Acute Myeloid Leukemia (AML)
IN A PHASE 2 TRIAL IN AML PATIENTS, IN FIRST COMPLETE REMISSION, GALINPEPIMUT-S AS MAINTENANCE MONOTHERAPY WAS SHOWN TO IMPROVE OS IN COMPARISON TO HISTORICAL DATA. RESULTS WERE CORROBORATED BY A CONTROLLED PILOT STUDY IN AML PATIENTS IN SECOND COMPLETE REMISSION (CR2).
According to the Phase 2 trial results in AML patients in their first complete remission (CR1), administration of galinpepimut-S 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 evidenced a trend in improved clinical outcomes in patients who mounted an immune response with galinpepimut-S 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 galinpepimut-S 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 galinpepimut-S 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 galinpepimut-S showed a well-tolerated safety profile. In addition, galinpepimut-S elicited immune responses in patients, including CD4+ and CD8+ T cell responses. Based on the above data and following review by the FDA, a Phase 3 program for AML patients in CR2 is currently being scheduled, pending funding availability.
Malignant Pleural Mesothelioma (MPM)
SELLAS RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED PHASE 2 STUDY IN MPM PATIENTS ENROLLED A TOTAL OF 41 PATIENTS AT MSKCC AND M.D. ANDERSON CANCER CENTER.
According to the final analysis of the Phase 2 MPM study data of galinpepimut-S with a median follow up of 17.2 months, median OS of 22.8 months was observed for galinpepimut-S-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, galinpepimut-S induced CD8+ and CD4+ T cell activation. Galinpepimut-S also demonstrated a well-tolerated safety profile in MPM patients. A Phase 3 clinical study in MPM has been planned.
Multiple Myeloma (MM)
SELLAS HAS REPORTED UPDATED POSITIVE PHASE 2 DATA FROM ITS WT1 IMMUNOTHERAPEUTIC ANTI-CANCER TREATMENT, GALINPEPIMUT-S, WHICH INDICATE A MEANINGFUL CLINICAL BENEFIT AMONG 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 galinpepimut-S 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). SELLAS’ results compare favorably with an unmatched cohort of MM patients with high-risk cytogenetics published by the Spanish PETHEMA group from the PETHEMA Network No. 2005-001110-41 trial. SELLAS’ galinpepimut-S therapy 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 the aforementioned historical cohort, which included MM patients with high-risk cytogenetics and MRD+ status post-ASCT and on continuous thalidomide maintenance.
Ovarian Cancer
SELLAS’ OPEN-LABEL, NON-RANDOMIZED PHASE 1/2 CLINICAL STUDY EVALUATED THE SAFETY AND EFFICACY OF GALINPEPIMUT-S 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 galinpepimut-S. Repeated vaccination with galinpepimut-S 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 galinpepimut-S 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). These data significantly strengthened the rationale for further study of galinpepimut-S in combination with PD1 inhibitors in patients with advanced ovarian cancer.
Hematology And Solid Tumors
GALINPEPIMUT-S AND KEYTRUDA® (PEMBROLIZUMAB) COMBINATION TRIAL (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). SELLAS' Wilms tumor-1 (WT1)-targeting peptide immunotherapeutic agent, galinpepimut-S, is being administered in combination with MSD's anti-PD-1 therapy KEYTRUDA® (pembrolizumab) in a Phase 1/2 trial currently enrolling patients in five cancer indications, including both hematologic malignancies and solid tumors. The Phase 1/2 trial utilizes a combination of galinpepimut-S plus KEYTRUDA in patients with WT1-positive relapsed or refractory tumors. Specifically, the study is exploring the following cancer indications: colorectal (arm enriched in but not exclusive to patients with microsatellite instability-low [MSI-L]), ovarian, small cell lung, triple-negative breast, and AML. 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).
Breast Cancer - NeuVaxTM (Nelipepimut-S)
SELLAS-SUPPORTED 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.
SELLAS IS SUPPORTING A 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 enrolled100 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 and is expected to be reached in Q4, 2019 (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.
SELLAS IS SUPPORTING AN 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 are being 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 NeuVax vaccine on NeuVax -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.