On November 10, 2022 SELLAS Life Sciences Group, Inc. (NASDAQ: SLS) ("SELLAS" or the "Company"), a late-stage clinical biopharmaceutical company focused on the development of novel therapies for a broad range of cancer indications, reported confirmatory top-line clinical data from the final analysis of results from its Phase 1/2 clinical trial of galinpepimut-S (GPS), the Company’s Wilms Tumor-1 (WT1)-targeting peptide immunotherapeutic, in combination with Merck’s anti-PD-1 therapy, pembrolizumab (KEYTRUDA), in patients diagnosed with WT1(+) relapsed or refractory platinum-resistant advanced metastatic ovarian cancer (Press release, Sellas Life Sciences, NOV 10, 2022, View Source [SID1234623666]).

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Data from 17 patients enrolled in the study, 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), have undergone final analysis for safety and efficacy. All enrolled patients were resistant to standard of care platinum-based therapy and 76.5 percent (13/17) of the patients were refractory to or had failed their first- or second-line therapies, with 23.5 percent (4/17) having failed three or more lines of therapy, including one patient (5.9 percent) who failed five previous lines of therapy. Of the 17 patients, 16 received at least three doses of GPS and had follow-up cross-sectional imaging (CT/MRI) to determine tumor status.

Summary of Top-Line Overall Survival and Progression-Free Survival Data:

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.
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.

In the Phase 1/2 study, 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 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 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.

"GPS has been primarily studied as maintenance therapy to provide an overall survival benefit after patients reach a state of minimal residual disease or complete remission. In contrast, in this very difficult to treat patient population with relapsed or refractory measurable advanced platinum-resistant ovarian cancer, who underwent intensive chemotherapy with no apparent enduring clinical benefit, the data suggests that the combination of GPS plus pembrolizumab may be effective in stabilizing active disease. We are excited that both the disease control rate and overall survival results support our belief that GPS has the potential to become an important therapeutic addition to a backbone of checkpoint blockade for WT1(+) ovarian cancer patients, as well as other WT1-expressing tumor types," said Angelos Stergiou, MD, ScD h.c., President and Chief Executive Officer of SELLAS. "SELLAS plans to submit the full dataset at a major medical conference by mid-next year. I would like to extend my sincere gratitude to all patients who have participated in this clinical trial, as well as the collective study teams at SELLAS and Merck," concluded Dr. Stergiou.

"What I find particularly important for patients with advanced platinum-resistant ovarian cancer is that GPS appears to enhance efficacy of checkpoint inhibitors in patients with tumors with detectable PD-L1 expression, whilst demonstrating a low adverse event burden. Until now, in immunotherapy-recalcitrant tumor types, like ovarian cancer, the impression by many experts has been that patients with CPS scores equal to or higher than 10 may be the most probable candidates to derive clinically meaningful benefit from checkpoint inhibitor therapy, either alone or in combination," stated Bruno Bastos, MD, Medical Oncologist and Study Investigator at the Miami Cancer Institute, Physician Lead of the Multiple Tumors/Phase 1 Clinic, and Assistant Professor at the Herbert Wertheim College of Medicine. "Based on these results, it appears that any ovarian cancer patient whose tumor expresses any level of PD-L1, as long as this biomarker is detected, may benefit from the addition of GPS to a checkpoint inhibitor regimen. If these data are confirmed in larger studies in PD-L1+, WT1+ advanced ovarian cancer, it could enable us to bring the benefits of immunotherapy drugs to a broader patient population in a very difficult setting. This is indeed exciting for the ovarian cancer field, as well as patients suffering from other types of WT1+ malignancies," concluded Dr. Bastos.

About Ovarian Cancer
Ovarian cancer is one of the most common gynecologic malignancies and the fifth most frequent cause of cancer death in women in the United States. Over 22,000 cases are diagnosed annually, and there are an estimated 15,500 deaths per year. The majority of patients have widespread disease at presentation. The 5-year survival for advanced-stage disease remains less than 30 percent. Combining GPS with the checkpoint inhibitor pembrolizumab, which beneficially and profoundly alters the tumor microenvironment (TME) is hypothesized to increase the proportion of patients who develop an immune response against their cancer and potentially improve their clinical outcome over checkpoint inhibitors monotherapy, without the burden of additional toxicities in macroscopically measurable malignancies.