Shares of Australia’s Prima Biomed Ltd. were jolted Wednesday after top-line data from the company’s Phase II study of cancer vaccine candidate Cvac showed no observed difference in estimated median progression-free survival (PFS) compared to control in epithelial ovarian cancer patients in first or second remission. On the Nasdaq Global Market – the first of the company’s public markets to react to the news – shares (NASDAQ:PBMD) fell 74 cents, or 31.3 percent, to close at $1.61.

Separate estimates of median PFS by stage of remission were inconclusive, favoring the control arm compared to Cvac for patients in first remission and Cvac for patients in second remission. Neither trend was statistically significant.

On the plus side, the autologous dendritic cell-based product was well tolerated, with no serious adverse events considered related to protocol therapy. Most nonserious adverse events were mild and transient in nature.

In addition, immune monitoring data indicated Cvac induced a T-cell response that may prove beneficial in treating ovarian cancer, and the data showed no evidence of antibody response after Cvac administration.

The data, though early, showed once again the challenges biopharmas face in designing trials that demonstrate the therapeutic value of cancer vaccines. Just two weeks ago, London-based Glaxosmithkline plc reported cancer immunotherapy candidate MAGE-A3 failed to significantly extend disease-free survival in melanoma patients compared to placebo in the Phase III DERMA trial. (See BioWorld Today, Sept. 6, 2013.)

Prima, based in Sydney, sought to put a positive spin on the CAN-003 findings, emphasizing the trial was not adequately powered to detect statistical significance in PFS. In addition to MAGE-A3, other cancer immunotherapeutics have reported inconclusive PFS data during clinical studies, including marketed products Provenge (sipuleucel-T, Dendreon Corp.) and Yervoy (ipilimumab, Bristol-Myers Squibb Co.), said company CEO Matthew Lehman.

“What we’re seeing is not unlike most other cancer immunotherapies, where endpoints like response rate or progression-free survival or disease-free survival just simply don’t seem to give us very much information,” Lehman told BioWorld Today. “We do see a product that is very well tolerated. It is immunologically active, so we’re very comfortable that this product is helping patients and we’re getting the right kind of immunological or biological response.”

Lehman conceded, however, that the company must wait longer to see how that activity translates clinically and affects overall survival (OS), where data are still immature. OS generally has been favored by the FDA as an endpoint in cancer therapies and served as the basis for marketing approvals for Provenge and Yervoy.

“We’ve actually been a little surprised by the low number of deaths, thus far, on the study,” Lehman said, estimating mature OS data could be a year away.

In the meantime, the company said additional information from CAN-003 will be presented at the European Cancer Congress in Amsterdam on Oct. 1 , followed by a management conference call to discuss the Phase II results in greater detail.

Still, jitters were understandable considering the impact of potential delays to the lead program, in which the company has invested the lion’s share of resources. The biggest immediate effect was the suspension of enrollment in the pivotal Phase III CANVAS trial of Cvac, already under way in multiple countries, which was designed with PFS as the primary endpoint.

“We don’t see any reason to withdraw patients,” Lehman said. “We don’t see any safety concerns. But, clearly, having PFS as the endpoint is something we have to change.”

The company will meet with regulators to discuss an amended clinical development plan for CANVAS that includes a new primary endpoint and, potentially, a different enrollment target to generate an appropriate clinical signal.

“The product is having the right kind of activity in the patient,” Lehman said. “It’s really a question of finding the right endpoint to evaluate clinical benefit.”

Prima did not identify any specific genetic marker or baseline patient criteria to suggest Cvac should be targeted to a particular subset of epithelial ovarian cancer, Lehman said, noting that the company will continue to examine individual patient profiles in more detail.

“The key message here is that the [CAN-003] data are not negative,” he added. Although inconclusive data may hamper the company’s ability to use PFS as a potential surrogate endpoint, “it doesn’t really affect the overall clinical development plan and the potential to benefit patients and extend survival.”

In addition to Cvac, a half-dozen immunotherapy candidates targeting ovarian cancer are in Phase II or registration studies, according to Thomson Reuters Cortellis Competitive Intelligence. They include candidates from Galena Biopharma Inc., Gradallis Inc., Mabvax Therapeutics Inc., Immunovaccine Inc., Avax Technologies Inc. and Quest Pharmatech Inc.

Lehman said Prima has sufficient resources to see Cvac to the end zone, including approximately A$30 million (US$28.6 million) in the bank and two nondilutive research grants.

“There’s no immediate pressure on our financial situation,” he said. “We do have appropriate space to make the adjustments and move forward.”