- NeuVax™ (nelipepimut-S) Phase 2 VADIS trial design in women with ductal carcinoma in situ (DCIS)
- GALE-301 and GALE-302 Phase 1b clinical data in breast cancer patients
SAN RAMON, Calif., Dec. 12, 2016 (GLOBE NEWSWIRE) -- Galena Biopharma, Inc. (NASDAQ:GALE), a biopharmaceutical company committed to the development and commercialization of hematology and oncology therapeutics that address unmet medical needs, today announced that two posters were presented at the San Antonio Breast Cancer Symposium (SABCS).
Ductal Carcinoma in Situ (DCIS)
“The poster for NeuVax in patients with DCIS presents the Phase 2 clinical trial planned to assess the NeuVax effect in the most common type of non-invasive breast cancer in the U.S.,” said Bijan Nejadnik, M.D., Executive Vice President and Chief Medical Officer. “Despite high cure rates with the current standard of care treatments for DCIS, some patients still develop recurrences and may advance to breast cancer. The primary endpoint for the Phase 2 VADIS trial is immunologic, evaluating NeuVax-specific cytotoxic T-cells and whether long-lasting immunity is induced to suppress the growth of DCIS cells. We are appreciative of the efforts of Dr. Beth Mittendorf and her team, and the National Cancer Institute, as we look to advance NeuVax into this new and important indication.”
The poster, entitled, “VADIS trial: Phase 2 trial of the nelipepimut-S peptide vaccine in women with DCIS of the breast,” presented the trial design for the planned, Phase 2 investigator-sponsored clinical trial with NeuVax™ (nelipepimut-S) in patients with Ductal Carcinoma in Situ (DCIS). The trial is being conducted in collaboration with the National Cancer Institute (NCI) and The University of Texas MD Anderson Cancer Center Phase I and II Chemoprevention Consortium.
Little is known regarding the endogenous immune response to DCIS or the potential role of targeting DCIS with immunotherapy. This study was developed to test the NeuVax vaccine in women with DCIS to determine whether antigen-specific immunity is induced and whether the induced immune response suppresses the growth of DCIS cells. Completion of this study will determine the safety and immunologic efficacy of vaccination with NeuVax in patients with DCIS of the breast. The trial will also provide the necessary data to determine whether a subsequent, larger phase 2 or 3 trial will be conducted.
The primary endpoint will evaluate the effect of the NeuVax vaccine on NeuVax -specific cytotoxic T lymphocytes measured in the blood of patients with HLA-A2 positive DCIS. Secondary endpoints include evaluation of toxicity, In vivo immune response (delayed type hypersensitivity reaction (DTH)), epitope spreading, T-cell functional capacity, presence of DCIS at resection, and histologic immune response measured by degree of lymphocyte infiltration, proliferation, and apoptosis.
Elements of the inclusion criteria include pre- or post-menopausal women 18 years of age and older with a diagnosis of DCIS made by core needle biopsy and an area of radiographic abnormality measuring at least one centimeter. Trial participants must be HLA-A2 positive, have with an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Karnofsky ≥ 60%) and adequate kidney and liver function as measured by creatinine, bilirubin, and liver enzymes
The study design will operate as follows. Once the patient is identified, baseline testing and pre-study evaluation is done within thirty days prior to randomization. Patients are then randomized to either the NeuVax plus GM-CSF treatment arm (n=32 randomized/27 evaluable) or the GM-CSF only control arm (n=16 randomized/13 evaluable). Patients will receive three doses of the vaccine or control at Day 0, Day 14 ± 3 days, and Day 28 ± 3 days. Surgery to remove the DCIS is then performed at Day 35 ± 3 days and will include blood collection. DTH evaluations are done two to three days prior to and the day of the first dose. The post surgery clinical visit also includes DTH evaluation, cardiac evaluation, and blood collection. The final clinical visit with blood collection will take place 3 months ± 7 days post operation.
The poster presentation from the conference will be available on Galena’s website here. Additional details including clinical trial locations can be found on the ClinicalTrials.gov site here. The abstract can be found on the conference website here.
GALE-301 / GALE-302
The poster, entitled, “Determining the optimal vaccination strategy using a combination of the folate binding protein (FBP) peptide vaccine (E39+GM-CSF) and an attenuated version (E39') to maximize the immunologic response in breast cancer patients,” was presented on the breast cancer patients in the Company’s GALE-301 (E39) and GALE-302 (E39’) Phase 1b clinical trial targeting Folate Binding Protein.
Dr. Bejadnik continued, “Due to lower folate binding protein expression and less aggressive chemotherapy regimens, breast cancer patients are more antigen naïve and have a less suppressed immune system, which may support the use of an attenuated version of the vaccine in these patients, as presented in the poster. We continue to evaluate this program in both breast and ovarian cancer patients as we determine the best path forward for the assets.”
In the trial, both the E39 and E39’ peptide vaccines were noted to be well tolerated and immunogenic with no clinicopathologic differences between groups. Local reaction increased in all groups with administration of the vaccine as measured and assessed using orthogonal means. The greatest increase was seen in the treatment arm that administered GALE-301 followed by GALE-302, which approached statistical significance, and this arm was also the only arm with a statistically significant increase in DTH.
