Aduro Biotech says its leading clinical trial for its cancer-fighting combination of GVAX and CRS-207 was a flop. The biotech reported this morning that its combo not only failed to hit the primary endpoint, it did worse than the two solo groups in the study.
“Median overall survival (MOS) in this third-line and greater setting was 3.8 months for patients treated with the immunotherapy regimen of CRS-207 and GVAX Pancreas, 5.4 months for patients treated with CRS-207 alone and 4.6 months for patients administered chemotherapy,” the company reported.
Aduro's stock ($ADRO) plunged 30% on the news in premarket trading.
“While we are well aware of the very difficult-to-treat nature of late-stage metastatic pancreatic cancer, we are surprised by the divergence of these data from the results of our Phase 2a study,” said CEO Stephen Isaacs. But the company hasn't given up hope on its lead program.
“In the overall survival analysis, we were intrigued by activity seen with CRS-207 as a single-agent. While the median duration of 5.4 months appears greater for CRS-207, the overall survival curve of CRS-207 alone was comparable to overall survival seen with chemotherapy. Of note, due to a disproportionately high dropout rate in the single-agent chemotherapy arm, most of these patients instead received a variety of combination treatments, including chemotherapies, immunotherapies and targeted therapies,” said Dirk Brockstedt, executive vice president, research and development for Aduro.
In a conference call with analysts Aduro execs noted that they are now shelving plans for a pivotal Phase III study in pancreatic cancer, focusing on an ongoing study in the pipeline that includes a checkpoint inhibitor.
The history of cancer vaccines not customized to individual patients has been a litany of failure, with programs for Stimuvax and others experiencing a string of defeats in the clinic. Celldex joined that circle of failure recently with a Phase III miss for Rintega. Aduro, though, doubled down on the cancer vaccine strategy and was able to strike some big-money pacts along the way on the basis of some promising midstage data.
GVAX Pancreas is based on a pancreatic cell line modified to secrete granulocyte-macrophage colony-stimulating factor (GM-CSF), a cytokine known to stimulate the immune system. CRS-207 is made up of attenuated (deactivated) Listeria monocytogenes that express mesothelin, sparking another immune response to a protein concentrated on pancreatic cancer cells. Together, they’re supposed to provide a one-two punch against cancer, with an option to add on additional drugs to continue to build an attack on cancer cells.
That was the only workable strategy with GVAX, which, like other cancer vaccines, wasn’t able to spur a strong enough response to make a significant difference in the fight against cancer as a solo therapy, allowing Aduro to buy it for a song in early 2013. Monday's conference call included several skeptical remarks from analysts about GVAX's future, if any.
Aduro was on hand at the 2013 ASCO confab to review the data from a midstage study involving 93 patients with advanced pancreatic cancer. A combination of chemo plus GVAX pancreas and CRS-207 significantly outperformed GVAX and chemo, bumping up overall survival from 3.9 months to 6.1 months. That's not a big gain, but it was a sign of progress in a very tough field. And it was good enough for the FDA to grant a breakthrough drug designation.
Now the company is forced into a classic defensive crouch, citing its significant cash reserves as it looks to regroup.
- here's the release