After posting positive trends in interim data, Prima BioMed (NASDAQ: PBMD) is focusing on two final data readouts in the second half this year from a Phase 2b clinical trial of its CVac cancer vaccine to treat epithelial ovarian cancer patients in remission after first-line or second-line therapy.
"This will support long-term development of CVac," CEO Matt Lehman says in an interview with BioTuesdays.com, referring to final efficacy and intracellular cytokine staining ((ICS)) data, which are designed to explain the product's mechanism of action by showing T-cell activity against the tumor.
Since ovarian cancer is generally diagnosed at a late stage, only 20% to 30% of patients with late-stage disease survive for five years. "A maintenance treatment like CVac would be the first of its type in this new market. We believe the product has potential to achieve market penetration within the first year after it would be approved by regulators," Mr. Lehman contends. The global market for ovarian cancer therapy surpassed $1.2-billion last year.
CVac is an autologous dendritic cell immunotherapeutic intended for patients in remission. The vaccine is designed to stimulate a T-cell response to tumor cells that over-express a surface cell protein called mucin 1.
In the manufacturing process, dendritic cells - a subset of white blood cells - are isolated from a patient's blood, separated and matured in a lab, then cultured with a mucin 1 protein before being formulated as 1 ml cryo-frozen vials for reinjection into the patient. Manipulating dendritic cells outside of a patient's own body allows the cells to overcome the evasive mechanisms of the tumor.
When a dendritic cell encounters foreign material, it generates a recognition signal and triggers the immune system to respond by activating another subset of blood cells called cytotoxic or killer T-cells. These cells then respond by killing the foreign material.
Last October, in interim data for its 63-patient Phase 2b trial being conducted in the U.S. and Australia, Prima said there were no therapy-related toxicity issues. Progression-free survival data showed a favorable trend toward patients receiving CVac, who stayed in remission longer than those in the standard of care group.
Combining overall data of first and second remission, the median progression-free survival time was 421 days for non-randomized CVac patients, 365 days for CVac patients and 321 days for patients on standard of care. The first seven patients on the study were not randomized, and all seven were assigned to receive CVac at the request of the FDA as a small safety sample.
In a report, Nomura Equity Research said the interim data support the continued development of CVac. "We note that CVac should confer increasing benefit to patients as the trial continues because the immune system generally takes time to build up its strongest response against tumor cells. Hence, we expect CVac treatment progression-free survival to increase during the rest of the trial."
Mr. Lehman points out that the interim progression-free survival and immune monitoring data from the Phase 2b trial demonstrate an early profile similar to other successful immunotherapies such as Dendreon's (DNDN) Provenge, an advanced prostate cancer treatment, and Bristol-Myers Squibb's (BMY) Yervoy for the treatment of melanoma that has spread.
"These immunotherapies work best and will work best in patients with a low tumor burden," Mr. Lehman maintains. "After multiple injections of these immune therapies, what you start to see is a separation in the outcome for the control group and the treatment group. We're pretty happy with the interim data, even though it was from a small cohort of patients. And there are no impediments to moving the CVac clinical development program forward."
As a result, Prima intends to enroll an estimated 800 patients in a Phase 2/3 CANVAS clinical trial at some 120 sites in the U.S., Australia, Asia and Europe. Patients must be in complete clinical and radiologic remission after first-line surgery and chemotherapy to participate in the 44-week study, which is expected to report final data in 2015.
Mr. Lehman says the ongoing Phase 2b study also established a "consistency in our manufacturing" of CVac between the U.S. and Australia. An important goal of the CANVAS study will be to validate and plan for a commercial-ready global manufacturing process, including in its newest center in Germany. "We've talked to some potential partners, and they will depend on us to provide a scalable manufacturing solution in addition to clinical data," he adds.
The goals of the CANVAS study are to confirm longer-term safety of CVac, establish efficacy by progression-free survival and overall survival, investigate CVac's impact on quality of life factors and explore certain biomarkers and cellular activity.
The company also will attempt to validate a companion mucin 1 diagnostic test in a larger patient population during CANVAS, which Mr. Lehman says is part of the company's commercialization strategy. "The diagnostic is designed to make sure patients are over-expressing the mucin 1 target before they receive CVac and to assure we are treating the right patients."
Mr. Lehman suggests that if overall survival in the CANVAS trial is statistically significant, CVac could be approved on the one trial. He adds that if there is a significant improvement only in progression-free survival, European regulators have indicated CVac would be considered for marketing approval but that the FDA may be a bit more reluctant.
He also points out that the company is likely to pursue serious partnering discussions starting in 2014 after all of the Phase 2b data are in, including evidence of CVac's mechanism of action, and after the CANVAS trial is well underway globally and manufacturing, logistics and quality control procedures have been developed to scale in the U.S., Australia and Europe.