Galinpepimut-S Shows Early Promise With Checkpoint Inhibition for 2 WT1-Positive Solid Tumors

Encouraging early data were observed with galinpepimut-S (GPS), the Wilms Tumor-1 (WT1)-targeting peptide immunotherapeutic, in combination with immune checkpoint inhibitors as treatment of patients with 2 different solid tumor types who had exhausted standard therapeutic options, announced SELLAS Life Sciences Group, Inc.

GPS in combination with pembrolizumab (Keytruda) induced promising disease control rate (DCR) and progression-free survival (PFS) data in patients with advanced WT1-positive ovarian cancer, while GPS combined with nivolumab (Opdivo) generated clinically intriguing activity in patients with mesothelioma.

“These early data confirm the tolerability profile seen in earlier studies of GPS, which is one of the primary endpoints in these solid cancer trials, in a variety of cancer indications, even in the most refractory patients who underwent numerous prior therapies,” said Jeffrey S. Weber, MD, PhD, deputy director of the Perlmutter Cancer Center at New York University (NYU)-Langone Health, co-director of its Melanoma Research Program Center and Chair of SELLAS’ Scientific Advisory Board, in a statement. “These safety findings are accompanied by promising early indications of an efficacy signal for patients with advanced metastatic disease, whose management is extremely challenging even with checkpoint inhibitor monotherapy.”

The first study is a phase 1/2 basket trial of GPS plus pembrolizumab, and the first set of evaluable patients had second- or third-line WT1-positive relapsed/refractory metastatic ovarian cancer. Among these 8 patients, the DCR was 87.5% with a median follow-up of 9.4 weeks. At 6 weeks, all patients were free of disease progression for a PFS rate of 100%.

The rate of WT1-positivity was approximately 70% during the screening period, according to findings using a validated immunohistochemistry (IHC) assay. Six of the patients are still receiving therapy on the study, and the target enrollment is 20 patients.

The second study, a phase 1 investigator-sponsored study of GPS with nivolumab, included 3 patients with macroscopic measurable deposits of malignant pleural mesothelioma (MPM) who were wither refractory to or relapsed after first-line tri-modality standard therapy in the first set of evaluable patients. These patients had a median PFS of at least 10 weeks since the start of therapy. Considering the lack of effective treatments for patients with primary refractory disease, PFS prolongation is considered clinically meaningful when the interval is greater than 8 weeks.

All patients in the study had the epithelioid variant of MPM which is a tumor that universally expresses WT1. GPS appeared to be appropriately immunogenic, which led to the emergency of WT1-specific CD4-positive T-memory cell responses 3 months post-initiation of treatment. A total of 10 patients with MPM are expected to enroll to the trial to complete the target recruitment.

The safety profile of both GPS regimens was similar to what has been observed previously with checkpoint inhibitors alone. The addition of this therapy induced only low grade, transitory local reactions at the site of injection, which is consistent with findings from previous clinical trials.

By the end of the second quarter of 2021, the company expects to have more mature clinical and immunobiological data from both of these clinical trials.

“We are encouraged by the data shown in these 2 studies of GPS in combination with checkpoint inhibitors and look forward to additional data from these studies,” stated Dragan Cicic, MD, senior vice president, Clinical Development of SELLAS. “We now have early evidence that supports further expanding the field of potential GPS indications into solid cancers with high rates of WT1 positivity. GPS has previously been shown to invoke multi-epitope, broad cross-reactivity along the full-length of the WT1 protein, suggestive of epitope spreading, and immunologically mediated cancer cell destruction, which are hallmarks of an effective cancer vaccine. The scientific rationale in combining GPS with checkpoint inhibitors is the immunbiologic and pharmacodynamic synergy between the two agents, whereby the negative influence of the tumor microenvironment is mitigated by checkpoint inhibitors and thus allowing the patients’ own immune cells specifically sensitized against WT1, by GPS, to invade and destroy cancerous cells.”

_References

_{SELLAS announces promising initial clinical data for galinpepimut-S (GPS) in combination with checkpoint inhibitors in two solid tumor indications. News Release. SELLAS Life Sciences Group. December 21, 2020. Accessed December 22, 2020.}