Long-term treatment with a combination of NeuVax (nelipepimut-S) and Herceptin (trastuzumab) is safe and extends the time without disease resurgence in women with triple-negative breast cancer, according to final results of a Phase 2b trial.
NeuVax, developed by Sellas Life Sciences, is an investigational cancer vaccine that contains small pieces derived from human epidermal growth factor receptor 2 (HER2), a protein found in many breast cancer cells. Once injected into the patient, NeuVax “teaches” the immune system to recognize and mount a response against HER2, ultimately killing cancer cells.
The randomized, controlled Phase 2b study (NCT01570036) assessed the efficacy and safety of the treatment combination in patients with low levels of HER2, including people with triple-negative breast cancer (TNBC), which refers to the lack of HER2, estrogen receptors, and progesterone receptors. All participants were disease-free after standard therapy.
A total of 275 patients were included; 136 received both NeuVax and Genentech’s Herceptin and 139 received Herceptin alone. NeuVax was given intradermally (within the skin) every three weeks for a total of six vaccinations. Herceptin was administered every three weeks for one year.
All patients were also given Leukine (sargramostim or GM-CSF, by Partner Therapeutics), to boost the number of immune cells and increase the anti-tumor activity of the vaccine.
Over a median follow-up of 25.7 months, more patients receiving the combination remained disease-free (89.8%), compared to those receiving Herceptin alone (83.8%), though the difference was not statistically significant.
However, in line with results from a preliminary analysis, the combination was significantly better in the subset of 97 patients with TNBC. At the time of the analysis, 92.6% of those on NeuVax plus Herceptin were free of cancer, compared to 70.2% of those on Herceptin only. This represented a 71.9% reduction in the frequency of clinically detected recurrences among patients receiving the combination.
As for safety, the groups showed no significant differences in mild to severe adverse events. No life-threatening adverse events or deaths occurred during the trial.
The two groups also did not differ in cardiac ejection fraction — how much blood the ventricles pump out each time they contract — at baseline and throughout the study.
The findings, “Final analysis of Nelipepimut-S plus GM-CSF with trastuzumab versus trastuzumab alone to prevent recurrences in high-risk, HER2 low-expressing breast cancer: A prospective, randomized, blinded, multicenter phase IIb trial,” were presented at the recent 2019 ASCO-SITC Clinical Immuno-Oncology Symposium in San Francisco.
“This final analysis of the study database establishes a clinically meaningful and statistically significant prolongation in [disease-free survival], a validated surrogate marker of overall survival for TNBC … and a meaningful decrease in the frequency of relapses identified by standard clinical follow-up in favor of [NeuVax] plus trastuzumab,” Elizabeth A. Mittendorf, MD, PhD, the trial’s principal investigator, said in a press release.
Mittendorf is the director of research of Breast Surgical Oncology at Brigham and Women’s Hospital, and director of the Breast Immuno-Oncology Program at the Dana-Farber/Brigham and Women’s Cancer Center.
“These findings could position the [NeuVax plus Herceptin] combination as an adjuvant therapy for early-stage TNBC and warrant further study,“ the researchers stated.
Nicholas J. Sarlis, MD, PhD, Sellas’ executive vice president and chief medical officer, said the positive efficacy results were “essentially confined to TNBC patients, and continue to encourage us and support our ongoing discussions with the U.S. Food and Drug Administration on the most appropriate registration-enabling development path for [NeuVax plus Herceptin] in TNBC.”
This combination is also being assessed as maintenance treatment for HER2-positive breast cancer at high risk of recurrence in a Phase 2 study (NCT02297698) with 100 patients.