Generex Biotechnology is planning a Phase 2 trial to test a combination of its AE37 peptide vaccine and Keytruda (pembrolizumab) in patients with advanced triple-negative breast cancer, after the U.S. Food and Drug Administration approved its investigational new drug application.

The study will be conducted under a collaborative agreement with Merck (known as MSD outside the U.S. and Canada) and the NSABP Foundation.

“We are gratified to see this important trial moving forward,” Eric von Hofe, president of Generex subsidiary NuGenerex Immuno-Oncology, said in a press release. “While we have tested AE37 in breast and prostate cancer patients, there is good rationale for inclusion of AE37 in the treatment regimen of a variety of additional cancer types of high unmet need.”

AE37 is an investigational anti-cancer vaccine that combines a small portion of the HER2 protein, found in about 80% of breast cancers, with GM-CSF, a protein that activates immune T-cells. The approach helps the immune system recognize HER2 as foreign and promote responses that might more robustly kill cancer cells.

The FDA’s decision was based on results from a previous Phase 2 trial (NCT00524277) in patients with breast cancer, where the AE37 vaccine was safe and well-tolerated, and induced a strong immunity against the HER2 protein. Patients receiving the vaccine in combination with GM-CSF also lived longer without signs of disease than those who received GM-CSF alone.

Interestingly, researchers found that the vaccine was particularly effective among some subgroups of patients, including those with triple-negative breast cancer, in whom AE37 reduced the risk of relapse by 74%.

Keytruda, an inhibitor of the PD-1 checkpoint protein, has also demonstrated benefits in these patients regardless of whether they had received prior treatment. In a Phase 2 trial (NCT02447003), 26% of previously treated patients achieved at least disease stabilization and 40% of untreated patients experienced the same outcome.

Researchers are now expecting that a combination of both medicines may lead to better outcomes, with the AE37 vaccine sensitizing cancer cells to Keytruda treatment.

“Increasing the number of patients with immune-activated tumors should bring the benefit of immunotherapy to even more patients,” said Liesha Emens, MD, PhD, professor at the University of Pittsburgh Medical Center and principal investigator of the new Phase 2 trial.