Galinpepimut-S Plus Nivolumab Extends Survival in Malignant Pleural Mesothelioma

The combination of galinpepimut-S and nivolumab (Opdivo) was found to extend survival in patients with malignant pleural mesothelioma who were either refractory to, or who had relapsed after, at least 1 line of standard therapy, according to updated data from a phase 1 trial (NCT04040231).¹

The median overall survival (OS), which was calculated as time from the cessation of the most recent prior therapy until confirmed death or most recent data update for those who are still alive, was 40.9 weeks for all 8 patients included in the trial, and 45.7 weeks for those who received the doublet (n = 7/8). Moreover, the median progression-free survival (PFS) was 11.1 weeks for all patients and 11.9 weeks for those who received the regimen.

The safety profile of the combination was comparable to that observed with single-agent nivolumab. The only difference was the temporary local reactions that occurred at the injection site for galinpepimut-S, which is consistent with what has been reported in prior studies evaluating the agent; however, these reactions were noted to be low grade.

Moreover, no grade 3 or 4 adverse effects (AEs) were reported with galinpepimut-S, nor were any dose-limiting toxicities observed.

“[These] updated data [are] very encouraging, as it not only confirms our data reported in June 2021, but now reflects an increased survival benefit even though almost all additionally enrolled patients had grade III and IV malignant mesothelioma,” Angelos Stergiou, MD, ScDhc, president and chief executive officer of SELLAS Life Sciences Group, Inc., stated in a press release.

Galinpepimut-S targets malignancies that are characterized by an overexpression of Wilms Tumor 1 (WT1) antigen; it is comprised of 4 peptide chains, 2 of which are modified chains that induce a strong, innate immune response against WT1 antigen and access a wide range of human leukocyte antigen types.² The vaccine is hypothesized to have the potential to identify and eliminate cancer cells, as well as provide ongoing support and memory to the immune system so it can continue to target and eliminate recurring disease and residual cancer cells.

The phase 1 trial enrolled patients with a pathologic diagnosis of malignant pleural mesothelioma with positive immunohistochemical staining for WT1 within 60 days of treatment initiation.³ Patients were required to be at least 18 years of age, have a Karnofsky performance status of at least 70%, measurable disease, and have previously received at least 1 course of pemetrexed-based chemotherapy.

Patients could not have previously received checkpoint inhibitors, have known active hepatitis B or C virus, serious unstable medical illness or another active cancer, a known history of human immunodeficiency virus or acquired immunodeficiency syndrome, autoimmune disease requiring systemic steroids in the past 2 years, or active pneumonitis.

The primary end point of the trial was to identify the maximum-tolerated dose of the regimen.

The median age of the 8 evaluable patients enrolled to the trial was 66 years, and the majority (n = 6) were male. Seventy-five percent entered the trial with stage III or IV disease, and 50% had stage IV disease. Moreover, initial tumor stages were II (n = 2), III and IIIB (n = 2), and IV (n = 4). All patients had the epithelioid and/or sarcomatoid disease variant.

Prior data on 4 evaluable male patients who received galinpepimut-S plus nivolumab for at least 1 month had been reported in June 2021.⁴ At this time point, the average OS with the regimen was 35.3 + 24.0 weeks, and the average PFS was 8.8 + 4.2 weeks, with a median PFS of 7 weeks in this population.

“This increase in survival appears to be consistent with long-term, immunity-mediated antitumor effect with this immunotherapy combination and it reinforces the data we unveiled earlier this year from the phase 1/2 clinical trial of galinpepimut-S in combination with another checkpoint inhibitor, pembrolizumab [Keytruda], in relapsed and refractory ovarian cancer patients, in which galinpepimut-S showed a superior disease control rate [DCR] compared to that seen with checkpoint inhibitors alone,” Stergiou added in the release.

The combination of galinpepimut-S and pembrolizumab was examined in patients with platinum-resistant, WT1-positive, relapsed/refractory advanced metastatic ovarian cancer, as part of another phase 1/2 trial (NCT03761914).⁵

Among 13 patients who were response evaluable, the overall response rate achieved with the doublet was 7.7%; this was noted to be comparable to what has been observed with checkpoint inhibitor monotherapy in this population. Moreover, with 43.1 weeks of follow-up, the median PFS was 12 weeks, and the median OS was not yet reached. The DCR with the regimen was 53.9%, according to findings from an ad-hoc analysis of those who responded to treatment.

“Of additional importance is the fact that both trials addressed patients with bulky disease, the setting in which other cancer vaccines have historically had very little effect,” Stergiou said. “We believe that the results of both studies demonstrate the potential effectiveness of galinpepimut-S as a combination therapy.”

References

1. SELLAS Life Sciences reports encouraging updated clinical data indicating increased survival from ongoing phase 1 mesothelioma study of galinpepimut-S combined with Opdivo. News release. SELLAS Life Sciences Group, Inc. June 8, 2022. Accessed June 14, 2022. https://bit.ly/3zxY22l
2. Galinpepimut-S (GPS) therapy. SELLAS Life Sciences Group, Inc. Accessed June 14, 2022. https://bit.ly/3jhZaPw
3. Using a targeted cancer vaccine (galinpepimut-S) with immunotherapy (nivolumab) in mesothelioma. ClinicalTrials.gov. Updated January 11, 2021. Accessed June 14, 2022. https://clinicaltrials.gov/ct2/show/NCT04040231
4. SELLAS reports encouraging updated clinical data from ongoing mesothelioma study of galinpepimut-S (GPS) combined with Opdivo. News release. SELLAS Life Sciences Group, Inc. June 24, 2021. Accessed June 14, 2022. https://bit.ly/3jm5Tb6
5. Sellas reports preliminary data showing clinical benefit from phase 1/2 clinical trial of galinpepimut-S (GPS) in combination with Keytruda in patients with WT1+ advanced ovarian cancer. News release. Sellas Life Sciences Group, Inc. May 26, 2022. Accessed June 14, 2022. bit.ly/3O2M0lJ