Date: 2016-11-14
Type of information: Presentation of results at a congress
phase: 1-2
Announcement: presentation of results at the Society for Immunotherapy of Cancer Conference 2016 in National Harbor , Maryland
Company: Galena Biopharma (USA - OR)
Product: GALE-301 GALE-302 (Folate Binding Protein (FBP))
Action
mechanism: peptide/immunotherapy product. 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.
Disease: breast cancer, ovarian cancer
Therapeutic area: Cancer - Oncology
Country: USA
Trial
details: This is a single-center, randomized, single-blinded, three-arm phase Ib study of the folate binding protein vaccines E39 and J65. The study target population are patients with breast or ovarian cancer diagnosis who have been treated and are without evidence of disease. Disease-free subjects after standard of care multi-modality therapy will be screened and HLA typed. E39 and J65 are cytotoxic T-lymphocyte-eliciting peptide vaccines that are restricted to HLA-A2+ patients (approximately 50% of the U.S. population). (NCT02019524)
Latest
news: * On November 14, 2016, Galena Biopharma announced that data from GALE-301/GALE-302 clinical program was presented at the Society for Immunotherapy of Cancer Conference 2016. The Phase 1b is a single-center, randomized, single-blinded, three-arm study in patients with breast or ovarian cancer diagnosis who were treated with standard of care and showed no evidence of disease at enrollment. This trial augments the Phase 1/2a trial with single-agent GALE-301 in ovarian and endometrial cancers.
Previous trials have demonstrated that although boosting vaccinations help to maintain long-lasting immunity, attenuated peptides may be a better choice for boosting because over-stimulation with an immunogenic peptide may lead to cytotoxic T lymphocyte (CTL) exhaustion and death. This phenomenon is known as antigen-induced cell death. The presentation, entitled, “Phase Ib Trial of Two Folate Binding Protein (FBP) Peptide Booster Vaccines (E39 and E39') in Breast and Ovarian Cancer Patients,” reported the peptide-specific immune response to E39 and E39' after different combinations of vaccination and boosting.
Both E39 and E39' are well tolerated with all related adverse events at grade 1 or grade 2. Though numbers were small, patients boosted with the attenuated peptide showed increased CTL response to boosting regardless of significant residual immunity (SRI) resulting from the primary vaccination series (PVS). While this data needs to be confirmed with a larger sample size, this is consistent with the theoretical advantage of boosting with an attenuated peptide, which is expected to induce less antigen-induced cell death of CTLs.
Ex-vivo immunologic recognition of E39 was assessed by clonal expansion of CTLs and in-vivo response by delayed-type hypersensitivity (DTH). Immunologic data was gathered at 1- and 6-months post-booster and was then analyzed. The 6-month post-PVS immunologic data was used to assess patients for SRI, defined as ?2-fold increase from pre-PVS in E39-specific CD8+T-cells. Patients were sorted into two groups: those with SRI (SRI) and without (nSRI). Patients within each group were randomized to one booster of either E39’ or E39 resulting in four groups:
SRI receiving E39 (SRI-E39)
SRI receiving E39' (SRI-E39')
nSRI receiving E39 (nSRI-E39)
nSRI receiving E39' (nSRI-E39')
Sixteen patients were found to have SRI and 12 had nSRI; these patients were randomized to booster arms (SRI-E39:n=9; SRI-E39':n=7; nSRI-E39:n=7; nSRI-E39':n=5). There were no clinicopathologic differences between groups. When comparing DTH pre-booster and at 1- and 6- months post-booster there were no significant differences between SRI vs nSRI (p=0.350, p=0.276, p=0.133, respectively), E39 vs. E39' (p=0.270, p=0.329, p=0.228), nor between all four groups (p=0.394, p=0.555, p=0.191). Comparing the change in CTL’s from pre- and 6-months post-booster, regardless of SRI, patients boosted with E39’ had increased CTL (+0.02) while those boosted with E39 had decreased CTL (-0.07, p=0.077). There was no difference comparing the change in DTH between groups (p=0.927).
HLA-A2-positive breast or ovarian cancer patients were enrolled after completion of standard of care and without evidence of disease, regardless of FBP expression level. The PVS includes six inoculations, one every 3-4 weeks containing 250mcg GM-CSF plus 500mcg peptide in the first five patients per arm (n=14) and 250mcg GM-CSF + 1000mcg of peptide in the second five patients (n=16). Thirty-nine patients were randomized into three arms with 30 breast (n=27) or ovarian (n=3) cancer patients completing the PVS and assessed for this presentation:
E39 (GALE-301) x 6 inoculations (n=10)
E39 (GALE-301) x 3 inoculations followed by E39’ (GALE-302) x 3 inoculations (n=10)
E39’ (GALE-302) x 3 inoculations followed by E39 (GALE-301) x 3 inoculations (n=10)
