Acute Myeloid Leukemia (AML)
In a Phase 2 trial in AML patients, in first complete remission, galinpepimut-S was shown to improve OS and PFS in comparison to historical data.
According to the Phase 2 trial results, administration of galinpepimut-S resulted in a median OS of 67.6 months, which represents a substantial improvement compared to best standard therapies. Serial active immunization with galinpepimut-S showed a well-tolerated safety profile in this patient population, whose median age was 63 years old. In addition, galinpepimut-S elicited immune responses in patients, including CD4+ and CD8+ T cell responses. The results also evidenced a trend in improved clinical outcomes in patients who mounted an immune response with galinpepimut-S compared to those patients who did not. A Phase 3 program for AML patients is currently being scheduled, pending funding availability.
Malignant Pleural Mesothelioma (MPM)
SELLAS randomized, double-blind, placebo-controlled Phase 2 study in MPM patients enrolled a total of 41 patients at MSKCC and M.D. Anderson Cancer Center.
According to an initial analysis of the Phase 2 MPM study data of galinpepimut-S presented at the 2016 International Mesothelioma Interest Group and the 2016 Annual Meeting of the American Society of Clinical Oncology, as of May 2016,and with a median follow-up of16.3 months, median OS of 24.8 months was recorded for galinpepimut-S-treated MPM patients, compared to a median 16.6 months OS for patients in the control arm. In that analysis, patients with a complete tumor resection and subsequent treatment with galinpepimut-S showed a significant survival benefit. In a subsequent analysis, and with a median follow up of17.2 months, median OS of 22.8 months was observed for galinpepimut-S-treated MPM patients, compared to a median 18.3 months OS for patients in the control arm (Zauderer M, et al, Clin Cancer Res, 2017). In the datasets from both these analyses, galinpepimut-S induced CD8+ and CD4+ T cell activation. Galinpepimut-S also demonstrated a well-tolerated safety profile in MPM patients. A Phase 3 clinical study in MPM is currently being scheduled, pending funding availability.
Multiple Myeloma (MM)
SELLAS has reported updated positive Phase 2 data from its WT1 immunotherapeutic anti-cancer treatment, galinpepimut-S, which indicate a meaningful clinical benefit among high-risk multiple myeloma (MM) patients.
High-risk MM patients typically relapse within 12 months after frontline induction therapy, followed by successful ASCT, even when they receive maintenance therapy with IMIDs. SELLAS reported updated positive Phase 2 data showing 88% actuarial OS at the 18-month landmark in 18 evaluable patients. All patients had evidence of MRD after ASCT and 15 had high-risk cytogenetics at diagnosis. Combined, these characteristics typically result in low PFS rates that do not exceed 12 months following ASCT, even while on maintenance therapy with IMIDs or proteasome inhibitors. Current median PFS is 23.6 months, while median OS has not been reached. SELLAS’ results compare favorably with an unmatched cohort of MM patients with high-risk cytogenetics published by the UK Medical Research Council (Myeloma IX trial). SELLAS’ galinpepimut-S therapy demonstrated a 2.5-fold increase in median PFS, as well as a 2.6-fold increase in the PFS rate at 18 months versus the aforementioned historical cohort, which included MM patients with high-risk cytogenetics and MRD post-ASCT and on continuous thalidomide maintenance. SELLAS’ Phase 2 study started in June 2014 and has enrolled a total of 20 patients, who are being monitored long-term. All non-progression events are confirmed and ongoing (median follow-up at 18 months for survivors).
Ovarian Cancer
SELLAS has an open-label, non-randomized Phase 1/2 clinical study underway to evaluate the safety and efficacy of galinpepimut-S in combination with nivolumab (Opdivo®), a PD-1 immune checkpoint inhibitor, in patients with recurrent ovarian, fallopian tube or primary peritoneal cancer who are in second or greater clinical remission.
This Phase 1/2 study is expected to enroll at least ten patients with recurrent ovarian cancer who are in second or greater clinical remission at MSKCC. Patients enrolled in the study will receive the combination therapy during the study’s 14-week treatment period. Individuals who have not progressed by the end of this period will also receive a maintenance course of the galinpepimut-S. Pending the successful progress of this study a larger, follow-on, randomized study may be planned. Initial data are due soon, with a primary endpoint being to assess the safety of repeated vaccination with galinpepimut-S for a total of 6 vaccinations in combination with 7 infusions of nivolumab.
