Combining a WT1 Vaccine (Galinpepimut-S) With Checkpoint Inhibition (Nivolumab) in Patients With WT1-Expressing
Prashasti Agrawal1,2, Michael Offin1,2, Victoria Lai1,2
1Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, 1275 York Avenue, New York City, NY, USA.
Introduction:
WT1 often presents on the surface of diffuse pleural mesotheliomas (DPMs) and is an ideal therapeutic target. Galinpepimut-S (GPS), a tetravalent, non-human leukocyte antigen-restricted, heteroclitic WT1-specific peptide vaccine was safe and effective in early phase clinical trials and upregulates T-cell suppressive programmed death-ligand 1 in the tumor microenvironment of other malignancies. A randomized phase 2 study of adjuvant GPS in patients with DPM trended toward improved median overall survival.
Methods:
To further enhance immunogenicity, we combined GPS with nivolumab, an anti-PD1 monoclonal antibody, in an open-label, single-center phase 1 study, examining tolerability and immunogenicity in patients with previously treated DPM. We enrolled patients with progressive or recurrent DPM treated with at least one course of pemetrexed-based chemotherapy. Patients received two doses of GPS followed by six doses of GPS with intravenous nivolumab every 2 weeks, and up to six additional cycles until disease progression or unacceptable toxicity.
Results:
Ten patients were treated; 70% experienced mostly mild treatment-related adverse events; two experienced a grade 3 or higher adverse event. Three of the 10 patients (30%) reported vaccine-specific T-cell responses. There were no partial responses; three patients had prolonged stable disease with up to 17% decrease in tumor volume. Median progression-free survival was 3.9 months and the median overall survival was 7.4 months.
Conclusions:
Coadministration of GPS and nivolumab reported a tolerable toxicity profile and induced immune responses in a subset of patients, but initial response and survival benefit were limited possibly owing to the small sample size.
Insights
This study combined a WT1 vaccine (GPS) with an anti-PD1 antibody (nivolumab) in mesothelioma patients. The combination was tolerable and induced immune responses, but showed limited survival benefit in this small phase 1 trial.
Area of Science:
- Oncology
- Immunotherapy
- Mesothelioma Research
Background:
- WT1 is a therapeutic target for diffuse pleural mesotheliomas (DPMs).
- Galinpepimut-S (GPS) is a WT1-specific peptide vaccine with demonstrated safety and efficacy in early trials.
- Previous studies suggest GPS can upregulate PD-L1 in the tumor microenvironment.
Purpose of the Study:
- To evaluate the tolerability and immunogenicity of combining GPS with nivolumab (anti-PD1) in patients with DPM.
- To assess the preliminary efficacy of this combination therapy.
Main Methods:
- An open-label, single-center phase 1 study.
- Enrolled patients with progressive or recurrent DPM previously treated with chemotherapy.
- Administered GPS followed by GPS with nivolumab intravenously every 2 weeks.
Main Results:
- Ten patients were treated; 70% experienced mild adverse events; 2 had grade 3+ events.
- Three patients (30%) showed vaccine-specific T-cell responses.
- Median progression-free survival was 3.9 months; median overall survival was 7.4 months; three patients had prolonged stable disease.
Conclusions:
- Coadministration of GPS and nivolumab demonstrated a tolerable toxicity profile.
- The combination induced immune responses in a subset of patients.
- Initial response and survival benefit were limited, potentially due to the small sample size.
