Acute Myeloid Leukemia (AML)

COMPLETED PHASE 2 TRIAL OF GPS MONOTHERAPY IN AML PATIENTS IN FIRST COMPLETE REMISSION (CR1)
COMPLETED PHASE 2 TRIAL OF GPS MONOTHERAPY IN AML PATIENTS IN SECOND COMPLETE REMISSION (CR2)
ONGOING PHASE 3 TRIAL (REGAL STUDY) OF GPS MONOTHERAPY IN AML PATIENTS IN CR2

Phase 2 trial results in AML patients in their first complete remission (CR1) showed a median OS of 67.6 months (all ages) for patients receiving GPS in the maintenance setting, which represents a substantial improvement compared to best standard therapies. The patients’ median age was 63 years old. The results also showed a trend in improved clinical outcomes in patients who mounted an immune response with GPS compared to those patients who did not (Maslak PG, et al. Blood Adv. 2018;2:224-34). Broadly similar results were obtained in a pilot study of GPS in a more advanced setting, i.e., in AML patients who had relapsed, received standard second line therapy and were able to achieve their second complete remission (CR2). In that study, the patients’ median age was 74 years old. Initial data showed that administration of GPS in the maintenance setting resulted in a median OS of 16.3 months (all ages) versus 5.4 months in post-hoc matched, contemporaneously treated patients (P = 0.0175) (Brayer J, et al. Am J Hematol. 2015;90:602-7). Final data from the study shows a median OS of 21.0 months, at a median follow-up of 30.8 months, in patients receiving GPS therapy versus 5.4 months OS for those AML CR2 patients being treated with best standard care, a statistically significant difference (p-value < 0.02) for the patients treated with GPS. In both studies, serial active immunization with GPS showed a well-tolerated safety profile. In addition, GPS elicited immune responses in patients, including CD4+ and CD8+ T cell responses.

Based on the above data and following review by the FDA, a pivotal Phase 3 clinical trial, the REGAL study, for AML patients in CR2 was commenced in January 2020. The REGAL study is a 1:1 randomized, open-label study comparing GPS monotherapy in the maintenance setting to investigators’ choice best available treatment in AML patients who have achieved hematologic complete remission, with or without thrombocytopenia (CR2/CR2p), after second-line antileukemic therapy and who are deemed ineligible for or unable to undergo allogeneic stem-cell transplantation. The primary endpoint is the overall survival (OS) from the time of study entry. Secondary endpoints include leukemia-free survival, antigen-specific T-cell immune response dynamics, measurable residual disease by multigene array, and assessments of AML clonal evolution and inflammasome molecular signatures in the tumor microenvironment in bone marrow biopsy samples. The study is expected to enroll approximately 125 to 140 patients across approximately 85 clinical sites in the United States, Europe and Asia.

OVARIAN CANCER

ONGOING PHASE 1/2 TRIAL OF GPS IN COMBINATION WITH KEYTRUDA® (PEMBROLIZUMAB) IN OVARIAN CANCER

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). GPS is being administered in combination with Merck’s' anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in a Phase 1/2 trial. The primary indication studied was ovarian cancer (second or third line). The Phase 1/2 trial utilized a combination of GPS plus KEYTRUDA in patients with WT1-positive relapsed or refractory tumors. This study assessed 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 was initiated in December 2018 (ClinicalTrials.gov Identifier: NCT03761914). The total number of enrolled patients was 17 of which 16 were evaluable. On November 10, 2022, SELLAS reported final topline clinical data.. An analysis of clinical outcomes showed a disease control rate (DCR), 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 45 percent in the GPS combination with pembrolizumab over that seen for checkpoint inhibitors alone. Importantly, 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. The DCR is 63.6 percent in patients with a CPS of one or higher in this study. Median progression-free survival (PFS) was 12 weeks compared to 8 weeks for a checkpoint inhibitor alone in a similar patient population.. 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 a checkpoint inhibitor alone. Patients with a CPS score of less than one showed a median OS of 3.2 months vs. patients with a CPS greater than or equal to one who had a median OS of 18.4 months and, as it relates to time to progression, patients with a CPS score of less than one had a median PFS of 1.9 months and patients with a CPS score of greater than or equal than one showed a median PFS of 3.8 months. 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. These data were consistent with those seen in previous studies of 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.

COMPLETED OPEN-LABEL, NON-RANDOMIZED PHASE 1/2 CLINICAL STUDY EVALUATING THE SAFETY AND EFFICACY OF GPS 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 enrolled 11 patients with recurrent ovarian cancer who are in second or greater clinical remission at MSKCC. Patients enrolled in the study received the combination therapy during the study’s 14-week treatment period. Individuals who have not progressed by the end of this period also received a maintenance course of the GPS. Repeated vaccination with GPS for a total of 6 inoculations in combination with 7 infusions of nivolumab was shown not to add toxicity burden above and beyond what would be expected with nivolumab alone; therefore, the primary endpoint of the study (safety of the combination) was met. Moreover, the 1-year landmark progression-free survival (PFS) rate was 70% for patients who received >2 doses of GPS and nivolumab (n=10), which compared favorably with a historical rate of 43-50% in this setting (O’Cearhaill RE, et al. J Clin Oncol. 2018;36[15; Suppl], 5553). Median follow-up of 33 months showed 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. These data have supported the rationale for further study of GPS in combination with PD1 inhibitors in patients with advanced ovarian cancer.