Hematology And Solid Tumors
Galinpepimut-S and KEYTRUDA® (pembrolizumab) combination trial (5 indications)
In October 2017, SELLAS entered into a Clinical Trial Collaboration and Supply Agreement for the conduct of a combination clinical trial targeting multiple cancer types with Merck & Co., Inc., Kenilworth, N.J., USA (known as MSD outside the United States and Canada). SELLAS' Wilms tumor-1 (WT1)-targeting peptide immunotherapeutic agent, galinpepimut-S, will be administered in combination with MSD's anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in a Phase 1/2 trial enrolling patients in five cancer indications, including both hematologic malignancies and solid tumors. The Phase 1/2 trial will utilize a combination of galinpepimut-S plus KEYTRUDA in patients with WT1-positive relapsed or refractory tumors. Specifically, the study is expected to explore the following cancer indications: colorectal (arm enriched in but not exclusive to patients with microsatellite instability-low [MSI-L]), ovarian, small cell lung, triple-negative breast, and AML. This study will assess the efficacy and safety of the combination, comparing overall response rates (ORRs) and immune response markers achieved with the combination versus prespecified rates based on those seen with KEYTRUDA alone in comparable patient populations. The trial is anticipated to begin in the first half of 2018.
Breast Cancer - NeuVaxTM (Nelipepimut-S)
SELLAS is supporting an ongoing investigator-sponsored trial (IST) with NeuVax in combination with trastuzumab (Herceptin®; Genentech/Roche) in HER2 1+/2+ breast cancer patients.
The Phase 2b clinical trial is a randomized, multicenter, investigator-sponsored, 300 patient 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. The interim analysis is expected in Q1, 2018 and the primary endpoint of disease-free survival is expected to be reached in Q4, 2019. This IST is a clinical collaboration between SELLAS, Genentech/Roche, and the Henry M. Jackson Foundation.
SELLAS is supporting an ongoing IST with NeuVax in combination with trastuzumab (Herceptin®; Genentech/Roche) in HER2 3+ patients.
This multi-center, prospective, randomized, single-blinded Phase 2 trial is enrolling approximately 100 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 those who undergo surgery as a first intervention and are found to be pathologically node-positive. Eligible patients will be randomized to receive NeuVax + GM-CSF plus trastuzumab or GM-CSF plus trastuzumab alone. The primary endpoint of the study is disease-free survival and is expected to be reached in Q4, 2019. Funding for this trial was awarded through the Congressionally Directed Medical Research Program (CDMRP), funded through the Department of Defense (DoD), via a Breast Cancer Research Program (BCRP) Breakthrough Award.
SELLAS is supporting an ongoing IST with NeuVax in patients with Ductal Carcinoma in Situ (DCIS), entitled: VADIS: Phase 2 trial of the Nelipepimut-S Peptide VAccine in Women with DCIS of the Breast.
VADIS is a Phase 2 trial to evaluate women diagnosed with DCIS who are HLA-A2 positive, who express HER2 at IHC 1+, 2+, or 3+ levels, and who are pre or post menopausal. Patients will be randomized to one of two arms: NeuVax plus GM-CSF or GM-CSF alone. The primary endpoint is immunologic and will evaluate the effect of the NeuVax vaccine on NeuVax -specific cytotoxic T lymphocytes to determine whether long-lasting immunity is induced. DCIS is a noninvasive cancer in which abnormal cells are found in the lining of the breast duct and have not spread outside the milk duct to invade other parts of the breast. DCIS is the most common type of breast cancer, and in some cases, DCIS may become invasive cancer and spread to other tissues; currently it is extremely challenging to identify which lesions may convert to invasive cancer. This trial is being run in collaboration with the National Cancer Institute (NCI) Division of Cancer Prevention. The University of Texas-M.D. Anderson Cancer Center (MDACC) Phase I and II Chemoprevention Consortium is the lead for this multi-center trial.
Essential Thrombocythemia - Anagrelide Controlled Release (CR)
Multiple Phase 1 studies in 98 healthy subjects have shown Anagrelide Controlled Release (CR) reduces the Cmax of anagrelide and increases the half-life following oral administration, appears to be well tolerated at the doses administered, and to be capable of reducing platelet levels effectively.
The Phase 1 program provided the desired PK/PD (pharmacokinetic/pharmacodynamic) profile to enable the initiation of the Phase 2 proof-of-concept trial. The Phase 2, open label, single arm, proof-of concept trial enrolled 18 patients in the United States for the treatment of thrombocytosis, or elevated platelet counts, in patients with MPNs and demonstrated a prolonged clinical benefit with a well-tolerated safety profile. GALE-401 contains the active ingredient anagrelide, an FDA-approved product, for the treatment of patients with myeloproliferative neoplasms (MPNs) to lower abnormally elevated platelet levels. The currently available immediate release (IR" version of anagrelide causes adverse events that are believed to be dose and plasma concentration dependent, and may limit the use of the IR version of the drug. Therefore, reducing the maximum concentration (Cmax) and increasing the half-life of the drug is hypothesized to reduce the side effects, while preserving the efficacy, potentially allowing a broader use of the drug. The work has been completed to initiate a registration-enabling clinical study with Anagrelide CR in patients with Essential Thrombocythemia ("ET") who are intolerant or resistant to hydroxyurea. The FDA has confirmed that the development program is appropriate for a New Drug Application (NDA) filing using the 505(b)(2) regulatory pathway.