2132 - Pre-specified interim analysis of a randomized phase 2b trial of trastuzumab + nelipeptimut-S (NeuVax) vs trastuzumab for the prevention of recurrence demonstrates benefit in triple negative (HER2 low-expressing) breast cancer patients

Background

HER2 low-expressing (LE) (IHC 1-2+, non-amplified) breast cancer (BCa) patients (pts) are not eligible for HER2-targeted therapies as confirmed in the recent NSABP B-47 trial. We have shown the HER2-derived nelipeptimut-S (E75) + GM-CSF (NeuVax) is safe, immunogenic, & acts synergistically with trastuzumab (Tz) in pre-clinical & pilot clinical studies. Here, we present the interim analysis (IA) of a multi-center, prospective, randomized, single-blinded, placebo-controlled phase 2b trial of Tz + NeuVax vs Tz to reduce recurrence in HER2 LE, node positive (NP) and/or triple negative BCa (TNBC) pts.

Methods

Pts were randomized to receive Tz & NeuVax (vaccine group; VG) or Tz + GM-CSF (control group; CG). All pts received 1 year of Tz per label. NeuVax or GM-CSF was given Q3wk x 6 starting with 3rd Tz dose, then boosted Q6mo x 4. Cardiac ejection fraction (EF) was measured at baseline and serially on study. Pre-specified IA was triggered 6 mo after last enrollment. Analyses populations were intention-to- treat (ITT) & modified ITT/safety (mITT/S) (pts receiving ≥1 dose of NeuVax or GM-CSF). The primary endpoint is disease-free survival (DFS) at 24 mo evaluated by log-rank.

Results

275 pts were enrolled (VG n = 136, CG n = 139). No significant clinicopathologic differences were seen between groups. There was no difference between groups in related local (p = 0.19) or systemic (p = 0.85) toxicities (no grade 4/5 events) or in EF pre- to post-treatment (p = 0.60). At a median follow-up of 19.4 mo, estimated (est) 24 mo DFS in the VG vs CG was 88.6% vs 82.5% in ITT (p = 0.26, HR = 0.67) and 89.3% vs 82.3% in mITT/S (p = 0.17, HR = 0.61). In NP pts, est 24mo DFS in ITT VG vs CG was 85.9% vs 80.2% (p = 0.38, HR = 0.71), but in TNBC pts, it was 91.1% vs 69.9% (p = 0.02, HR = 0.26).

Conclusions

NeuVax + Tz is safe without added cardiac toxicity compared to Tz alone. The pre-specified IA shows efficacy trends overall in favor of the NeuVax + Tz combination, but most importantly demonstrates a highly significant clinical benefit in TNBC pts, suggesting the need for a definitive Ph3 study in this underserved pt population.

Clinical trial identification

NCT01570036.

Legal entity responsible for the study

George E. Peoples; Cancer Insight, LLC.

Funding

Sellas Life Sciences Group.

Editorial Acknowledgement

Disclosure

G.E. Peoples: NeuVax inventor rights. All other authors have declared no conflicts of interest.