On September 28, 2017 Galena Biopharma, Inc. (NASDAQ: GALE), a biopharmaceutical company developing hematology and oncology therapeutics that address unmet medical needs, reported that two clinical trials evaluating NeuVax (nelipepimut-S) in combination with trastuzumab (Herceptin; Genentech/Roche) for the prevention of recurrence in breast cancer patients have enrolled the protocol-defined number of patients to complete enrollment (Press release, Galena Biopharma, SEP 28, 2017, View Source [SID1234520707]). The milestones were reported by the clinical research organization conducting both trials – a Phase 2b clinical trial in HER2 1+/2+ patients and a Phase 2 clinical trial in HER2 3+ patients.
“Completing enrollment in both of these trials represents a major milestone for NeuVax development,” said Bijan Nejadnik, M.D., Executive Vice President and Chief Medical Officer of Galena. “The combination of trastuzumab and NeuVax has been shown to be synergistic in preclinical investigation, and we believe could be an effective treatment to prevent breast cancer recurrence in patients with no other treatment options. We would like to thank our investigators and patients who are participating in these trials as we look forward to the interim results next year for the Phase 2b trial and the primary endpoints for both trials in 2019.”
Phase 2b Clinical Trial in HER2 1+/2+ Patients
The Phase 2b clinical trial has enrolled the necessary 300 patients to complete enrollment. The clinical trial is a randomized, multicenter, investigator-sponsored, study enrolling HER2 1+ and 2+, HLA A2+, A3+, A24 and/or A26, node positive, and high-risk node negative breast cancer patients. Eligible patients are randomized to receive NeuVax + GM-CSF + trastuzumab or trastuzumab + GM-CSF alone. Once enrolled, all patients receive the standard trastuzumab dosing for 12 months. One cohort also receives six doses of NeuVax given as a primary vaccine series starting with the third dose of trastuzumab and then goes on to receive a NeuVax booster inoculation once every six months for up to 36 months. The next milestone for the trial will be the interim efficacy analysis that is scheduled to be performed by the Data Safety Monitoring Board (DSMB) in the first quarter of 2018. The primary endpoint of the study is disease-free survival after 24 months, with results expected from that milestone in the fourth quarter of 2019. Genentech/Roche is providing the trastuzumab and partial funding for this trial.
Data presented in October 2016 demonstrated that this novel combination of trastuzumab and NeuVax with HER2 low-expressing patients is well tolerated and the cardiac effects of trastuzumab are not impacted by the addition of NeuVax. In February 2017, the DSMB reported that there were no safety concerns with the trial and the trial is not futile. The recommendation from the DSMB was 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. Therefore, the DSMB expects to perform the interim efficacy analysis in the first quarter of 2018.
Phase 2 Clinical Trial in HER2 3+ Patients
The Phase 2 clinical trial has enrolled the necessary 100 patients to complete enrollment. This multi-center, prospective, randomized, single-blinded trial enrolled patients with a diagnosis of HER2 3+ breast cancer who are HLA A2+ or HLA A3+ and are determined to be at high-risk for recurrence. High-risk is defined as having received neoadjuvant therapy with an approved regimen that includes trastuzumab but not obtaining a pathological complete response at surgery, or underwent surgery as a first intervention and was found to be pathologically node-positive (³4 positive lymph nodes, or having 1-3 positive lymph nodes (pN1) if hormone receptor negative). These high-risk patients are known to have higher recurrence rates than other HER2 3+ breast cancer patients. Eligible patients are randomized to receive NeuVax + GM-CSF + trastuzumab or trastuzumab + GM-CSF alone. Once enrolled, all patients receive the standard trastuzumab dosing for 12 months. One cohort also receives six doses of NeuVax given as a primary vaccine series starting with the third dose of trastuzumab and then goes on to receive a NeuVax booster inoculation once every six months for up to 36 months. The primary endpoint of the study is disease-free survival after 24 months, with results expected from that milestone in the fourth quarter of 2019. Partial funding for this trial was awarded through the Congressionally Directed Medical Research Program funded through the Department of Defense, via a Breast Cancer Research Program Breakthrough Award.
In February 2017, the DSMB reported that there were no safety concerns with the trial and the trial is not futile. The pre-specified interim safety analysis was 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. The recommendation from the DSMB was to continue the HER2 3+ trial unmodified.
About NeuVax (nelipepimut-S)
NeuVax (nelipepimut-S) is a first-in-class, HER2-directed cancer immunotherapy under evaluation to prevent breast cancer recurrence after standard of care treatment in the adjuvant setting. It is the immunodominant peptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. 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. In clinical studies, NeuVax is combined with recombinant granulocyte macrophage-colony stimulating factor (GM-CSF).
NeuVax is currently in two breast cancer studies in combination with trastuzumab (Herceptin; Genentech/Roche): a Phase 2b trial in node positive and triple negative HER2 IHC 1+/2+ (clinicaltrials.gov identifier: NCT01570036); and, a Phase 2 trial in high risk, node positive or negative HER2 IHC 3+ patients (clinicaltrials.gov identifier: NCT02297698). A Phase 2 clinical trial is also ongoing with NeuVax in patients with ductal carcinoma in situ (DCIS) (clinicaltrials.gov identifier: NCT02636582), and a Phase 2 trial is planned in patients with gastric cancer.