Novel Cancer Vaccine DSP-7888 Proceeds to Phase 2 in Ovarian Cancer, First Patient Dosed

The novel immunotherapeutic vaccine DSP-7888 (ombipepimut-S or adegramotide/nelatimotide), in combination with pembrolizumab (Keytruda), has been dosed in the first patient with platinum-resistant ovarian cancer, according to Sumitomo Dainippon Pharma Oncology, Inc., the developer of the agent.¹

DSP-7888 is being evaluated in a phase 1b/2 open-label (NCT03311334), multicenter study; the patient was dosed in the phase 2 expansion portion.

“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,” said Patricia S. Andrews, chief executive officer and global head of oncology at Sumitomo Dainippon Pharma Oncology. “Furthermore, we look forward to better understanding how these combined mechanisms may be able to sensitize this patient population to immunomodulators and improve clinical benefits.”

The anti-cancer vaccine targets the Wilms Tumor 1 (WT1) protein, which is overexpressed in many ovarian cancers. DSP-7888 contains 2 peptides that induce WT1-specific cytotoxic T lymphocytes and helper T cells to attack WT1-expressive cancer cells.

In the phase 1b portion of the trial, patients with solid tumors were evaluated for safety and tolerability with DSP-7888 and a PD-1 checkpoint inhibitor (nivolumab [Opdivo] or pembrolizumab).2 Patients with neoplasms, melanoma, non–small cell lung cancer, head and neck squamous cell carcinoma, renal cell carcinoma, urothelial neoplasm, hepatocellular carcinoma, microsatellite instability–high or mismatch repair deficient tumors, colorectal cancer, gastroesophageal junction adenocarcinoma, gastric cancer, cervical cancer, primary peritoneal cancer, platinum-resistant ovarian cancer, serous epithelial ovarian cancer, and fallopian tube cancer were included in the phase 1b portion of the study.

Based on findings from the phase 1b portion, as well as the prevalence of WT1 in patients with ovarian cancer, the phase 2 portion of the study was initiated.¹

The phase 2 portion will evaluate the preliminary antitumor activity of a dosing emulsion administration of the vaccine plus pembrolizumab with regard to overall response rate (ORR). Patients may be treated for up to 24 months.²

Secondary end points include duration of response (DOR), disease control rate (DCR), progression-free survival (PFS), 6-month PFS, overall survival up to 48 months, immune ORR, immune DCR, immune PFS, immune DOR, and safety.

The dosing emulsion administration will be given intradermally DSP-7888 every 7 days until cycle 2 and every 21 days in combination with pembrolizumab.

In addition to having platinum-resistant ovarian cancer, patients have to be positive for at least 1 of these human leukocyte antigens (HLA): HLA-A*02:01, HLA-A*02:06, HLA-A*24:02, HLA-A*03:01, or HLA-B*15:01. Patients also have to be considered platinum resistant to last administered platinum-based therapy, defined as relapse within 6 months after last dose of platinum-based therapy, and have completed at least 1 but no more than 4 prior lines of therapy for serous epithelial ovarian, fallopian tube, or primary peritoneal cancer. Additional inclusion criteria are defined in the study.

Key exclusion criteria include patients with primary platinum-refractory disease, patients with known, untreated brain metastases, patients who received prior treatment with other PD-1/PD-L1 inhibitors or immuno-regulatory receptor inhibitors, such as anti–CTLA-4, LAG-3, IL-2R, or GITR antibodies, patients who have received certain treatments for ovarian cancer within prespecified time frames, patients who have received a live vaccine within 4 weeks prior to first dose of DSP-7888, and patients with any known additional, progressive malignancy that required active treatment, with certain exceptions. Additional exclusion criteria are defined in the study.

The trial is currently recruiting, and the estimated enrollment is 104 patients.

References

1. Sumitomo Dainippon Pharma Oncology announces first patient dosed in phase 2 dose-expansion portion of study evaluating investigational WT1 immunotherapeutic cancer vaccine DSP-7888 (ombipepimut-S*) in patients with ovarian cancer. News release. October 27, 2020. Accessed November 25, 2020. https://prn.to/3lA0zi1
2. A study of DSP-7888 dosing emulsion in combination with immune checkpoint inhibitors in adult patients with advanced solid tumors. ClinicalTrials.gov. November 2, 2020. Accessed November 25, 2020. https://bit.ly/3mqWKNj