Seeking Alpha
Long only, biotech, healthcare, mid-cap
Profile| Send Message|
( followers)  
Georgia Health Sciences University (GHSU), in collaboration with Dendreon Corporation (NASDAQ:DNDN), recently initiated a new Phase 2 study under the direction of Principal Investigator Samir N. Khleif, MD, employing Dendreon's Provenge and two drugs shown to shrink tumors. The trial, known as 'Sipuleucel-T, CT-011, and Cyclophosphamide for Advanced Prostate Cancer,' is described on the clinicaltrials.gov Web site. Its objective is to test the effectiveness of Provenge (also known as Sipuleucel-T), CureTech's CT-011, and cyclophosphamide for prostate cancer.

According to the University's News and Information press release, preclinical animal studies performed in Khleif's lab found the combination of Provenge with these two other drugs led to a significant increase in survival and complete tumor regression in more than 50 percent of mice. [emphasis added] Based on these results, GHSU has begun the first human trial involving these three agents. It should be noted that cyclophosphamide, in a low dose, enhances the effect of Provenge and CT-011. Both have been safely used alone or in combination with other cancer therapies, but never for prostate cancer.

In the press release, Dr. Khleif said "[A]lthough the increased overall survival seen with Provenge treatment is a welcome advance in the treatment of prostate cancer, the goal of cancer therapy must be the eradication of disease. Therefore, improvements can be made, and this clinical trial is intended to improve the current standard of care."

The study protocol has two parts, each having different participants. All participants will be monitored with frequent blood tests and imaging studies.

Part I:

  • Participants will provide cells for the Sipuleucel-T treatment three times. The first time will be 3 days before the chemotherapy. The second time will be 10 days after chemotherapy. The third time will be 24 days after chemotherapy.
  • Participants will have one dose of cyclophosphamide the day before the first dose of Sipuleucel-T.
  • Participants will have Sipuleucel-T about 3 days after each cell donation.

Part II:

  • Participants will be in three groups: Sipuleucel-T given alone, given with CT-011, or given with both cyclophosphamide and CT-011.
  • Participants will provide cells for the Sipuleucel-T treatment three times, as in Part I.
  • Participants will have Sipuleucel-T about 3 days after each cell donation, and will receive treatment with the other drugs as directed by the study doctors.

The three arms of the study are shown below. Presumably, each arm will comprise 19 patients.

Arms

Assigned Interventions

Active Comparator: Arm A

Sipuleucel-T autologous active cellular immunotherapy only for 3 cycles (cycle = 14 days)

Other: Sipuleucel-T (Provenge)

Vaccine

Experimental: Arm B

Sipuleucel-T for 3 cycles (cycle = 14 days) + CT-011 (3mg/kg) IV infusion delivered over approximately 2 hours, 2 days after each Sipuleucel-T infusion

Drug: CT-011 (Anti-PD1 Antibody)

Immune Enhancer

Other: Sipuleucel-T (Provenge)

Vaccine

Experimental: Arm C

Sipuleucel-T for 3 cycles (cycle = 14 days) + cyclophosphamide (125 or 250mg/m2) IV [first cycle only] + CT-011 (3mg/kg) IV infusion delivered over approximately 2 hours, 2 days after each Sipuleucel-T infusion

Drug: CT-011 (Anti-PD1 Antibody)

Immune Enhancer

Other: Sipuleucel-T (Provenge)

Vaccine

Drug: Cyclophosphamide

Low dose- Immune Enhancer

The formal Objectives of the study are:

  • To assess the feasibility of administration of Provenge autologous active cellular immunotherapy in combination with low dose cyclophosphamide in men with advanced castrate-resistant (hormone refractory) prostate cancer.
  • To determine the immune efficacy of Provenge autologous active cellular immunotherapy alone vs. Provenge in combination with CT- 011 vs. Provenge in combination with low-dose cyclophosphamide and CT-011 on the change in PA2024-specific IFN-? ELISPOT responses in men with advanced, castrate-resistant prostate cancer.
  • Secondary objectives will determine the tolerability and toxicities of the combination of low-dose cyclophosphamide/CT-011/ Provenge and determine in a preliminary fashion whether this regimen correlates with increased progression-free survival (NYSE:PFS) and overall survival (OS) in patients and with growth rate in an exploratory fashion.

Cyclophosphamide (trade names Endoxan, Cytoxan, Neosar, Procytox, Revimmune), also is known as cytophosphane. A prodrug, it is converted in the liver to active forms having chemotherapeutic activity.

CT-011, a product of CureTech Ltd., is a humanized monoclonal antibody ((mAb)) that modulates the immune response, and inhibits tumor growth and the spread of metastases. According to the company, "[T]he efficacy of CT-011 was studied in a variety of experimental tumor models for leukemia/lymphoma, melanoma, lung, colon, fibrosarcoma, breast cancer and more. In all these models, single or multiple antibody doses administered 10-14 days post tumor inoculation, were able to inhibit tumor growth, to extend the survival of tumor-bearing mice, and to generate tumor-specific protection against tumor re-challenge." A Phase I, dose escalation, clinical study in 17 hematological malignancy patients has been completed.

Teva Pharmaceuticals (NYSE:TEVA) has been a major investor in CureTech.

The estimated completion date for the Georgia Health Sciences University Provenge study is December 2017. The final data collection date for primary outcome measure is estimate at December 2014.

Technical and Other Analyses

The Daily chart, courtesy StockChart.com, shows the stock closing last Friday at $4.87, one of only a handful of biotechs to close in the green on a lackluster day of trading in markets whose participants are preoccupied with the fiscal cliff. Interestingly, the Relative Strength is approaching overbought territory. The MACD is positive, suggesting the Smart Money has begun moving back into the issue. In part, this may be the result of analysts become cautiously optimistic 4Q12 revenues will show an improvement over those announced for 3Q12. Indeed, the average of 23 analyst revenue estimates for the quarter ending December 31, 2012 recently increased to $80.55 million. Whether or not this level of revenue will be achieved, of course, will not be known until late January, 2013. Finally, it is interesting to note the recent increase in DNDN stock shorted, something done, perhaps, by traders in anticipation of an announcement by the FDA regarding the approval of Johnson & Johnson's (NYSE:JNJ) Zytiga in Provenge's (prechemo) space.

The Weekly data tell a more muted story. The Relative Strength has now begun to rise from its Oversold condition while the MACD is neutral.

Disclosure: I am long DNDN. I wrote this article myself, and it expresses my own opinions. I am not receiving compensation for it (other than from Seeking Alpha). I have no business relationship with any company whose stock is mentioned in this article.

Additional disclosure: I am long both DNDN and the May 2013 $3 PUTS. I am not a registered investment advisor and do not provide specific investment advice. The information contained herein is for informational purposes only. Nothing in this article should be taken as a solicitation to purchase or sell securities. Before buying or selling any stock, do your own research and reach your own conclusion. Investing involves risks, including loss of principal.

Source: Dendreon: New Provenge Trial Involves Drugs Shown To Shrink Tumors