Biomira Inc. started off 2007 by initiating two clinical trials: a Phase III non-small-cell lung cancer (NSCLC) trial with cancer vaccine Stimuvax, and a Phase II pancreatic cancer trial with thioredoxin inhibitor PX-12.
The Stimuvax protocol was green-lighted by the FDA under a special protocol assessment and reflects input from the European Medicines Evaluation Agency (EMEA).
The primary endpoint of the randomized, double-blind, placebo-controlled trial is survival, with secondary endpoints including time to symptom progression; time to progression; one-, two- and three-year survival; and safety.
More than 1,300 unresectable Stage III NSCLC patients will be enrolled, all of whom have exhibited a response or stable disease after at least two cycles of platinum-based radio-chemotherapy.
The main difference between the design of the current Phase III trial and that of Biomira's previous Phase IIb trial is the patient population. The Phase IIb trial enrolled patients with Stage IIIb and Stage IV NSCLC, and the resulting data were not statistically significant. Yet data from a pre-stratified subset of Stage IIIb patients demonstrated a median survival of 30.6 months for patients treated with the vaccine, compared to 13.3 months for those in the control group.
The Phase III trial will look at the patient group in which the survival advantage was noted during Phase II,' said Robert Kirkman, president and CEO of Biomira.
Kirkman added that patients in the trial will be allowed to have any best standard of care' in addition to Stimuvax, or as a control, which he anticipates will result in data showing how Stimuvax interacts with new lung cancer treatments such as Avastin (bevacizumab; Genentech Inc.) and Tarceva (erlotinib, Genentech Inc. and OSI Pharmaceuticals Inc.).
While Avastin inhibits angiogenesis, the blood vessel formation necessary for tumor growth, Stimuvax (BLP25 liposome vaccine) is designed to stimulate a T-cell immune response to cancer. The vaccine consists of a synthetic 25-amino acid sequence of the MUC1 protein antigen, which is over-expressed in several types of cancer, along with an adjuvant encapsulated in Biomira's proprietary liposomal delivery system. The mechanisms may potentially be complementary,' Kirkman said.
According to the ClinicalTrials.gov website, the trial should wrap up around December 2008. Enrollment is open in 12 countries, including the U.S., and will expand to 18 others. The enrollment of the first patient is expected this month and will trigger a milestone payment to Biomira from partner Merck KGaA.
Edmonton, Alberta-based Biomira and Darmstadt, Germany-based Merck initially joined forces in 2001 and have since shared North American development costs of Stimuvax, with Merck footing the bill for trials elsewhere. In January of last year, the companies restructured their deal, with Merck taking over all development and commercialization costs and responsibilities, including the Phase III Stimuvax trial, which it is conducting with U.S. affiliate EMD Pharmaceuticals Inc. (See BioWorld Today, May 4, 2001.)
The upcoming enrollment milestone will be Biomira's first payment related to Stimuvax to emerge from the deal, Kirkman said.
While its partner manages the Stimuvax trial, Biomira plans to keep busy conducting its own clinical trials with PX-12, the No. 2 product candidate in its pipeline. On Tuesday, Biomira kicked off a randomized, open-label Phase II study that will evaluate two dose levels of PX-12 in advanced pancreatic cancer patients whose tumors have progressed despite treatment with gemcitabine or gemcitabine-containing regimens.
The trial will be funded partially by the National Cancer Institute and will enroll up to 80 patients, with the first expected to be treated this month.
Biomira obtained PX-12 through its acquisition of Tucson, Ariz.-based ProlX Pharmaceuticals Corp. late last year. The drug is a first-in-class small molecule inhibitor of thioredoxin, a protein that regulates several transcription factors and has been linked to the aggressive proliferation of solid tumors including colon, lung and gastric cancers. In addition to the Phase II trial, PX-12 is being studied in an ongoing Phase Ib trial in advanced gastrointestinal cancers. A completed Phase I trial in metastatic cancer showed the drug to be well tolerated, with seven of 38 patients achieving stable disease of up to 322 days. (See BioWorld Today, Nov. 1, 2006.)
Also slated to begin clinical trials in the first half of 2007 is PX-478, another cancer drug obtained through the ProlX acquisition. PX-478 is a first-in-class inhibitor of hypoxia inducible factor-1a (HIF-1a), a protein involved in angiogenesis. Its entry into the clinic will be followed before the end of the year by one of three preclinical cancer programs: BGLP-40, a derivative of Stimuvax with a slightly modified antigen; PX-866, a PI-3-kinase inhibitor; or PX-316, an Akt-mediated survival signaling inhibitor.