Galinpepimut-S Plus Nivolumab Shows Promising Preliminary Benefit in Mesothelioma

The combination of the targeted cancer vaccine galinpepimut-S (GPS) plus nivolumab (Opdivo) resulted in a median overall survival (OS) of 35.4 weeks in patients with macroscopic deposits of malignant pleural mesothelioma who had received treatment for at least 1 month, according to updated data from a phase 1 trial (NCT04040231).¹

At a median follow-up of 35.4 weeks, the average OS was 35.3 + 24.0 weeks. Moreover, the average progression-free survival (PFS) with the combination was 8.8 + 4.2 weeks, with a median PFS of 7 weeks in this population.

The toxicity profile of the combination was comparable with what has previously been experienced with single-agent nivolumab. However, low-grade, temporary local reactions have been reported at the galinpepimut-S injection site, which is consistent with what had been described in prior studies that have evaluated the vaccine.

“Considering the overall poor prognosis in this particular clinical setting, these preliminary data suggest that the combination of galinpepimut-S with the PD-1 inhibitor nivolumab may provide meaningful clinical benefit to patients with malignant pleural mesothelioma,” Angelos Stergiou, MD, ScDhc, president and chief executive officer at SELLAS Life Sciences Group, Inc., stated in a press release. “Surprisingly, the only [patient with] sarcomatoid mesothelioma enrolled, who was diagnosed with stage IV cancer, experienced a survival of 25 months and is still alive.”

Galinpepimut-S was designed to target malignancies that are characterized by an overexpression of the Wilms Tumor 1 (WT1) antigen.² SELLAS’ WT1 immunotherapy consists of 4 peptide chains and 2 of these are modified chains that elicit a strong, innate immune response against the WT1 antigen and access a broad range of human leukocyte antigen types.

When given to patients, the immune response induced by galinpepimut-S possesses the potential to identify and eliminate cancer cells and provide ongoing support and memory to the immune system so that it can continue to target and eliminate recurring disease and residual cancer cells. The vaccine is hypothesized to be a highly efficacious strategy for extending survival through the delaying and prevention of relapse or recurrence in patients who achieve complete remission or have minimal residual disease.

In the phase 1 trial, investigators set out to evaluate the safety of combining the vaccine with nivolumab in patients with mesothelioma.³ To be eligible to participate, patients needed to be aged 18 years or older, have a Karnofsky performance status of at least 70%, a pathologic diagnosis of malignant pleural mesothelioma, positive immunohistochemical staining for WT1 within 60 days of treatment initiation, have received at least 1 prior course of pemetrexed-based chemotherapy, and measurable disease.

If patients previously received checkpoint inhibitors, had 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, they were excluded.

All patients had the malignant pleural mesothelioma epithelioid and/or sarcomatoid variant, a tumor that universally expresses WT1, which is one of the most widely expressed cancer antigens. Moreover, participants had to have received and progressed on, or are refractory to, first-line treatment with pemetrexed-based chemotherapy. One patient had stage II disease, the second had stage IIB disease, and the third patient had stage IV disease.

The primary end point of the trial was to establish the maximum-tolerated dose of the regimen. A total of 4 male patients, aged approximately 67.3 + 4.1 (standard deviation), were given galinpepimut-S plus nivolumab for at least 1 month.

SELLAS announced that they will share more clinical and immune response data from the trial in Q4 2021; this will include an analysis of CD8+ and CD4+ T-cell responses to the WT1 peptide pool in the galinpepimut-S mixture. Investigators are also testing for antibody presence directed against the full-length WT1 protein, so data on epitope spreading will also become available in the future.

Investigators are also examining antibody presence against other important oncofetal antigens expressed in the disease, so data on inter-antigenic epitope spreading are also expected.

References

1. 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 28, 2021. https://bit.ly/3jm5Tb6
2. Galinpepimut-S (GPS) therapy. SELLAS Life Sciences Group, Inc. Accessed June 28, 2021. 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 28, 2021. https://clinicaltrials.gov/ct2/show/NCT04040231