First Patient Dosed in Phase 2 Study of Cancer Vaccine Combo in Ovarian Cancer

The first patient has been dosed in a Phase 2 extension study investigating the cancer vaccine DSP-7888 (ombipepimut-S) in combination with the checkpoint inhibitor Keytruda (pembrolizumab), in people with platinum-resistant ovarian cancer. The announcement follows promising data from the first portion of this Phase 1b/2 clinical trial (NCT03311334). The Phase 2 part is actively recruiting patients at sites across the United States. "Patients with platinum-resistant ovarian cancer have a high unmet need with limited treatment options; therefore, we are excited to advance the study of DSP-7888 plus pembrolizumab and evaluate its role and potential benefits," Patricia Andrews, said in a press release. Andrews is CEO and global head of oncology at Sumitomo Dainippon Pharma Oncology (SDP Oncology). Cancer patients are considered platinum-resistant if they do not respond to a specific type of chemotherapeutic agent that contains the chemical element of platinum. Cisplatin and carboplatin are two examples of regularly prescribed, platinum-containing chemotherapy medications. Patients who are platinum-resistant are typically resistant to other forms of chemotherapy, and also typically have worse clinical outcomes, with a median survival time of less than one year. In the search for a new line of treatment, researchers at SDP Oncology developed the DSP-7888 vaccine, which harnesses the body's immune system to attack cancer cells. Research has shown that certain types of cancer cells, including ovarian tumors, express the protein Wilms Tumor 1 (WT1) at high levels, allowing developers to use WT1 as a target to guide treatments. WT1 is considered the number-one target for cancer immunotherapy by the National Cancer Institute. The DSP-7888 vaccine consists of two peptide molecules (protein fragments) derived from the WT1 protein. When introduced in the body, these peptides trigger two cell types of the immune system, cytotoxic T-cells and helper T-cells, to target and attack the WT1 protein, and consequently, WT1-expressing cancer cells. There are several clinical studies investigating DSP-7888 as a treatment for different types of cancer, including the Phase 1b/2 clinical trial for that has now dosed its first patient in the Phase 2 portion. The initial, Phase 1b portion of the trial investigated the safety and tolerability of DSP-7888 in combination with Merck's immune checkpoint inhibitor Keytruda, an antibody treatment that blocks the activity of the PD-1 protein. (Merck is known as MSD outside the U.S. and Canada.) A second arm in this part of the trial assessed a combination of DSP-7888 plus another checkpoint inhibitor, Opdivo (nivolumab), that also targets the PD-1 molecule. PD-1 is involved with suppression of the immune response and, by blocking it, Keytruda and Opdivo are designed to enhance immune activity. The Phase 1b portion also allowed researchers to determine a recommended dose of DSP-7888 for future study, and the Phase 2 portion, also called a dose expansion study, will dose participants with the established dose, in combination with Keytruda. In total, 40 patients with platinum-resistant ovarian cancer will be enrolled initially in the Phase 2 study. Each patient will receive weekly DSP-7888, administered intradermally (in the skin) for the first six weeks, and subsequently every three weeks. Keytruda administration will begin on day one of the study, and it will be given every three-to-six weeks thereafter. The primary goal of the Phase 2 study is to evaluate the proportion of patients who show a significant tumor reduction after receiving the combination — a measure called objective response rate. The tumor reduction is considered significant if patients have either a complete response (CR) or a partial response (PR), with guidelines for responsiveness established by the Response Evaluation Criteria In Solid Tumors (RECIST) system. Secondary goals include duration of response (the time between response and disease progression), disease control rate (proportion of patients with at least stable disease), progression-free survival (the time patients live without signs of disease progression), and overall survival. Researchers also will use the iRECIST system, an adaptation of RECIST for agents that act on the immune system, to measure objective response rate, disease control rate, and progression free survival under the different guidelines. Ultimately, these measures are aimed at understanding the efficacy of the DSP-7888 vaccine, in combination with Keytruda, at modifying the immune system as a treatment for platinum-resistant ovarian cancer. "We look forward to better understanding how these combined mechanisms may be able to sensitize this patient population to immunomodulators and improve clinical benefits," said Andrews. SDP Oncology also is running one other Phase 2 clinical trial (NCT03149003) investigating DSP-7888, in combination with an immune checkpoint inhibitor, in patients with recurrent or progressive glioblastoma. The U.S. Food and Drug Administration has granted DSP-7888 orphan drug status for the indications of myelodysplastic syndromes (MDS) and brain cancer.