Introduction

Identification of prostatic tissue from non-prostatic tissue can help preserve potency, continence, as well as decrease positive margins. PSMA, a transmembrane glycoprotein expressed by neoplastic prostate epithelium, is a possible target for identification of prostate tissue. MDX1201, an investigational new drug (IND) composed of fully human IgG with conjugated fluorescent marker (AlexaTM488) with specificity against PSMA was safely administered in mice models. The antibody-fluorescent dye complex was shown to bind to cells expressing PSMA demonstrating significant staining of prostatic adenocarcinoma. We performed the first in-human FDA-approved phase I 3+3 dose finding study of intravenously (IV) administered MDX1201 in intermediate- to high-risk patients undergoing RARP and extended lymph node (LN) dissection.

Methods

Patients received a single intravenous infusion of MDX1201 four days prior to RARP to allow for safety evaluation. A 488 nanometer laser was attached to the da Vinci Si surgical robot camera at the time of RARP to allow for visualization of fluorescent dye marking presence of prostatic cancerous tissue. 5 mg dose was given to the first 3 patients, and then the dose was escalated to 15 mg provided safety considerations permit. Patients with prior prostate cancer treatment were excluded.

Results

MDX1201 was successfully administered to 5 patients, with no adverse events observed. Initial 5 mg dose failed to show visualization of fluorescent dye in first 3 patients. Of the 15 mg dose patients, patient #4 demonstrated fluorescence ex vivo within the sectioned prostate that correlated with pathological findings, while patient #5 demonstrated fluorescence in-vivo with mild prostatic fluorescence at the right apex, left apex, left mid, and also moderate fluorescence demonstrated at the right external iliac LNs. For patient #5, histopathologic examination confirmed tumor to the mid right lobe (dominant nodule), with a minor focus in anterior left lobe near the base. There was no LN metastasis in this patient (pT2cN0). In the five patients (median PSA 9.5, 80% intermediate-risk, 100% > pT2c), the median LN yield was 18 with no LN involvement in any patient. No positive margins were detected.

Conclusions

We demonstrate the first in human study using an anti PSMA antibody demonstrating fluorescence in the prostate. Identification of prostatic tissue using a conjugated fluorescent marker with specificity against PSMA may help guide preservation of critical structures.

Funding

None