Malignant Pleural Mesothelioma (MPM)

COMPLETED RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2 STUDY OF GPS MONOTHERAPY IN A TOTAL OF 41 MPM PATIENTS ENROLLED AT MSKCC AND M.D. ANDERSON CANCER CENTER.

According to the final analysis of the Phase 2 MPM study data of GPS with a median follow up of 17.2 months, median OS of 22.8 months was observed for GPS-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;23:7483-9). In the datasets from both these analyses, GPS induced CD8+ and CD4+ T cell activation. GPS also demonstrated a well-tolerated safety profile in MPM patients.

ONGOING PHASE 1 OPEN LABEL STUDY OF GPS IN COMBINATION WITH NIVOLUMAB IN MPM PATIENTS

In February 2020, an investigator-sponsored clinical trial (IST) of GPS in combination with Bristol-Myers Squibb’s anti-PD-1 therapy, nivolumab (Opdivo®), in patients with malignant pleural mesothelioma (MPM), which is being conducted at MSKCC, was commenced. Study drug is being provided by both SELLAS and Bristol-Myers Squibb for this Phase 1 open-label clinical study of GPS in combination with nivolumab in patients with MPM who harbor relapsed or refractory disease after having received frontline standard of care multimodality therapy. The purpose of the trial is to determine if the administration of GPS in combination with nivolumab has the potential to demonstrate antitumor immune responses and meaningful clinical activity in the presence of macroscopic disease in MPM patients. The study will also investigate the tolerability of the combination, evaluate the immunogenicity of the two agents administered together, by CD4+ and CD8+ T-lymphocytes (both peripherally and at the tumor site), and gauge the degree of clinical benefit by assessment of the overall response rate with the combination in comparison with that reported with nivolumab alone in historical comparable patient populations. In a randomized, controlled, blinded Phase 2 clinical trial in MPM patients completed in 2017, GPS monotherapy, given as maintenance after first line tumor-debulking multimodality treatment, demonstrated meaningful clinical activity with median survival of 22.8 months vs. 18.3 months in the control group (N=41) and with associated sustained immune responses (both CD4+ and CD8+) against the WT1 antigen while adverse events were mainly comprised of low grade reactions at the site of the injection. On June 6, 2022, SELLAS reported encouraging updated clinical data for eight patients enrolled in the study. Of the eight patients, seven received at least three doses of GPS, the last of which was given in combination with nivolumab. All enrolled patients have received and progressed with, or were refractory to, frontline pemetrexed-based chemotherapy. Of the eight evaluable patients, 75 percent of the patients entered the study as Stage III or IV patients, with 50 percent of patients entering as Stage IV. Initial tumor stages were II (two patients), III and IIIB (two patients) and IV (four patients). All patients had the MPM epithelioid and/or sarcomatoid variant, a tumor which is universally expressing Wilms Tumor 1 (WT1), one of the most widely expressed cancer antigens, ranked by the National Cancer Institute as the top priority among cancer antigens for immunotherapy. Median overall survival (OS) calculated as the time from the cessation of the most recent previous therapy until confirmed death or most recent data update for patients who are still alive (50 percent of patients) was 40.9 weeks (9.4 months) for all eight patients and 45.7 weeks (10.5 months) in patients who received the combination therapy (seven out of eight patients). The median progression-free survival (PFS) was 11.1 weeks for all eight patients and 11.9 weeks in patients who received the combination therapy. The safety profile of the GPS-nivolumab combination was similar to that seen with nivolumab alone, with the addition of only low-grade, temporary local reactions at the GPS injection site, consistent with previously performed clinical studies with GPS. No Grade 3/4 toxicities were observed for GPS and there were no dose-limiting toxicities. Final data in the clinical trial is expected by the end of 2022.

Multiple Myeloma (MM)

COMPLETED OPEN-LABEL PHASE 2 STUDY OF GPS MONOTHERAPY IN 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 (median follow-up at 18 months for survivors). 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. Administration of GPS in the post-ASCT maintenance setting (along with lenalidomide) also resulted in cross-epitope reactivity in the majority of patients, whereas strong correlations were observed between immune response to WT1 antigens and clinical response (achievement of complete response/very good partial response [CR/VGPR]) at the time of completion of the inoculation series (Koehne G, et al. 44th Ann. Meeting of the European Society for Blood and Marrow Transplantation (EBMT), 2018; Abstr. # O132). GPS 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 a historical cohort of MM patients with high-risk cytogenetics published by the Spanish PETHEMA group from the PETHEMA Network No. 2005-001110-41 trial, which included MM patients with high-risk cytogenetics and MRD+ status post-ASCT and on continuous thalidomide maintenance.