The WT1 immunotherapy, originally developed by MSKCC and licensed to SELLAS, incorporates a set of immunogenic peptides that have been shown to stimulate both CD4 and CD8 T-cells. In addition, key amino acids from some of these peptides have been modified to improve their immunogenicity. SELLAS is further optimizing the manufacturing process towards a lyophilized formulation with high stability features. The general principles of the mechanism of action of galinpepimut-S is schematically represented in the graphic below.
WT1 immunotherapy is administered in combination with an adjuvant and an immune modulator (GM-CSF) to improve the immune response to the target. Initial pilot clinical studies have been conducted in patients with AML and thoracic cancers, such as lung cancer and MPM. Based on encouraging results in these initial studies, additional Phase 2 trials were launched in hematopoietic cancers and solid tumors. Results of these initial studies have shown that SELLAS’ WT1 immunotherapy is well-tolerated and capable of inducing a robust immune response to the antigen. Patients enrolled in the AML and MPM trials have shown prolonged survival following active immunization with galinpepimut-S.
In patients with advanced cancers over-expressing WT1, SELLAS’ immunotherapy is designed to prevent relapses and potentially improve survival rates of patients, while maintaining their quality of life. Clinical studies conducted at MSKCC have shown strong proof of concept, including compelling survival findings, and a well-tolerated safety profile.
Acute Myeloid Leukemia (AML)
Initial clinical studies of galinpepimut-S were conducted in AML due to the high levels of WT1 expression observed in this tumor type and the deep institutional experience of MSKCC with AML.
- Phase 1 and Phase 2 studies were conducted with 9 and 22 patients, respectively. These patients were treated with galinpepimut-S in the maintenance setting, i.e. after having successfully achieved their first morphological complete remission (CR1) post-upfront standard antileukemic chemotherapy. Of these total 31 patients 16 (52%) remain alive with a median OS of the Phase 2 study patients of 67.6 months.
- Galinpepimut-S was further independently validated at the Moffitt Cancer Center (MCC) in a more severe AML population in patients who had reached their second complete remission (CR2, post 2nd line chemotherapy), where it showed statistically significant clinical benefit when compared with a cohort at the same institution contemporaneously treated with best standard therapy, leading to a median survival of 16.5 months vs. 5.5 months. Disease free survival was 10.6 months vs 4.4 months with standard treatment.
- A Phase 3 clinical trial for AML in the CR2 setting is currently being scheduled, pending funding availability.
Malignant Pleural Mesothelioma (MPM)
MPM was chosen as a clinical trial setting due to the high levels of expression of WT1 in patients with this tumor type.
- A 41-patient Phase 2, double-blind, randomized study performed at MSKCC and MD Anderson Cancer Center and co-sponsored by the Department of Defense (DOD), demonstrated a well-tolerated safety profile.
- The most recent analysis shows median OS was 22.8 months in the GPS arm vs. 18.3 months in the control arm, (HR: 0.79), with a median follow-up of 17.2 months.
- A Phase 3 clinical trial for MPM is currently being scheduled, pending funding availability.
Multiple Myeloma (MM)
Phase 2 Study in high-risk patients after successful front-line therapy
20 patients enrolled; 18 evaluable.
- 88% actuarial OS at 18 months and median OS not reached.
- Median PFS of 23.6 months.
- All evaluable patients had evidence of minimal residual disease (MRD) after autologous stem cell transplantation (ASCT) and 15/18 patients also had high-risk cytogenetics as well as additional unfavorable clinical characteristics at diagnosis.
- Typically, patients with the above features exhibit PFS rates that do not exceed 12 months following ASCT, even while on maintenance therapy with immunomodulatory drugs (IMIDs) or proteasom inhibitors.
Galinpepimut-S data source: Koehne G, et al. 44th Ann. Meeting of the European Society for Blood and Marrow Transplantation (EBMT), 2018; Abstr. # O132.
Ovarian Cancer
Phase 1/2 study in the maintenance setting in combination with nivolumab (OPDIVO®), an inhibitor of Programmed cell Death protein 1 (PD1)
11 patients (10 evaluable) with recurrent ovarian cancer who are in second or greater clinical remission
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Combination therapy over 14-weeks with galinpepimut-S every 2 wks x 6 inoculations in combination with 7 infusions of nivolumab every 2 weeks
- No additional toxicity burden above and beyond what would be expected with nivolumab alone
- PFS rate at 1 year since initiation of salvage chemotherapy was 70% for patients who received >2 doses of the combination (n=10), which compared favorably with historical 1-yr PFS rates of 43-50% in this setting
Galinpepimut-S data source: O’Cearbhaill RE, et al. J Clin Oncol. 2018;36[15; Suppl], 5553).
Various Advanced Malignancies
Phase 1/2 study (5-arm ‘basket’ trial) in the metastatic/blastic disease setting in combination with pembrolizumab (KEYTRUDA®), a PD1 inhibitor.
Currently enrolling patients in five cancer indications, including AML (on hypomethylating agents having achieved only morphological partial response in front-line), and advanced, recurrent solid tumors (ovarian Ca, colorectal Ca -cohort enriched in but not exclusive to patients with microsatellite instability-low [MSI-L], small cell lung Ca, and triple-negative breast Ca). The study is planned to enroll up to 90 patients in various centers in the United States.
This study will assess the efficacy and safety of the combination, comparing overall response rates (ORRs – by RECIST criteria) and immune response markers achieved with the combination versus prespecified rates based on those seen with pembrolizumab alone in comparable patient populations.
(ClinicalTrials.gov Identifier: NCT03761914).
For more information on the WT1 program, please see “Galinpepimut-S: Publications and Presentations” on this website.