Clinical Trials

Date: 2017-02-06

Type of information: DSMB assessment

phase: 2b

Announcement: DSMB assessment

Company: Galena Biopharma (USA - OR)

Product: NeuVax™ (nelipepimut-S) in combination with trastuzumab (Herceptin®)

Action mechanism:

• peptide/immunotherapy product. NeuVax™ (nelipepimut-S) is an immunodominant nonapeptide derived from the extracellular domain of the HER2 protein, which is expressed in ovarian and pancreatic cancers as well as in breast cancer. NeuVax™ has been shown to bind to HLA-A2 and A3, as well as HLA-A24 and A26 molecules. The nelipepimut-S sequence stimulates specific CD8+ cytotoxic T lymphocytes (CTLs) following binding to specific HLA molecules on antigen presenting cells (APC). These activated specific CTLs recognize, neutralize and destroy, through cell lysis, HER2 expressing cancer cells, including occult cancer cells and micrometastatic foci. The nelipepimut-S immune response can also generate CTLs to other immunogenic peptides through inter- and intra-antigenic epitope spreading leading to a broader, more robust anti-tumor immune response.

Disease: node positive and triple negative, node negative breast cancer patients with immunohistochemistry HER2 1+/2+ expressing tumors who are disease-free after standard of care therapy

Therapeutic area: Cancer - Oncology

Country:

Trial details:

• The clinical trial is a randomized, multicenter, investigator-sponsored, 300 patient Phase 2b study. It is currently enrolling HER2 1+ and 2+ node positive, and high-risk node negative patients to study NeuVax in combination with trastuzumab to prevent breast cancer recurrence. (NCT02297698)

Latest news:

• • On February 6, 2017,  Galena Biopharma announced the results from a meeting of the Data Safety Monitoring Board (DSMB) for the two investigator-sponsored (IST) combination clinical trials with NeuVax™ (nelipepimut-S) plus trastuzumab. The trials are being run in breast cancer patients to assess the ability of the combination of trastuzumab and the HER2 vaccine nelipepimut-S (administered with the immunoadjuvant granulocyte macrophage-colony stimulating factor) to prevent recurrence in the adjuvant setting. In light of the early termination of the NeuVax Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) trial last year, the independent DSMB performed separate futility assessments on each of the NeuVax plus trastuzumab combination trials. The DSMB reported that there are no safety concerns with either trial and neither was found to be futile. For the Phase 2b trial in patients with low-to-intermediate HER2 expression (HER2 1+/2+), n=242 patients were evaluated, and the recommendation from the DSMB is to continue the trial with one revision to the statistical analysis plan regarding the timing of the pre-specified interim analysis. Given the lengthy duration of enrollment for the trial, the DSMB determined that the pre-specified interim efficacy analysis be moved up from 12 months to 6 months after the last patient is enrolled. Completion of enrollment is expected in the second quarter of 2017; therefore, the DSMB expects to perform the interim efficacy analysis near the end of 2017. For the Phase 2 trial in high-risk, HER2 3+ patients, and per the trial protocol, the pre-specified interim safety analysis was also completed on n=50 patients and demonstrated that the agent is well tolerated with no increased cardiotoxicity associated with giving NeuVax in combination with trastuzumab. These findings were similar to the findings presented in October 2016 from the HER2 1+/2+ trial. The recommendation from the DSMB is to continue the HER2 3+ trial unmodified.
• • On October. 10, 2016, Galena Biopharma presented interim safety data from NeuVax™ (nelipepimut-S) Phase 2b combination study with trastuzumab at the European Society for Medical Oncology 2016 (ESMO 2016) Congress in Copenhagen, Denmark . Poster #1069P, entitled “Interim safety analysis of a phase II trial combining trastuzumab and NeuVax, a HER2-targeted peptide vaccine, to prevent breast cancer recurrence in HER2 low expression,” demonstrated that this novel combination of trastuzumab and NeuVax in HER2 low-expressing (LE) patients is well-tolerated and the cardiac effects of trastuzumab are not impacted by the addition of NeuVax. In March 2016 , the 150th patient was randomized into the trial, triggering this pre-specified safety analysis ( Vaccine Group (VG) n=81, Control Group (CG) n=69). There were no significant differences in treatment factors, but a significant difference in node positivity appreciated between the groups. The sponsor expects this randomization imbalance to equalize over the duration of the study. Cardiac ejection fraction (EF) was assessed at baseline and serially throughout treatment. The majority of toxicities were Grade 1 and 2, and there was no difference between treatment arms. There was no difference in EF over time (baseline (T0) to 6mo (T6)) between VG v CG (T0: 61.4+0.6%, T6: 60.5+0.9% v T0: 61.6+0.7%, T6: 60.7+1.0%, p=0.9). There was one CG patient who experienced a grade 3 cardiac adverse event, but their EF returned to baseline after discontinuation of trastuzumab. Disease-free, HLA-A2+, A3+, A24+, or A26+, HER2 LE breast cancer patients at high risk for recurrence were enrolled after standard of care treatment and randomized to vaccine group (VG) receiving trastuzumab and NeuVax or control group (CG) receiving trastuzumab and GM-CSF only. Trastuzumab dosing was 8mg/kg loading, then 6mg/kg every 3 weeks. Patients received 6 total inoculations of NeuVax or GM-CSF, one every 3 weeks starting with the third trastuzumab infusion, followed by four booster inoculations administered every 6 months. Demographic and safety data were collected and analyzed with appropriate statistical tests.
• • On March 26, 2015, Galena Biopharma announced that human leukocyte antigen (HLA) - A24+ or HLA-A26+ women are now eligible for enrollment into the ongoing Phase 2b clinical trial with NeuVax™ (nelipepimut-S) in combination with trastuzumab (Herceptin®). The trial evaluates node positive and triple negative, node negative breast cancer patients with immunohistochemistry (IHC) HER2 1+/2+ expressing tumors who are disease-free after standard of care therapy. The nelipepimut-S peptide works by binding to specific HLA proteins, or molecules key to immunological activity and are involved in the induction of protective T-cell immune responses. To date, NeuVax has been tested in trials with patients who are HLA-A2+ or A3+, representing more than 60% of the North American, European and Chinese populations. NeuVax has also been shown to bind to HLA-A24 and A26, which represents an additional 10-15% of the population in the U.S., but more importantly, represents up to approximately 70% of the population in Japan.

Is general: Yes