A pre-specified interim analysis, conducted by an independent Data Safety Monitoring Board (DSMB) of the efficacy and safety data for the study in an overall population of 275 patients as well as the two primary study target patient populations (node-positive and TNBC) after a median follow-up of 19 months, demonstrated a clinically meaningful difference in median disease-free survival (DFS) in favor of the active arm (NeuVax + Herceptin), a primary endpoint of the study, with hazard ratios of 0.67 and 0.61 in the intent to treat (ITT) and modified ITT (mITT) populations (i.e., those who received at least one dose of vaccine or control) as well as a 34.9% and 39.5% reduction in relative risk of recurrence in the active versus control arms in the ITT and mITT populations, respectively.
A clinically meaningful and also statistically significant difference was found between the two arms in the cohort of patients (n= 98) with triple-negative breast cancer (TNBC), with a hazard ratio of 0.26 and a p-value of 0.023 in favor of the NeuVax + Herceptin combination with a 70.4% reduction in relative risk of recurrence in the active arm versus control.
Similarly, a clinically meaningful and statistically significant difference was found between the two arms in favor of the combination in the cohort of patients not receiving hormonal therapy (n = 110), with a hazard ratio of 0.24 and a p-value of 0.009 with a 74.1% reduction in relative risk of recurrence in the active arm versus control.
This pre-specified interim analysis also showed an adverse event profile with no notable differences between treatment arms. The addition of NeuVax to Herceptin did not result in any additional cardiotoxicity compared to Herceptin alone.
Sellas president and CEO Angelos Stergiou said: “We are indeed excited about these compelling results and believe NeuVax + Herceptin has the potential to become an important therapeutic option for TNBC patients.
“The positive NeuVax phase 2b data underscores the innovative science and approach we have taken to investigate this agent’s potential to address this persistent therapeutic challenge.
“We plan to immediately engage with the FDA and EMA, as per the recommendation of the DSMB, to identify the optimal path forward in this particular patient group, while advancing the drug through a partnership or other strategic collaboration.”
The NeuVax + Herceptin combination was found to be generally well-tolerated. The majority of treatment-emergent adverse events (TEAE) were of mild or moderate (G1/G2) severity and the majority of G3 systemic TEAEs were unrelated to NeuVax. Treatment-related adverse events consisted primarily of manageable local injection site reactions, skin induration, pruritus and fatigue.
Additionally, in the NeuVax + Herceptin arm, in vivo HER2-specific T-cell immune responses (IRs), assessed by delayed type hypersensitivity (DTH) skin testing, showed a time-dependent increase in IR potency compared to the earliest tested datapoint (p=0.000023), while no such increase was observed in the control arm.
Based on the results above, the DSMB has recommended to expeditiously seek regulatory guidance by the FDA for further development of the combination of NeuVax + Herceptin in TNBC, considering the statistically significant benefit of the combination therapy seen in this population with large unmet medical need.
This Phase 2b trial is a multi-center, randomized, single-blinded, placebo-controlled trial in 275 HER2 1+/2+ breast cancer patients with positive nodes and/or TNBC. The study combines NeuVax and trastuzumab (Herceptin) in the adjuvant setting aiming to prevent recurrence or death.
Tumors in these women show low levels of expression of HER2, as measured by immunohistochemistry (IHC), i.e., at a level of either 1+ or 2+ and, hence, these patients are not considered candidates for Herceptin. Patients who are hormone receptor-negative and HER2 1+/2+ by IHC are currently defined as ‘triple-negative’ breast cancer (TNBC) patients.
NeuVax (nelipepimut-S) is a potentially first-in-class, HER2-directed cancer immunotherapy and is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma.
Source: Company Press Release