7%) and lymphopenia (2; 8.7%). No DLT, related SAEs or toxicity requiring dose reductions occurred. PSA response (≥50% max decline) has been observed in 2 pts. Data will be updated at the meeting.

Conclusions

To date, EC1169 has been well tolerated. There are promising signs of early efficacy in this heavily pre-treated population.

Clinical trial identification

ClinicalTrials.gov NCT02202447

Legal entity responsible for the study

Endocyte, Inc.

Funding

Endocyte, Inc.

Disclosure

M.J. Morris: MSKCC receives funding from Endocyte for the conduct of this study. I've received funding for advisory boards from Progenics, Tokai, & Millennium Pharmaceuticals. I'm an uncompensated advisor for Bayer, which my institution also receives funding. O. Sartor, D. Petrylak: Endocyte: consultancy fees.

A. Armour: Alison Armour is an employee of Endocyte. H.M. Babiker: Endocyte: consultancy fees. Celgene: Consultant/Advisory Board. SirTex: Honorarium. All other authors have declared no conflicts of interest.

Resources from the same session

This site uses cookies. Some of these cookies are essential, while others help us improve your experience by providing insights into how the site is being used.

For more detailed information on the cookies we use, please check our Privacy Policy.

Customise settings