Recently, the clinical data on the treatment of two different types of WT1-positive (WT1+) advanced solid tumors with a new cancer vaccine galinpepimut-S (GPS) combined with immune checkpoint inhibitors were released. GPS is a cancer vaccine targeting WT1 (Wilms Tumor 1) protein. WT1 is one of the most widely expressed cancer antigens that is listed as the primary target of cancer immunotherapy by the National Cancer Institute of the United States.
The first study was a phase 1/2 “basket” study of GPS combined with anti-PD-1 therapy Keytruda (commonly known as pembrolizumab). The first group of evaluated patients (n=8) were diagnosed with second-or third-line WT1 (+) recurrent or refractory metastatic ovarian cancer. The first group of patients (n=8) were diagnosed with second-or third-line WT1 (+) recurrent or refractory metastatic ovarian cancer. Their median follow-up data showed that the disease control rate (DCR=ORR+ disease stability rate) of GPS+Keytruda combined therapy was 87.5%. In this group of refractory patients, 100% of them had no progress at the first evaluation time point, 6 weeks after the start of treatment. During the screening period, the positive rate of WT1 in ovarian cancer patients was about 70% by immunohistochemical (IHC) detection. Of the 8 assessable patients, 6 continued to receive GPS+Keytruda treatment. At present, the study is still recruiting patients, with a target of 20 patients in total. More mature clinical and immunobiological data are expected to be released by the end of the second quarter of 2021.
The second study was a phase 1 study sponsored by researchers of GPS combined with anti-PD-1 therapy Opdivo (commonly known as nivolumab) in patients with malignant pleural mesothelioma who relapsed after receiving first-to third-line standard therapy. The first group of assessable patients (n=3) had a median progression-free survival of at least 10 weeks after initiation of treatment. In patients with primary refractory MPM, any prolongation of PFS for more than 8 weeks is considered to be of clinical significance, considering the lack of effective treatment. All patients have an epithelioid variation of MPM, a tumor that generally expresses WT1. In addition, in this study, GPS was found to have appropriate immunogenicity, resulting in antigen (WT1)-specific CD4+T memory cell responses 3 months after the treatment started. Currently, the study is recruiting more MPM patients, and it is expected to complete by the end of the second quarter of 2021 (total number of target: 10) and publish more mature clinical and immunobiological data.
In these two studies, the safety of GPS in combination with checkpoint inhibitors was similar to that of checkpoint inhibitors alone, except that low-level, short-term local reactions were increased at the site where GPS was injected, which was consistent with previous GPS clinical studies.
GPS is a cancer vaccine targeting WT1 protein, which consists of four polypeptide chains and 25 epitopes. It can stimulate a strong immune response to the WT1 antigen. Combined with other therapies, it can kill the remaining tumor cells in the body during remission and strengthen the immune system’s immune monitoring of tumor cells. Prior to this, the FDA granted GPS a fast track approval to treat various cancers.
WT1 is one of the most widely expressed cancer antigens and listed as the primary target of cancer immunotherapy by the NCI. Importantly, as WT1 antigen is overexpressed in a variety of hematological malignant tumors and solid tumor cells, but not found in most normal tissues, GPS is expected to become a widely used immunotherapy for more than 20 different hematological malignant tumors and solid tumors.