TEDOVA: vaccine OSE2101 +/- pembrolizumab as maintenance in platinum-sensitive recurrent ovarian cancer: clinical trial protocol
Ovarian cancer is a leading cause of death from gynecological cancers worldwide. Platinum-based chemotherapy provides the cornerstone of the medical management. In first line and subsequent relapses, maintenance strategies are offered to prolong intervals between lines of chemotherapy. Current maint...
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| Main Authors: | , , , , , , , , , , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
2024
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| In: |
Future oncology
Year: 2024, Pages: 1-10 |
| ISSN: | 1744-8301 |
| DOI: | 10.1080/14796694.2024.2386922 |
| Online Access: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1080/14796694.2024.2386922
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| Author Notes: | Rayan Kabirian, Olivier Tredan, Frederik Marmé, Xavier Paoletti, Lauriane Eberst, Coriolan Lebreton, Thibault De La Motte Rouge, Renaud Sabatier, Antoine Angelergues, Michel Fabbro, Toon Van Gorp, Laura Mansi, Laurence Gladieff, Emilie Kaczmarek, Jérôme Alexandre, Thomas Grellety, Laure Favier, Julia Welz, Jean-Sébastien Frenel and Alexandra Leary |
| Summary: | Ovarian cancer is a leading cause of death from gynecological cancers worldwide. Platinum-based chemotherapy provides the cornerstone of the medical management. In first line and subsequent relapses, maintenance strategies are offered to prolong intervals between lines of chemotherapy. Current maintenance options involve bevacizumab and poly ADP-ribose polymerase inhibitors, but these lines of therapy can only be used once in the disease course. Patients in first or second platinum sensitive relapse after poly ADP-ribose polymerase inhibitors and bevacizumab represent an area of unmet medical need. This academic sponsored, international Phase II randomized trial is evaluating the combination of a therapeutic cancer vaccine (OSE2101) with anti-PD1 (pembrolizumab) as maintenance therapy, in patients with platinum-sensitive recurrence regardless of number of prior lines and no progression after platinum-based chemotherapy. Clinical Trial Registration: NCT04713514 (ClinicalTrials.gov) Ongoing Phase II study randomizing vaccine OSE2101 +/- Pembrolizumab vs supportive care as maintenance in platinum-sensitive recurrent ovarian cancer. Phase II study evaluating vaccine OSE2101 +/- Pembrolizumab vs supportive care as maintenance in patients with recurrent platinum-sensitive ovarian cancer. Ovarian cancer often becomes a long-term condition that needs ongoing treatment. After chemotherapy, women usually receive additional treatments to keep the cancer under control. There are only two approved treatments for this: bevacizumab administered every 3 weeks, and poly ADP-ribose polymerase inhibitors (PARP) inhibitors, which are pills that women can take if their cancer responds to platinum-based chemotherapy. However, if women have already been treated with both bevacizumab and a PARP inhibitor, there are no approved options left to maintain control of the cancer after chemotherapy. A new potential treatment, called OSE2101, is being studied: it is a vaccine designed to activate the body’s immune cells to fight against cancer. The TEDOVA study is looking at how well this vaccine works in women with ovarian cancer who have already been treated with both bevacizumab and a PARP inhibitor and whose cancer is responding to platinum-based chemotherapy again. Participants are randomly assigned to one of three groups after their chemotherapy: standard supportive care, OSE2101 vaccine alone and the combination of OSE2101 vaccine with pembrolizumab. The goal of the TEDOVA study is to see if the combination of the OSE2101 vaccine and pembrolizumab can better control the cancer and to make sure the treatments are safe. The study is being run by ARCAGY-GINECO and is currently recruiting patients in France, Germany and Belgium. The study will continue to accept new patients until the end of 2024, and it is registered on ClinicalTrial.gov under the number NCT04713514. Most patients diagnosed with ovarian cancer (OC) have no evidence of disease after standard treatment with debulking surgery and platinum-based chemotherapy. Long-term survival depends on the recurrence of the disease, the delay between the last platinum-based chemotherapy defining the platinum-sensibility which is a major prognostic factor. Women with platinum-sensible relapse (more than 6 months after the last platinum received) will be managed as patients with a chronic disease requiring iterative lines of platinum-based chemotherapy. After several cycles of treatment, chemotherapy is usually stopped and one of the major priorities is to extend platinum-free interval proposing maintenance strategies, as targeted therapy bevacizumab or poly ADP-ribose polymerase inhibitors (PARPi). When those lines of therapy have been received during previously, they cannot be reuse. That is the reason of developing new therapies and associations as maintenance therapy. TEDOVA is a Phase II, randomized, open-label, multicenter study assessing the efficacy of vaccine OSE2101 + anti PD-1 pembrolizumab as maintenance therapy in women with platinum-sensible relapse of OC. We included women with HLA-A2 phenotype ( 45% of the general population) with platinum sensitive OC regardless of the number of prior lines of platinum-based chemotherapy. Patients must have been previously treated with bevacizumab and a PARPi, or have a contra-indication. The primary end point is to evaluate the progression free survival of maintenance OSE2101 alone or in combination with PD1 inhibitor. The secondary end points are to compare the best overall response rate for patients with measurable disease at randomization, the safety and tolerability, the time to subsequent first and second treatments and the overall survival. Eligible patients were aged ≥18 years of age with histologically proven non-mucinous epithelial OC, positive HLA-A2 phenotype, and platinum sensitive OC regardless of the number of prior lines of platinum-based chemotherapy. Patients must have been previously treated with bevacizumab and a PARPi, or have a contraindication. A total of 180 patients with an HLA-A2 positive phenotype will be randomized into three study arms in a 1:1:2 ratio: Arm A (n = 45) will receive observation/best supportive care, Arm B (n = 45) will receive OSE2101 and Arm C (n = 90) will receive OSE2101 plus pembrolizumab. Patients will be followed until disease progression, intolerance, withdrawal of consent, or for up to 2 years. One-sided log-rank tests will be conducted in a predefined sequence:○ H1: Compare Arm C (OSE2101 + pembrolizumab) with Arm A (best supportive care).○ If H1 shows a statistically significant difference, then proceed to:○ H2: Compare Arm C (OSE2101 + pembrolizumab) with Arm B (OSE2101).○ If both H1 and H2 show statistically significant differences, then proceed to:○ H3: Compare Arm B (OSE2101) with Arm A (best supportive care).○ A total of 121 events (progressions or deaths) is required to perform the first test of H1. H1: Compare Arm C (OSE2101 + pembrolizumab) with Arm A (best supportive care). If H1 shows a statistically significant difference, then proceed to: H2: Compare Arm C (OSE2101 + pembrolizumab) with Arm B (OSE2101). If both H1 and H2 show statistically significant differences, then proceed to: H3: Compare Arm B (OSE2101) with Arm A (best supportive care). A total of 121 events (progressions or deaths) is required to perform the first test of H1. |
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| Item Description: | Online veröffentlicht: 19. August 2024 Im Titel sind bei "OSE2101 +/- pembrolizumab" das Plus- und Minussymbol dargestellt Gesehen am 04.11.2024 |
| Physical Description: | Online Resource |
| ISSN: | 1744-8301 |
| DOI: | 10.1080/14796694.2024.2386922 |