Galinpepimut-S Plus Pembrolizumab Shows Early Activity in Advanced Ovarian Cancer

Pipeline Report | <b>Pipeline Report: July 2021</b>

The combination of galinpepimut-S and pembrolizumab has demonstrated promising clinical immunobiological activity in patients with Wilms Tumor 1–positive, relapsed or refractory, platinum-resistant advanced metastatic ovarian cancer, according to results from an ad-hoc analysis of a phase 1/2 trial.

The combination of galinpepimut-S and pembrolizumab (Keytruda) has demonstrated promising clinical immunobiological activity in patients with Wilms Tumor 1 (WT1)–positive, relapsed or refractory, platinum-resistant advanced metastatic ovarian cancer, according to results from an ad-hoc analysis of a phase 1/2 trial.

At a median follow-up of 15.4 weeks, the combination yielded a disease control rate of 63.6% in a cohort of 11 patients. Moreover, the median progression-free survival (PFS) was 11.8 weeks with this approach, and the landmark 6-month PFS rate by log-rank analysis was 33%. Additionally, the rate of WT1 ovarian tumor positivity among patients was 63.6%. The median overall survival (OS) has not yet been reached.

“Considering the overall poor prognosis in this particular clinical setting and based on the observed median PFS, OS, and DCR in this study, combining galinpepimut-S with the PD-1 inhibitor pembrolizumab appears to be clinically promising as compared with bevacizumab [Avastin]-free salvage chemotherapy regimens and without the toxicity burden associated with the latter,” Angelos Stergiou, MD, ScD, the president and CEO of SELLAS, stated in a press release.

Patients enrolled to the study received treatment with at least 3 doses of galinpepimut-S, the last of which was combined with pembrolizumab. The median age of the participants was 63 years; 66.7% were refractory to or had their second-line therapies fail; and 33.3% of patients had a third-line or later therapy fail. Additionally, 100% of patients were resistant to the standard-of-care platinum-based therapy.

In 3 patients, CD8-positive and CD4-positive T-lymphocytes were isolated from peripheral blood mononuclear cells. In these patients, samples were collected at baseline, as well as 18 weeks after treatment initiation with the investigational agent. Then, the T cells were assayed ex vivo for immune responses against the 4 peptides that comprise galinpepimut-S through intracellular cytokine staining with fluorescence-activated single cell sorting.

The following 5 cytokine channels were utilized for the assessment: interferon-g, TNF-a, interleukin-2, CD107a, and MIP-1b. The peptide re-challenge incubation period was 1 week. At 18 weeks vs pre-vaccination baseline, the assay showed an increase in WT1-specific T-lymphocyte frequencies in peripheral blood at an average of +242% (range, +104% to +386% across 5 cytokines) for CD8-positive cells, and +80.5% (range, +1% to +174%) for CD4-positive cells. Moreover, 66% of patients (n = 2/3) showed evidence of polyfunctional T-cell activation.

All patients in the cohort are still alive and 45.5% of patients (n = 5) are still receiving treatment.

The toxicity profile observed with the combination of galinpepimut-S and pembrolizumab was comparable to the data seen with pembrolizumab alone. However, low-grade, temporary local reactions at the galinpepimut-S injection site were reported, and consistent with prior studies examining the agent.

Enrollment for the study is ongoing, with a target of 20 evaluable patients.

“Based on these early data, it is encouraging to see the induction of WT1-specific T-cell immune responses with the administration of GPS in combination with pembrolizumab with a validated complex ex-vivo immune response assay on peripheral blood from patients with platinum-refractory metastatic ovarian cancer who had undergone numerous prior therapies,” Jeffrey S. Weber, MD, PhD, the deputy director of the Perlmutter Cancer Center at NYU Langone Health, and chair of SELLAS’ Scientific Advisory Board, added in the press release.

Reference

  1. SELLAS reports promising updated clinical data and initial immune response profiles from ongoing phase 1/2 study of galinpepimut-S (GPS) combined with Keytruda for treating WT1+ advanced ovarian cancer. News release. SELLAS Life Sciences Group, Inc. June 30, 2021. Accessed July 7, 2021. https://bit.ly/3jUtsbm