Neo–Epitope-Based Vaccine Plus Pembrolizumab Under Exploration in Ovarian Cancer

The neo–epitope-based vaccine Tedopi (OSE2101) is under investigation either alone or in combination with pembrolizumab (Keytruda) as maintenance treatment vs best supportive care (BSC) in patients with recurrent ovarian cancer following platinum-based chemotherapy as part of the phase 2 TEDOVA trial (NCT04713514).¹

The vaccine is a proprietary combination of 9 optimized neo-epitopes plus 1 epitope giving universal T-cell response targeting T-cell activation.2 Tedopi is a specific T-cell–based immunotherapy that was designed to activate a cytotoxic T response that can eliminate cancer cells and restore immune surveillance of these cells in those with HLA-A2 positivity.

The multicenter, open-label, 3-arm phase 2 trial, which is sponsored and conducted by the French Oncology Cooperative Group ARCAGY-GINECO and supported by Merck Sharp & Dohme Corp. and OSE Immunotherapeutics, has enrolled its first patient.

“We are very pleased to announce enrollment of the first patient in TEDOVA, the first trial evaluating an innovative maintenance strategy for patients in first or second platinum-sensitive relapse post PARP inhibitor and bevacizumab [Avastin],” Alexandra Leary, MD, PhD, chief investigator of TEDOVA from Gustave Roussy Cancer Center, stated in a press release. “We look forward to evaluating this therapeutic option for women with ovarian cancer and a strong unmet medical need.”

For patients with ovarian cancer who present with either first or second platinum-sensitive relapse following bevacizumab and a PARP inhibitor, the only option is a platinum-based chemotherapy regimen for 6 cycles followed by observation. No FDA-approved options are available for use in the maintenance setting. As such, novel maintenance approaches are needed to prolong chemotherapy-free intervals in this population.

One strategy to turn “cold” ovarian cancer tumors into “hot” ones is through vaccination with tumor-associated or -specific epitopes that have been altered to increase major histocompatibility complex and T-cell receptor binding. The vaccine covers relevant tumor-associated antigens in the disease, including p53. It has been hypothesized that the vaccine plus an immune checkpoint inhibitor could successfully harness antitumor immunity.

To be eligible for enrollment to the phase 2 trial, patients needed to be 18 years of age or older, have histologically- or cytologically-proven non-mucinous epithelial ovarian cancer, a positive HLA-A2 phenotype, and an ECOG performance status of 0 or 1.3 Moreover, patients needed to have previously been treated with a PARP inhibitor and bevacizumab, acceptable organ function, and undergo randomization within 8 weeks of their last dose of platinum.

Patients who previously received treatment with immune checkpoint inhibitors, those with contraindications to immunotherapies, on ongoing immunotherapy, have previously received treatment with a cancer vaccine, or who were eligible for cytoreductive surgery at the time of inclusion, were excluded.

The trial is comprised of 3 arms. Those in arm A received BSC. Those in arm B received the vaccine by itself via subcutaneous injection on day 1 every 3 weeks for 7 doses and then every 6 weeks up to week 48 and then every 12 weeks until unacceptable toxicity, progressive disease, or up to 2 years. In arm C, patients received the vaccine at the same schedule as arm B plus intravenous pembrolizumab at a dose of 400 mg on day 1 every 6 weeks.

The primary outcome measure of the trial was progression-free survival, and key secondary outcome measures include objective response rate, incidence of treatment-emergent adverse effects, time to subsequent first and second treatments, and overall survival.

“Having the first patient enrolled by our oncology group partner marks a significant milestone in Tedopi’s development by exploring its impact in an additional oncology indication,” Alexis Peyroles, chief executive officer of OSE Immunotehrapeutics, stated in the press release. “We are expecting first results on the potential of such an innovative PD-1 targeted checkpoint combination strategy at the beginning of 2025.”

References

1. OSE Immunotherapeutics and ARCAGY-GINECO announce first patient randomized in phase 2 clinical trial evaluating Tedopi in combination with pembrolizumab in ovarian cancer. News release. OSE Immunotherapeutics. August 26, 2021. Accessed August 31, 2021. https://bit.ly/3jxGMSv
2. Research and Development. OSE Immunotherapeutics. Accessed August 31, 2021. https://bit.ly/3Dx1p9g
3. OSE2101 alone or in combination with pembrolizumab vs BSC in patient with platinum-sensitive recurrent OC (TEDOVA). ClinicalTrials.gov. Updated August 11, 2021. Accessed August 31, 2021. https://clinicaltrials.gov/ct2/show/NCT04713514