お知らせ • Nov 07
SELLAS Life Sciences Group, Inc. Presents Positive Key Immunobiological and Clinical Data from Phase 1/2 Trial of galinpepimut-S in Combination with Keytruda in WT1+ Platinum-Resistant Advanced Ovarian Cancer at International Gynecologic Cancer Society 2023 Annual Global Meeting
SELLAS Life Sciences Group, Inc. announced final clinical and immunobiological data from the Phase 1/2 clinical trial of galinpepimut-S (GPS) in combination with pembrolizumab (Keytruda®) in Wilms’ tumor-1 (WT1)-positive platinum-resistant ovarian cancer (NCT03761914). Results are being presented in an e-poster session by Roisin E. O’Cearbhaill, M.D., Research Director, Gynecologic Medical Oncology Service; Clinical Director, Solid Tumor, Cellular Therapy Service; and Associate Attending Physician at Memorial Sloan Kettering Cancer Center, New York, NY, at the 2023 International Gynecologic Cancer Society Annual Global Meeting taking place November 5, 2023 to November 7, 2023, in Seoul, South Korea. GPS is an HLA-unrestricted heteroclitic immunotherapy against WT1, an antigen highly expressed in more than 85% of patients with ovarian cancer. This Phase 1/2 trial was an open-label, multicenter, multi-arm basket study examining the effects of the combination of GPS and pembrolizumab in patients with measurable advanced selected cancers. In the ovarian cancer arm of the study, the effect of the combination was investigated in patients with measurable WT1+ platinum-resistant ovarian cancer relapsed after or refractory to 1st/2nd -or later- line of therapy. This presentation reported clinical efficacy and safety results as well as demographic and disease parameter data in a total of 16 evaluable patients. Historical illustrative comparisons were made between the outcomes in this study and those reported in comparable patients enrolled in the KEYNOTE-028 study, which investigated the effects of pembrolizumab monotherapy. Study highlights include: Patient Characteristics: 17 patients enrolled; 16 safety and efficacy evaluable patients who received at least three doses of GPS and had follow-up cross-sectional imaging (CT/MRI) to determine tumor status. Median age was 65 years (50-76). Median number of prior lines of systemic therapy was two, while 23.5% of enrolled patients (4/17) had received 3-5 prior lines of therapy. Efficacy: Median Overall Survival (OS) was 18.4 months, compared to historical values in comparable patients of 11-14 months with standard of care chemotherapy and 13.8 months with pembrolizumab monotherapy as shown in the KEYNOTE-028 study. Median Progression-Free Survival (PFS) was 2.9 months, compared to eight weeks with pembrolizumab monotherapy as shown in the KEYNOTE-028 study. Actuarial OS rates at 6, 12, and 18 months were 88%, 68%, and 57%, respectively. 43.8% (7/16) of patients achieved stable disease (SD); median duration of SD in these patients was 14.4 months. Disease control rate (DCR), which is the sum of overall response rate (ORR) and rate of SD, was 50.1% (8/16 patients) at a median follow-up of 14.4 months; DCR for pembrolizumab alone in KEYNOTE-028 was 37.2%. ORR was 6.3%. An exploratory analysis of patients harboring tumors with detectable PD-L1 expression, i.e., those with a Combined Positive Score (CPS) >1, suggested the potential correlation between PD-L1 expression as quantified by the CPS in primary tumor samples and median PFS or median OS using two distinct cut-offs (CPS<1 vs CPS=1 and CPS<10 vs CPS=10). Reported data showed that: All patients with CPS<1 progressed vs 36.4% of those with CPS=1; and Patients with CPS<1 had a median PFS of 1.9 months vs 3.8 months in those with CPS=1 and Patients with CPS<1 had a median OS of 3.2 months vs 18.4 months in those with CPS=1. Safety: Treatment-related adverse events (TRAEs) were mostly grade 1-2 and occurred in about 80% of patients receiving the GPS + pembrolizumab combination. Five patients reported 11 serious adverse events (SAEs). One SAE, grade 3 pneumonitis, was considered directly related to pembrolizumab. The remaining 10 SAEs were reported by four patients and all unrelated or unlikely to be related to study drug. No dose-limiting toxicities (DLT) or grade 5 events were reported. Immune Response Profiles: WT1-specific T-cell (CD8 and CD4) immune response (IR) data showed a positive trend over time post-baseline with highest consistency and potential biomarkers for consistency being IFN? and MIP1ß. GPS in combination with pembrolizumab was strongly immunogenic, as evidenced by the positive T-cell responses seen post-vaccination. 42.8% of patients (6/14) achieved CD8 T-cell immune response. 85.7% of patients (12/14) achieved CD4 T-cell immune response. A correlation between WT1 specific T-cell immune responses (CD8 or CD4) and PFS was observed in a subset of analyzed patients with 41% longer PFS in patients with recorded immune response vs without (p=0.025). The multicenter study was sponsored by SELLAS and conducted under a Clinical Trial Collaboration and Supply Agreement with Merck & Co., Inc., Rahway, N.J., USA (known as MSD outside the United States and Canada). Based on data in this e-poster presentation, SELLAS is planning the submission of a full-length manuscript to a peer-reviewed journal during the first half of 2024.