Dr. Tagawa Presents Updated Results of ATL101 at AACR

At the annual American Association for Cancer Research in Washington, DC last week, Dr. Scott Tagawa presented updated combined analysis of 4 Phase I and Phase II studies involving 114 patients treated with ATL101. The analysis demonstrated that PSMA imaging might be used to predict the response to ATL101 radioimmunotherapy.ATL101 is a new targeted radiotherapy experimental drug for treating prostate cancer. ATL101 combines the humanized J591 monoclonal antibody targeting prostate-specific membrane antigen (PSMA) plus the Lutetium-177 radioisotope, creating the first tumor-specific delivery system able to target radiation to radio-sensitive prostate cancer cells wherever they are in the body.

From the sponsor’s press release:

14 patients were evaluable for semi-quantitative analysis of planar gamma images acquired after injection of ATL101 (35 patients from phase I at dose of 10-75 mCi/m²; 47 patients from Phase II at dose of 65-70 mCi/m² and 39 patients from phase I with a fractionated schedule at dose of 40-90 mCi/m²). 22 patients were also evaluable after injection of Indium-111 labeled J591 and treatment by Yttrium-90 labeled J591 at dose of 5-20mCi/m². Patients were sorted into 3 groups: low PSMA expression group included one third of patients, with no uptake (18%) or with weakly positive images (16%); high PSMA expression group included one half of patients, with tumor image as intense (26%) or more intense (24%) than liver. The 16 % remaining patients had intermediate uptake.

Significant correlation was found between higher PSMA expression (high vs. low) and higher response rates (RR) to treatment defined as >30% decline in PSA (RR=32% vs. 12.5%, p=0.01). RR was itself significantly correlated to longer survival. An association between PSMA expression by imaging and reduction in circulating tumor cell counts was also found (p=0.07). Further studies will examine quantitative molecular imaging with anti-PSMA PET/CT as recently published in animal models (Morris et al, 2013 ASCO Genitourinary Cancers Symposium).

Click here to read the complete press release.

Weill Cornell Researchers: Encouraging Results from J591 Study

Dr. Tagawa
Dr. Tagawa

Weill Cornell researchers recently published findings from a Phase II study of the lutetium-177-labeled monoclonal antibody J591 (called Lu-J591).

J591 is a man-made monoclonal antibody that is able to recognize a protein antigen (PSMA) expressed on virtually all prostate cancer cells, and more so in men with treatment-resistant metastatic disease. When a tiny tag of radioactive material is attached to the J591 antibody, that specifically targets prostate cancer cells, and delivered systemically this is known as “radioimmunotherapy.” Dr. Scott Tagawa and colleagues at Weill Cornell have been conducting clinical trials of the precision radioimmunotherapeutic J591 to determine its ability to eradicate prostate cancer cells.

In the recently published study, 47 prostate cancer patients with PSA progression after hormonal therapies with or without chemotherapy were treated with Lu-J591. 10.6 percent experienced more than 50% PSA decline, and 36.2% experienced more than 30% decline. Among those treated at the maximum tolerated dose, 46.9% had more than 30% PSA decline. Furthermore, 75% of patients with radiographically measurable disease had some measure of disease control; 67% of those assessed for circulating tumor cells had more than 50% decline in tumor cell counts 4 to 6 weeks after treatment.

The researchers concluded that a single dose of Lu-J591 was well tolerated and they found a measurable response rate. The authors conclude that Lu-J591 is a promising new therapeutic strategy to explore.

Click here to read the published abstract. Click here to read an article about the study and the findings.

Weill Cornell Researchers Create Device to Collect Living Prostate Tumor Cells; Potential to Inform Development of New Drugs

Cancer metastases (spreading from the initial cancer tumor to other parts of the body) account for the majority of cancer-related deaths because of poor responses to anti-cancer therapies.

Researchers at Weill Cornell Medical College, in collaboration with engineers from Cornell University in Ithaca, NY, have created a new device that searches the blood for living, circulating tumor cells. The device allows researchers to capture and molecularly characterize circulating tumor cells (CTCs) isolated from castrate-resistant prostate cancer patients (CRPC) receiving taxane chemotherapy. This new device will allow physicians to monitor drug response at the cellular level, which will potentially allow physicians to tailor prostate cancer treatments to an individual patient. The device is the first functional assay of a microtubule-targeting agent on living circulating tumor cells microfluidically extracted from patient blood.

The researchers  include Dr. Brian Kirby at Cornell University and  Dr. Paraskevi Giannakakou, Dr. Neil Bender, Dr. Scott Tagawa and Dr. David Nanus at Weill Cornell Medical College.

Background

Circulating tumor cells are prostate cancer cells which have escaped from prostate tumors (from the prostate, bone, or other areas) and are circulating in blood.  The FDA has cleared a specific type of test to enumerate (or count) the number of these cells in a tube of blood, called the CellSearch test.  The advantage of this test is that it has been well studied at many centers and has been validated to yield prognostic information.  However, this test is not very sensitive; men with metastatic prostate cancer may have no detectable cells.  In addition, this test is not specific to prostate cancer – the same test also picks up different cells (it is also cleared for breast and colon cancer).

The New Device

The collaborating researchers at Weill Cornell and Cornell University developed a new test called the “Geometrically Enhanced Differential Immunocapture” device. The device has been optimized based upon flow and size characteristics of prostate cancer cells.  Importantly, the device uses additional technology developed at Weill Cornell, a monoclonal antibody against Prostate Specific Membrane Antigen (PSMA).  The anti-PSMA antibody called J591, developed by Dr. Neil Bander in the Weill Cornell Department of Urology,  specifically recognizes the PSMA protein which is present on the surface of virtually all prostate cancer cells.  The combined technology has allowed Weill Cornell researchers to collect and analyze more prostate cancer cells than the standard device.

In addition to prognostic information, it is hoped that the capture and analysis of CTCs may serve as a type of “liquid biopsy” to allow researchers to gain information about a patient’s tumor.  Initial work has led to promising results in the ability to predict future responses to chemotherapy based upon a blood test prior to the drug or after only 1 dose.

The authors write, “these measurements constitute the first functional assays of drug-target engagement in living circulating tumor cells and therefore have the potential to enable longitudinal monitoring of target response and inform the development of new anticancer agents.”

Click here to read the published research paper.