GPS 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 were conducted in patients with AML and thoracic cancers, such as lung cancer and MPM. Following encouraging results in these initial studies, additional Phase 2 trials were launched in hematopoietic cancers and solid tumors. Based on the results of these initial studies, SELLAS believes that GPS is capable of inducing a robust immune response to the antigen.

In patients with advanced cancers over-expressing WT1, GPS is designed to prevent relapses and potentially improve survival rates of patients, while maintaining their quality of life.

Acute Myeloid Leukemia (AML)

Initial clinical studies of GPS 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 GPS in the maintenance setting, i.e. after having successfully achieved their first morphological complete remission (CR1) post-upfront standard antileukemic chemotherapy. The Phase 2 clinical trial met its primary endpoint of an actual overall survival (OS) rate of at least 34%, measured three years into the clinical study, with an actual OS rate of 47.4% being demonstrated at the 3-year timepoint. In the Phase 2 study, in older patients (>60 years), median overall survival reached 35.3 months, and reached 67.6 months in patients across all ages. Compelling CD4 and CD8 reactivity was observed.
• GPS was further independently validated at the Moffitt Cancer Center (MCC) in a more severe AML population – i.e., 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. Initial data from this study showed a median OS of 16.3 months vs. 5.4 months. The final data for the study shows a median OS of 21.0 months, at a median follow-up of 30.8 months, in patients receiving GPS therapy. Those AML CR2 patients being treated with best standard care had a median OS of 5.4 months, which demonstrates a statistically significant difference (p-value < 0.02) for the patients treated with GPS. Final analysis also showed that GPS therapy continued to be well-tolerated throughout the study.
• A Phase 3 clinical trial for AML in the CR2 setting was commenced in January 2020 (ClinicalTrials.gov Identifier: NCT04229979).

Malignant Pleural Mesothelioma (MPM)

MPM was chosen as an indication to study 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.
• 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.

Multiple Myeloma (MM)

Phase 2 open-label 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 proteasome 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.

IN COMBINATION WITH PD-1 INHIBITORS

Ovarian Cancer in Combination with Nivolumab – Completed Phase 1 Study

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

• Combination therapy over 14-weeks with galinpepimut-S every 2 weeks 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
• Median follow-up of 33 months shows 30% of patients being progression free at 2 years (historical controls are 3-10%); WT1-specific IgG observed in 86% of patients (weeks -27) as well as CD4 and CD8 T cell responses

GPS data source: O’Cearbhaill RE, et al. J Clin Oncol. 2018;36[15; Suppl], 5553).

Ovarian Cancer in Combination with Pembrolizumab – Completed Phase 1/2 Study

Phase 1/2 study in combination with Merck’s pembrolizumab (KEYTRUDA®), a PD1 (or checkpoint) inhibitor, in 2^nd or 3^rd line WT1+ relapsed or refractory ovarian metastatic cancer; 17 patients (16 evaluable).

The endpoints of the study include safety, immunobiological response, overall response rate (as measured by “response evaluation criteria in solid tumors” or RECIST), progression free survival and overall survival and other analyses.

• Median Overall Survival (OS) was 18.4 months compared to 13.8 months in a checkpoint inhibitor single agent study in a similar patient population treated with checkpoint inhibitor alone
• Median Progression-Free Survival (PFS) was 12 weeks compared to eight weeks in a checkpoint inhibitor single agent study in a similar patient population treated with checkpoint inhibitor alone
• The overall response rate (ORR) of the trial is 6.3 percent with a disease control rate (DCR), which is the sum of overall response rate and rate of stable disease, of 50.1 percent at a median follow-up of 14.4 months. In a checkpoint inhibitor single agent study in a similar platinum-resistant ovarian cancer patient population treated with a checkpoint inhibitor alone, the observed DCR was 37.2 percent, consistent with a DCR rate increase of approximately 45 percent in the GPS combination with Keytruda over that seen for checkpoint inhibitors alone
• Survival and disease control benefits were observed in patients harboring tumors with any level of detectable PD-L1 expression, i.e., those with Combined Positive Score (CPS) of one or higher, with a DCR of 63.6 percent in patients with a CPS of one or higher
• In the 16 evaluable patients in whom serial peripheral blood samples were available, a correlation was observed between PFS and OS and WT1-specific immune response after GPS vaccination across more than one channel with intracellular cytokine flow-cytometry assays in peripheral blood lymphocytes assaying reactivity against the four pooled WT1 antigens comprising GPS
• The safety profile of GPS in combination with pembrolizumab was similar to pembrolizumab alone, with the only addition of low-grade rapidly resolving local reactions at the GPS injection site, consistent with observations from other GPS clinical studies

(ClinicalTrials.gov Identifier: NCT03761914).

Malignant Pleural Mesothelioma (MPM)

An investigator-sponsored clinical trial (IST) of GPS in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, nivolumab (Opdivo®), in patients with MPM is being conducted at MSKCC. The Phase 1 open-label clinical study is enrolling patients with MPM who harbor relapsed or refractory disease after having received frontline standard of care multimodality therapy with study drug provided by both SELLAS and Bristol-Myers Squibb. The principal investigator for the study is Dr. Marjorie G. Zauderer, MD, Co-Director, Mesothelioma Program, Team Lead, Thoracic Disease Management Team, and Assistant Attending Physician in the Division of Thoracic Oncology, Department of Medicine at MSK.