Sellas Pipeline

Expanded Development Pipeline

PROGRAM
PRECLINICAL
PHASE 1
PHASE 2
PHASE 3

Galinpepimut-S

Acute Myeloid Leukemia (AML)
Basket Study in Combination w/pembriolizumab
Malignant Pleural Mesothelioma (MPM) in combination with nivolumab
Malignant Pleural Mesothelioma (MPM)
Multiple Myeloma (MM)***
Ovarian (combination w/ nivolumab)

NELIPEPIMUT-S

Breast Cancer in Combination w/ trastuzumab (HER2 1+/2+)

GPS Clinical Trials

Acute Myeloid Leukemia (AML)

IN A PHASE 2 TRIAL IN AML PATIENTS, IN FIRST COMPLETE REMISSION, GPS AS MAINTENANCE MONOTHERAPY WAS SHOWN TO IMPROVE OVERALL SURVIVAL (OS) IN COMPARISON TO HISTORICAL DATA. A CONTROLLED PILOT STUDY IN AML PATIENTS IN SECOND COMPLETE REMISSION (CR2) ALSO SHOWED IMPROVEMENT IN OS.

According to the Phase 2 trial results in AML patients in their first complete remission (CR1), administration of GPS in the maintenance setting resulted in a median OS of 67.6 months (all ages), 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. 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). 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 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 116 patients across approximately 50 clinical sites in the United States and Europe.

GPS IN COMBINATION WITH KEYTRUDA® (PEMBROLIZUMAB) BASKET STUDY (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). GPS is being administered in combination with MSD's anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in a Phase 1/2 trial and is currently enrolling patients in two indications, ovarian cancer (second or third line) and colorectal cancer (third or fourth line), to be followed by AML (patients unable to attain deeper morphological response than partial on hypomethylating agents and who are not eligible for allogeneic hematopoietic stem cell transplant), triple negative breast cancer (second line) and small cell lung cancer (second line). The Phase 1/2 trial utilizes a combination of GPS plus KEYTRUDA in patients with WT1-positive relapsed or refractory tumors. 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 was initiated in December 2018 (ClinicalTrials.gov Identifier: NCT03761914). The study is planned to enroll approximately 90 patients at up to 20 centers in the United States.

Malignant Pleural Mesothelioma (MPM)

RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2 STUDY 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.

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

SELLAS, together with MSK and Bristol-Myers Squibb are planning a Phase 1 investigator sponsored 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, with study drug provided by both SELLAS and Bristol-Myers Squibb. This study will commence in the first quarter of 2020. 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.

Multiple Myeloma (MM)

OPEN-LABEL PHASE 2 STUDY 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.

Ovarian Cancer

OPEN-LABEL, NON-RANDOMIZED PHASE 1/2 CLINICAL STUDY EVALUATED 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 shows 30% of patients being progression free at 2 years (historical controls are 3-10%); WT1-specific IgG observed in 86% of patients (wks -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.

NPS Clinical Trials

Breast Cancer

RANDOMIZED, BLINDED, CONTROLLED INVESTIGATOR-SPONSORED TRIAL (IST) WITH NPS IN COMBINATION WITH TRASTUZUMAB (HERCEPTIN®; GENENTECH/ROCHE) VS. TRASTUZUMAB ALONE IN HER2 1+/2+ BREAST CANCER PATIENTS. RESULTS DEMONSTRATED A STRONG EFFICACY SIGNAL IN THE TRIPLE-NEGATIVE BREAST CANCER (TNBC) COHORT WITH A MANAGEABLE TOXICITY PROFILE

This Phase 2b clinical trial is a randomized, multicenter, investigator-sponsored, 275 patient study which enrolled HER2 1+ and 2+, including triple-negative breast cancer (TNBC) patients, HLA A2+, A3+, A24 and/or A26, node positive, and high-risk node negative breast cancer patients. Eligible patients were randomized to receive NPS + GM-CSF + trastuzumab or trastuzumab + GM-CSF alone. (ClinicalTrials.gov Identifier: NCT01570036). Based on the final analysis of the full data-set from the clinical trial, and with a median follow-up of 25.7 months, no safety-related statistically significant differences were seen between the treatment and control arms in the rate of grade 1-3 adverse events of either local or systemic nature, while no grade 4/5 toxicities were observed in either arm. Also, there was no statistically significant difference between the treatment arms in the cardiac ejection fraction measured at baseline, as well as at four additional time-points up to 24 months post-randomization. In the intent-to-treat (ITT) population, the disease-free survival (DFS) landmark rate at 24 months was in favor of the combination (NPS plus trastuzumab) arm (89.8%) versus trastuzumab alone (83.8%) with a hazard ratio of 0.62 (P=0.18). In the 97-patient TNBC cohort, the DFS landmark rate at 24 months for patients treated with NPS plus trastuzumab was 92.6% compared to 70.2% for those treated with trastuzumab alone, a clinically and statistically significant improvement with a hazard ratio of 0.26 (P=0.01). In the TNBC cohort, there was a statistically significant reduction of 71.9% (P=0.01) in the frequency of clinically detected recurrences in those patients treated with the combination (NPS plus trastuzumab) versus trastuzumab alone (Hickerson A, et al. J Clin Oncol. 2019;37[Suppl 8], Abstr. 1). The above data support SELLAS’ ongoing discussions with the U.S. Food and Drug Administration (FDA) on the most appropriate registration-enabling development path for NPS in TNBC. This IST was a clinical collaboration between SELLAS, Genentech/Roche, and the Henry M. Jackson Foundation.

FULLY ENROLLED, ONGOING RANDOMIZED, BLINDED, CONTROLLED IST WITH NPS IN COMBINATION WITH TRASTUZUMAB (HERCEPTIN®; GENENTECH/ROCHE) VS. TRASTUZUMAB ALONE IN HER2-POSITIVE (HER2 IHC3+) PATIENTS.

This multi-center, prospective, randomized, single-blinded Phase 2 trial has enrolled 100 patients with a diagnosis of HER2-positive (HER2 IHC3+) breast cancer who were HLA A2+ or HLA A3+ and 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 were randomized to receive NPS + GM-CSF plus trastuzumab or GM-CSF plus trastuzumab alone. The primary endpoint of the study is disease-free survival (ClinicalTrials.gov Identifier: NCT02297698). 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.

FULLY ENROLLED ONGOING RANDOMIZED, BLINDED, CONTROLLED IST WITH NPS PLUS GM-CSF VS. GM-CSF ALONE 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 were randomized to one of two arms: NPS plus GM-CSF or GM-CSF alone. The primary endpoint is immunologic and will evaluate the effect of the NPS on NPS -specific cytotoxic T lymphocytes to determine whether long-lasting immunity is induced (ClinicalTrials.gov Identifier: NCT02636582). 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.