While no difference was seen in E39-specific CTLs between groups, the in vivo response was enhanced with the use of E39’ after E39. This may indicate expansion of more effective clonal populations of CD8+ T cells with this strategy. These results may be specific to breast cancer patients who are relatively antigen-naïve with intact immune systems. Further analysis of these patients as this trial continues will determine the optimal vaccination strategy capable of stimulating and maintaining effective immunity to prevent breast cancer recurrence.
Thirty-five HLA-A2-positive breast cancer patients were enrolled after completion of standard of care and without evidence of disease, with n=27 completing the primary vaccination series (PVS). The PVS includes six inoculations, one every 3-4 weeks containing 250mcg GM-CSF plus 500mcg peptide in the first five patients per arm and 250mcg GM-CSF + 1000mcg of peptide in the second five patients. To assess the in vivo immune response, local reaction was measured 48 hours after each inoculation, and delayed type hypersensitivity (DTH) was measured pre-PVS, and at one and six months post-PVS.
- E39 (GALE-301) x 6 inoculations (n=10)
- E39 (GALE-301) x 3 inoculations followed by E39’ (GALE-302) x 3 inoculations (n=8)
- E39’ (GALE-302) x 3 inoculations followed by E39 (GALE-301) x 3 inoculations (n=9)
The poster presentation from the conference will be available on Galena’s website here. The abstract can be found on the conference website here.
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). Phase 2 clinical trials with NeuVax are also planned in patients with ductal carcinoma in situ (DCIS), and in patients with gastric cancer.
About Ductal Carcinoma in Situ
Ductal Carcinoma in Situ (DUK-tul KAR-sih-NOH-muh in SY-too), or DCIS, is defined by the NCI as a noninvasive condition in which abnormal cells are found in the lining of a breast duct, and is the most common type of breast cancer. The abnormal cells have not spread outside the duct to other tissues in the breast. In some cases, DCIS may become invasive cancer and spread to other tissues; currently there is no way to know which lesions could become invasive. Current treatment options for DCIS include breast-conserving surgery and radiation therapy with or without tamoxifen, breast-conserving surgery without radiation therapy, or total mastectomy with or without tamoxifen. According to the American Cancer Society, in 2015 there were over 60,000 diagnoses of ductal carcinoma in situ.
About GALE-301 and GALE-302
GALE-301 and GALE-302 are cancer immunotherapies that consist of a peptide derived from Folate Binding Protein (FBP) combined with the immune adjuvant, granulocyte macrophage-colony stimulating factor (GM-CSF) for the prevention of cancer recurrence in the adjuvant setting. GALE-301 is the E39 peptide, while GALE-302 is an attenuated version of this peptide, known as E39’. FBP is a well-validated therapeutic target that is highly over-expressed in ovarian, endometrial and breast cancers, and is the source of immunogenic peptides that can stimulate cytotoxic T lymphocytes (CTLs) to recognize and destroy FBP-expressing cancer cells. Two trials are ongoing with FBP peptides: the GALE-301 Phase 2a portion of the Phase 1/2a clinical trial is ongoing in ovarian and endometrial adenocarcinomas (ClinicalTrials.gov Identifier: NCT01580696); the GALE-301 plus GALE-302 Phase 1b clinical trial is ongoing in breast and ovarian cancers (ClinicalTrials.gov Identifier: NCT02019524).
About Breast Cancer1
New cases of breast cancer occur at an annual rate of 125 per 100,000 women in the U.S., with an estimated 246,660 new cases and 40,450 deaths in 2016. Approximately 89.7% of breast cancer patients are expected to survive five years after diagnosis. Approximately 12.4% of women will be diagnosed with breast cancer at some point during their lifetime (2011 – 2013 data). The prevalence data from 2013 showed an estimated 3,053,450 women living with breast cancer in the United States.
1National Cancer Institute Surveillance, Epidemiology, and End Results Program
About Galena Biopharma
Galena Biopharma, Inc. is a biopharmaceutical company committed to the development and commercialization of hematology and oncology therapeutics that address unmet medical needs. Galena’s pipeline consists of multiple mid-to-late-stage clinical assets led by its hematology asset, GALE-401, and novel cancer immunotherapy programs including NeuVax™ (nelipepimut-S) and GALE-301/GALE-302. For more information, visit www.galenabiopharma.com.
Forward-Looking Statements
This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. Such statements include, but are not limited to, statements about the progress of the development of Galena’s product candidates, patient enrollment in our clinical trials, as well as other statements related to the progress and timing of our development activities, present or future licensing, collaborative or financing arrangements, expected outcomes with regulatory agencies, and projected market opportunities for product candidates or that otherwise relate to future periods. These forward-looking statements are subject to a number of risks, uncertainties and assumptions, including those identified under “Risk Factors” in Galena’s Annual Report on Form 10-K for the year ended December 31, 2015 and most recent Quarterly Reports on Form 10-Q filed with the SEC. Actual results may differ materially from those contemplated by these forward-looking statements. Galena does not undertake to update any of these forward-looking statements to reflect a change in its views or events or circumstances that occur after the date of this press release.
NeuVax is a trademark of Galena Biopharma, Inc.
Source: Galena Biopharma, Inc.