Sellas reversed merged into Galena, a peptide vaccine company whose lead product, NeuVax, for breast cancer failed. Sellas’ lead product is galinpepimut-S for AML (acute myelogenous leukemia) and mesothelioma, as well as other cancers.
What is WT1 (Wilms Tumor Protein)?
WT1 is a cancer antigen is a transcription factor that contains four zinc-finger motifs at the C-terminus and a proline/glutamine-rich DNA-binding domain at the N-terminus. It has an essential role in the normal development of the urogenital system, and it is mutated in a small subset of patients with Wilms tumor (the most common cancer in children). It is involved in cell proliferation, differentiation, as well as apoptosis and organ development. It is over-expressed in many solid and hematological malignancies.
The National Cancer Institute found WT1 to be the highest priority tumor antigen suitable for multi-cancer vaccine development based on based on specificity, oncogenicity, immunogenicity and therapeutic function.
What is galinpepimut-S?
Sellas is developing galinpepimut-S, which is a vaccine consisting of comprised of four WT1 modified heteroclitic peptide chains, two of which are modified chains that induce a strong immune response (CD4+/CD8+) against the WT1 antigen and are expressed on a broad range of HLA types. The peptides were discovered at Memorial Sloan Kettering. It is formulated in Advaxis’ Lm antigen-delivery technology – Listeria monocytogenes vectors are taken-up by dendritic cells and the LLO protein (Listeriolysin-O, which possesses a PAMP – pathogen-associated molecular pattern) triggers a potent innate tumor response that augments processing and antigen presentation of the WT1 peptides. GM-CSF is administered as an adjuvant to recruit dendritic cells to the area of vaccination.
Clinical results to date
Galinpepimut-S received FDA Fast Track Designation for AML. In a Phase 2 trial in 22 patients with AML:
- Galinpepimut-S improved overall and progression-free survival in patients with AML in first complete remission (CR1) in comparison to historical data.
- According to the Phase 2 trial results, administration of galinpepimut-S resulted in a median overall survival of 62.5 months in AML patients, which represents a substantial improvement compared to best standard therapies.
- Galinpepimut-S also resulted in an improved median progression-free survival in AML patients of 23.75 months.
- Serial vaccination with galinpepimut-S showed a favorable safety and tolerability profile in this patient population, whose median age was 63 years old.
- Galinpepimut-S elicited immune responses in patients, including CD4+ and CD8+ T cell responses. There was 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 study in patients with AML is planned for 2017.
It also received FDA Fast Track Designation for malignant pleural mesothelioma (MPM). In a randomized, double-blind, placebo-controlled Phase 2 study in MPM patients enrolled a total of 40 patients at Memorial Sloan Kettering Cancer Center and M.D. Anderson Cancer Center. According to 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, median overall survival of 24.8 months was recorded for galinpepimut-S-treated MPM patients, compared to a median 16.6 month overall survival for patients in the control arm.
- Patients with a complete tumor resection and subsequent treatment with galinpepimut-S showed a significant survival benefit
- Galinpepimut-S induced CD8+ and CD4+ T cell activation
- Galinpepimut-S demonstrated a favorable safety and tolerability profile in MPM patients and was well-tolerated by patients in the trial.
A Phase 3 trial in MPM is planned to be initiated later in 2017:
The Phase 3 trial is expected to start this year. Mesothelioma Research News interviewed Angelos Stergiou, MD, ScD, CEO and vice chairman of the board; and Nicholas Sarlis, MD, PhD, senior vice president and chief medical officer of Sellas, to learn more about the upcoming study.
“In our phase 3 clinical trial, we plan to include patients with mesothelioma with disease on one side of the chest (right or left) who would have been able to complete initial treatment with surgery and chemotherapy,” Stergiou and Sarlis told us. “We are hoping to enroll a minimum of 150 patients, but the study could potentially include up to 400 patients, depending on whether certain criteria are met when we ‘look’ at pre-set intervals on how the study evolves.”
Sellas plans to actively treat each patient for at least 13 to 18 months. According to Stergiou and Sarlis, the clinical benefit induced by galinpepimut-S will be measured by overall survival by study’s end, but the trial will also measure time to disease relapse and rate of progression in patients. They estimate that patients receiving galinpepimut-S will live least eight months longer than those treated with standard therapy.
The Company also has a clinical study underway for galinpepimut-S in multiple myeloma, and a combination clinical trial with Bristol-Myers Squibb’s OPDIVO® (nivolumab) in ovarian cancer.