In a cancer vaccine setback, the drug giant GlaxoSmithKline (GSK) announced yesterday that an immunotherapy it had been testing in a phase III trial had flopped. The company is holding out hope, however, that some patients with a certain genetic signature will still be helped, and the trial is continuing.
The treatment “did not significantly extend disease-free survival … when compared to placebo” in volunteers with melanoma, the London-based company stated bluntly in its press release. Called MAGE-A3, the vaccine targets proteins by the same name that are expressed on tumor cells in a subset of patients. It’s supposed to stimulate the immune system to destroy those cells.
The likely problem with MAGE-A3 is one that a myriad of other cancer vaccines have not been able to overcome, says Steven Rosenberg, an immunotherapist and chief of the surgery branch at the National Cancer Institute in Bethesda, Maryland: It couldn’t prevent immune reactions that dampen the vaccine’s ability to mount a successful attack on tumors. “I thought there was a very tiny chance that this MAGE vaccine would have any impact,” Rosenberg says, “because no vaccine like it has been effective.”
GSK’s scientists—along with others—have been trying hard to predict exactly who might respond to immune therapies like MAGE-A3 and other cancer treatments generally. In July, the company’s researchers and some academic collaborators published a paper in the Journal of Clinical Oncology identifying an 84-gene “signature” that seemed to correlate with how well people with metastatic melanoma responded to the therapy. Now, says GSK spokesperson Melinda Stubbee, the company will test some variation of this signature I in the ongoing melanoma trial, which includes 1345 people. A data safety monitoring board is allowing the study to continue while that’s tested.
GSK also has a phase III lung cancer trial with MAGE-A3 and expects to report those results sometime next year. In a presentation to analysts and investors in late July, GSK’s chief executive officer, Andrew Witty, described MAGE-A3 as “high-risk but potentially high rewards.” He continued: “I’m not naïve, I’m completely open to the possibility that these programmes fail.”