Galinpepimut-S Plus Nivolumab Provides Survival Benefits With Acceptable Safety in Mesothelioma

Author(s):

The combination of galinpepimut-S and nivolumab provided positive survival outcomes with an acceptable safety profile in patients with malignant pleural mesothelioma who were refractory to or relapsed after at least 1 line of standard treatment.

Dragan Cicic, MD

The combination of galinpepimut-S and nivolumab (Opdivo) provided positive survival outcomes with an acceptable safety profile in patients with malignant pleural mesothelioma who were refractory to or relapsed after at least 1 line of standard treatment, meeting safety and efficacy end points of a completed phase 1 trial (NCT04040231).¹

The median overall survival (OS), which was calculated as the time from the cessation of most recent prior therapy until confirmed death or most recent data update for those still alive, was 17.6 months (70.3 weeks) in patients who received the doublet (n = 9). For all 10 patients, 9 who received the combination and 1 who received the targeted cancer vaccine alone, the median OS was 13.5 months (54.1 weeks). Notably, those who entered the study with stage IV disease experienced a median OS of 15.6 months (62.3 weeks).

The median progression-free survival (PFS) in all patients was 11.9 weeks. Additionally, the disease control rate (DCR) was 30%, with 3 patients achieving stable disease by RECIST criteria; these patients experienced up to a 17% reduction in tumor volume.

All patients experienced toxicities with treatment, with 70% experiencing treatment-related adverse effects (AEs). Sixty percent of patients experienced toxicities associated with nivolumab and 30% had toxicities related to the vaccine. All toxicities associated with galinpepimut-S were grade 1 and included skin induration at injection site/injection site reaction with or without fatigue (n = 2), as well as dizziness (n = 1) and non-cardiac chest pain (n = 1).

“It is important to note that the positive survival outcomes seen in this study are accompanied with a safety profile which is similar to that of the checkpoint inhibitor alone,” Dragan Cicic, MD, senior vice president of Clinical Development at SELLAS Life Sciences, stated in a press release. “It is rare for a drug used to treat advanced cancers to result in no toxicities higher than grade 1. Interestingly, patients in this trial whom low toxicities were observed all had survival at the median or higher.”

Galinpepimut-S was designed to target malignancies that overexpress Wilms Tumor 1 antigen; it is comprised of 4 peptide chains, 2 of which are modified chains that elicit a strong, innate immune response against this antigen and access a wide range of human leukocyte antigens.² The vaccine possesses the potential to detect and kill cancer cells, as well as provide ongoing support to the immune system so that it can continue to eliminate recurring and residual disease.

Patients who received a pathologic diagnosis of malignant pleural mesothelioma at Memorial Sloan Kettering were enrolled to the phase 1 trial.³ To be eligible, they needed to be at least 18 years of age, have a Karnofsky performance status of at least 70%, have measurable or evaluable disease, and be positive for WT1 on immunohistochemistry. They also must have received at least 1 prior line of pemetrexed-based chemotherapy and have progressed or been refractory to the treatment.

They could not have previously received a checkpoint inhibitor, nor could they have active hepatitis B or C virus or another autoimmune disease requiring systemic steroids in the past 2 years.

The primary end point of the trial was to determine the maximum tolerated dose for the combination, and to evaluate early efficacy.

Among the 10 evaluable patients, the median age was 69 years; 8 patients were male and 2 were female.1 More than half of patients (60%) entered the study with stage III (n = 2) or IV (n = 4) disease. One patient had stage I disease and 3 patients had stage II disease. Notably, all patients had malignant pleural mesothelioma epithelioid and/or sarcomatoid variant, which is known to express WT1.

A previous update from the trial reported data on 8 patients and showed a median OS of 40.9 weeks; in the 7 patients who had received the combination, the median OS was 45.7 weeks.⁴ In all 8 patients, the median PFS had been 11.1 weeks; in the 7 who received the doublet, the median PFS was 11.9 weeks. No dose-limiting toxicities were reported, nor were any grade 3 or 4 adverse effects observed.

Data from another phase 1/2 trial (NCT03761914) examining galinpepimut-S in combination with pembrolizumab (Keytruda) showed that the doublet induced an overall response rate of 7.7% in patients with WT1-positive relapsed or refractory advanced metastatic ovarian cancer who were resistant to platinum chemotherapy (n = 13).⁵ At a follow-up of 43.1 weeks, the median PFS in this group was 12 weeks and the median OS was not yet reached. The DCR reported with the combination was 53.9%.

“In our [galinpepimut-S] trials completed in previous years, we have observed and reported increased survival in the maintenance therapy setting, which is the primary setting for our therapy. This year, we have seen in 2 studies where galinpepimut-S appears to increase the survival benefit in active disease when combined with checkpoint blockade drugs, one with relapsed or refractory WT1-positve ovarian cancer, and now in relapsed/refractory WT1-positive mesothelioma,” Angelos Stergiou, MD, ScDhc, president and chief executive officer of SELLAS Life Sciences, stated in a press release.¹ “We believe that these observed survival benefits in the active disease setting further confirms the strong biological effect of galinpepimut-S in even the most challenging settings.”