Phase III Immunotherapy Lung Cancer Trial Stopped Early

GlaxoSmithKline has stopped a phase III trial of a novel lung cancer immunotherapeutic agent, after determining that it may not be possible to identify which genetic subgroups may benefit from the treatment.

Vincent Brichard, the senior vice-president and head of immunotherapeutics at the company said in a press release that they are “extremely disappointed” that there was no positive outcome in the trial. The MAGRIT trial was designed to test the MAGE-A3 immunotherapeutic in non-small-cell lung cancer (NSCLC) patients. All patients had completely resected stage IB, II, or IIIA NSCLC, and all tumors expressed the MAGE-A3 gene. They received up to 13 doses of the immunotherapeutic delivered intramuscularly, or placebo.

According to data the company released toward the end of March, the trial did not meet either of its co-primary endpoints. The cancer vaccine, as it is commonly known, did not significantly extend disease-free survival compared to placebo in the overall MAGE-A3-positive population, nor did it extend disease-free survival in patients who did not receive chemotherapy (the second co-primary endpoint).

Following those failures, the company continued to see if a third endpoint was met: disease-free survival in a gene signature-positive sub-population, to determine potential groups that might benefit from the agent. The analysis, however, showed that this endpoint is “not feasible due to an insufficient treatment effect.”

The trial was very large, with an enrollment of 2,278 patients listed at ClinicalTrials.gov. According to the press release, the data will now be unblinded for further analysis. “We hope that the data generated in this trial will advance our understanding of the science of immunotherapeutics, and ultimately toward development of new therapies,” Brichard said in the release.

The MAGE-A3 vaccine is not completely dead, however. GlaxoSmithKline will continue testing the agent in the DERMA trial, in melanoma patients. Just as with the NSCLC trial, DERMA’s inclusion criteria specify that all patients must undergo complete surgical resection prior to enrollment. That trial has an enrollment of more than 1,300 patients, with an estimated completion date of late 2016. It will also assess disease-free survival, and will also seek a genetic signature of patients that might benefit most from the immunotherapeutic.