Clinical Trials

Date: 2017-09-28

Type of information: Completion of patient enrollment

phase: 3

Announcement: completion of patient enrollment

Company: Galena Biopharma (USA - OR)

Product: NeuVax™ (nelipepimut-S)

Action mechanism:

• peptide/immunotherapy product. NeuVax™ (nelipepimut-S) is an immunodominant nonapeptide derived from the extracellular domain of the HER2 protein, a well-established target for therapeutic intervention in breast carcinoma. 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 breast cancer

Therapeutic area: Cancer - Oncology

Country: Bulgaria, Canada, Czech Republic, France, Germany, Hungary, Israel, Poland, Romania, Russian Federation, Ukraine, UK, USA

Trial details:

• PRESENT is a randomized, double blind, placebo controlled, international, Phase 3 trial and the leading study in Galena's pipeline. The trial is currently running in 13 countries at more than 140 sites. The PRESENT trial targets the approximately 50%-60% of women with breast cancer who are low to intermediate (immunohistochemistry [IHC] 1+/2+ or fluorescence in situ hybridization [FISH] < 2.0) HER2 expression and achieved no evidence of disease with current standard of care treatment (surgery, chemotherapy, and radiation therapy). Patients must be lymph node positive, haplotype (HLA) A2 or A3 positive, and have Stage IIa-IIIa breast cancer. Once patients have completed their current standard of care treatment, with no available HER2-targeted adjuvant treatment options to maintain their disease-free status, patients are administered an injection once a month for six months (Primary Vaccine Series), then receive five booster injections once every six months for a total of eleven injections over a three year period. The final endpoint is currently expected to be reached in 2018, after the last patient dosed reaches her 36th month of treatment, or 141 events (recurrence or death), whichever comes later. (NCT01479244)
• Galena has two additional breast cancer studies ongoing with NeuVax™ in combination with trastuzumab (Herceptin®; Genentech/Roche): a Phase 2b trial in node positive and high risk node negative HER2 IHC 1+/2+ (NCT01570036); and, a Phase 2 trial in neoadjuvantly treated node positive and negative HER2 IHC 3+ patients not achieving a pathological complete response (pCR) or adjuvantly treated node positive HER2 IHC 3+ patients (NCT02297698).

Latest news:

• • On September 28, 2017, Galena Biopharma announced that two clinical trials evaluating NeuVax™ (nelipepimut-S) in combination with trastuzumab for the prevention of recurrence in breast cancer patients have enrolled the protocol-defined number of patients to complete enrollment. 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. The company is now looking forward to the interim results next year for the Phase 2b trial and the primary endpoints for both trials in 2019.
• 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 de?ned 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 (? 4 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.
• • On June 29, 2016, Galena Biopharma announced the recommendation from the Independent Data Monitoring Committee (IDMC) on the interim analysis for Galena’s NeuVax™ (nelipepimut-S) Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) clinical trial. On June 27, 2016 , the IDMC recommended that the PRESENT trial be stopped due to futility. This planned safety and futility interim analysis was triggered after 70 qualifying disease free survival (DFS) events were reached, and a total of 71 events were reviewed by the IDMC.
• • On March 29, 2016, Galena Biopharma announced that the 70th qualifying disease free survival (DFS) event has been achieved in the NeuVax™ (nelipepimut-S) Phase 3, PRESENT (Prevention of Recurrence in Early-Stage, Node Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) clinical trial. Based on clinical and radiological data, seventy qualifying DFS events have been confirmed by the trial’s independent Endpoint Adjudication Committee (EAC), comprised of two oncologists and one radiologist with expertise in the conduct of clinical trials in breast cancer. In the ensuing months, Galena will compile and submit the clinical data to the trial’s Independent Data Monitoring Committee (IDMC) to perform the Interim Analysis. The Interim Analysis is a pre-specified futility and overall safety analysis to evaluate the likelihood of the study to achieve its primary objectives. Upon completion of this prospective analysis, the IDMC will provide a recommendation to the Company regarding further continuation of the trial. For the PRESENT trial, a qualifying DFS event is defined as: a recurrence of the primary breast cancer, either locally in the breast, regionally in the lymph nodes, or distantly as metastatic disease; an occurrence of another cancer; or, death from any cause. All qualifying DFS events are confirmed by the EAC. The IDMC is comprised of two medical oncologists, one cardiologist, and one statistician and will perform the Interim Analysis.
• • On August 24, 2015, Galena Biopharma announced that the Independent Data Monitoring Committee (IDMC) has recommended to the Company that it can reduce the cardiac toxicity monitoring for patients in its NeuVax™ (nelipepimut-S) Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVaxTreatment) clinical trial. Following its most recent IDMC meeting in June 2015, the IDMC recommended routine cardiac monitoring could be reduced in the PRESENT trial and that such a reduction is justified and consistent with the pre-specified Cardiac Toxicity Monitoring Stopping Rules defined in the study protocol. The IDMC concluded that cardiac toxicity monitoring by echocardiogram (ECHO) or multiple-gated acquisition (MUGA) scans could be reduced. The IDMC had no other suggestions and recommended the trial continue as planned.
• • On May 27, 2015, Galena Biopharma announced  an abstract publications at the American Society of Clinical Oncology (ASCO) 2015 Annual Meeting. As part of the Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVax Treatment) trial, Galena implemented central laboratory testing for all potential patients to confirm validated and robust entry criteria, and to ensure the enrollment of the targeted patient population. To improve accuracy and specificity for the HER2 1+ and 2+ status testing, and develop a companion diagnostic for NeuVax, the Leica Bond Oracle™ HER2 Immunohistochemistry (IHC) system has been incorporated as central HER2 screening for the PRESENT study. In abstract #e11609, entitled, "Analytical Validation of BOND Oracle HER2 IHC System for Identifying Low to Intermediate HER2 Expressing Breast Cancer in NeuVax PRESENT Phase 3 Clinical Trial," data demonstrate a direct correlation between cell line receptor load, quantitative measure of HER2 protein, and IHC score. The ability to discriminate HER2 protein expression at the low and intermediate levels in breast cancer tumors will identify patients for new treatments in development such as NeuVax. Specifically, the validation of the Bond Oracle HER2 IHC System to distinguish lower levels of HER2+ expressions supports its use as a companion diagnostic.
• • On April 14, 2015, Galena Biopharma announced the completion of enrollment in the NeuVax™ (nelipepimut-S) Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVaxTreatment) clinical trial. NeuVax™ 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. As anticipated, Galena over-enrolled the trial by 7.7% with a total of 758 patients now in the intent-to-treat (ITT) population. The protocol for the PRESENT trial, being conducted under an FDA approved Special Protocol Assessment (SPA), called for 700 patients; and, the Company expects this higher number of ITT patients will increase the confidence in both the timing and quality of the statistics and the final outcome of the trial. The primary endpoint is currently expected to be reached in 2018, after the last patient dosed reaches her 36th month of treatment, or a total of 141 events (recurrence or death) occur, whichever comes later.
• • On February 9, 2015, Galena Biopharma, a biopharmaceutical company developing and commercializing innovative, targeted oncology treatments that address major medical needs across the full spectrum of cancer care, announced enrollment of the 700th patient in the NeuVax™ (nelipepimut-S) Phase 3 PRESENT (Prevention of Recurrence in Early-Stage, Node-Positive Breast Cancer with Low to Intermediate HER2 Expression with NeuVaxTreatment) clinical trial. Seven hundred is the patient enrollment target as defined by the PRESENT Phase 3 clinical trial protocol. A Special Protocol Assessment (SPA) was granted by the FDA on the PRESENT trial, certifying the agreement with the FDA regarding the study endpoints, study design and statistical assumptions of the clinical trial. As previously mentioned by the Company, Galena is continuing to enroll those identified patients who are completing their standard of care and have passed their initial qualifications for potential enrollment in the trial. The Company expects over-enrollment will increase the confidence in both the timing and quality of the statistics and the final outcome of the trial. Completion of final enrollment in the trial is expected near the end of the first quarter of 2015.

 

Is general: Yes