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Original Investigation
July 5, 2018

Safety and Efficacy of BIND-014, a Docetaxel Nanoparticle Targeting Prostate-Specific Membrane Antigen for Patients With Metastatic Castration-Resistant Prostate CancerA Phase 2 Clinical Trial

Author Affiliations
  • 1Genitourinary Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York
  • 2Department of Medicine, Weill Cornell Medicine, New York, New York
  • 3Department of Medicine and Urology, University of Virginia School of Medicine, Charlottesville
  • 4Department of Solid Tumor Oncology, Cleveland Clinic, Cleveland, Ohio
  • 5Division of Hematology and Oncology, Department of Medicine, University of Michigan Health System, Ann Arbor
  • 6Florida Cancer Specialists, Fort Myers
  • 7Division of Hematology and Oncology, Department of Medicine, University of North Carolina, Chapel Hill
  • 8Division of Hematology and Oncology, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, California
  • 9Division of Hematology and Oncology, Department of Medicine, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco
  • 10Epic Sciences, Inc, San Diego, California
  • 11Bind Therapeutics, Inc, Cambridge, Massachusetts
JAMA Oncol. Published online July 5, 2018. doi:10.1001/jamaoncol.2018.2168
Key Points

Questions  What is the safety and efficacy of BIND-014, a docetaxel-containing nanoparticle targeting prostate-specific membrane antigen (PSMA), in metastatic castration-resistant prostate cancer, and does PSMA expression on circulating tumor cells decrease with treatment?

Findings  In this phase 2 clinical trial of 42 chemotherapy-naive patients receiving BIND-014 therapy for metastatic castration-resistant prostate cancer, the median radiographic progression-free survival was 9.9 months. The most common adverse events were fatigue. nausea, and diarrhea.

Meaning  Tumor cell death was associated with PSMA expression on circulating tumor cells, which, if validated, could serve as a pharmacodynamic response measure and help select patients with metastatic castration-resistant prostate cancer who are most likely to benefit from PSMA-directed treatment.

Abstract

Importance  Preferential delivery of docetaxel to tumors by prostate-specific membrane antigen (PSMA)–targeted nanoparticles is clinically effective, and the selective reduction of PSMA-positive circulating tumor cells (CTCs) after treatment has implications for patient selection and disease monitoring.

Objective  To determine the safety and efficacy of BIND-014, a PSMA-directed docetaxel-containing nanoparticle, in patients with metastatic castration-resistant prostate cancer (mCRPC).

Design, Setting, and Participants  A multicenter open-label, phase 2 clinical trial of 42 chemotherapy-naive patients with progressing mCRPC after treatment with abiraterone acetate and/or enzalutamide was conducted from June 24, 2013, to June 10, 2016.

Intervention  Treatment with BIND-014 at a dosage of 60 mg/m2 was given intravenously on day 1 of 21-day cycles in combination with prednisone until disease progression or unacceptable toxic effects occurred.

Main Outcomes and Measures  The primary end point was radiographic progression-free survival according to Prostate Cancer Working Group 2 recommendations and Response Evaluation Criteria in Solid Tumors, version 1.1. Secondary end points included prostate-specific antigen (PSA) response (≥50% reduction from baseline) and changes in CTC number (from ≥5 to <5 cells per 7.5 mL of blood) (CellSearch). Changes in CTC number based on PSMA expression levels on CTCs were also evaluated (Epic Sciences).

Results  Among the 42 patients (81% white), the median age was 66 (range, 50-85) years, and median number of doses received was 6 (range, 1-21). A PSA response was observed in 12 of 40 patients (30%; 95% CI, 18%-45%), measurable disease response in 6 of 19 (32% [95% CI, 15%-54%]), and CTC conversions in 13 of 26 (50%; 95% CI, 32%-68%). Median radiographic progression-free survival was 9.9 (95% CI, 7.1-12.6) months. With use of the Epic Sciences non-EPCAM-based CTC detection platform, CTCs were detected in 16 of 18 patients (89%); 11 of 18 (61%) had CTCs with PSMA expression above the analytical threshold level (PSMA positive) at baseline (range, 0.4-72.4 CTCs/mL). After treatment, PSMA-positive CTCs were preferentially reduced. Treatment-related adverse events included grade 1 or 2 fatigue (29 of 42 patients [69%]), nausea (23 [55%]), neuropathy (14 [33%]), and neutropenic fever (1 [2%]).

Conclusions and Relevance  These findings suggest that treatment with BIND-014 is active and well tolerated in patients with chemotherapy-naive mCRPC. Antitumor activity may be related to PSMA expression levels on CTCs, which suggests that patients who are likely to benefit from this treatment can be identified before treatment is initiated.

Trial Registration  ClinicalTrials.gov Identifier: NCT01812746

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