Phase II Randomized Study of OSE2101 and Pembrolizumab Versus Supportive Care in Platinum-Sensitive Recurrent Ovarian Cancer Post-Chemotherapy
- Trial ID
- 2024-516096-32-00
- Protocol
- GINECO-OV244b
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this randomized Phase II study is to evaluate the benefit of maintenance therapy with **OSE2101** alone or in combination with **PD1** inhibition, specifically **pembrolizumab**, in patients with platinum-sensitive recurrent ovarian cancer. The evaluation is based on **Progression Free Survival (PFS)** according to **RECIST 1.1** criteria following platinum-based chemotherapy. This is clinically relevant as it aims to determine the efficacy of these maintenance therapies in prolonging the time patients remain free from disease progression, which is a critical factor in the management of recurrent ovarian cancer.
The secondary objectives include:
- Comparing the best **Overall Response Rate** for patients with measurable disease at randomization using **RECIST 1.1**.
- Assessing the **Safety** profile of the treatments.
- Determining the time to subsequent first treatment (**TTST-1**).
- Determining the time to subsequent second treatment (**TTST-2**).
- Assessing **Overall Survival (OS)**.
Participants
The clinical trial focuses on **platinum-sensitive recurrent ovarian cancer** and involves a study population exclusively composed of female participants. The age range of the participants is 18 years and older, with no upper age limit specified. The trial does not include a vulnerable population. Participants were selected based on specific criteria, including a positive HLA-A2 phenotype and a history of non-mucinous epithelial ovarian cancer. The trial population is required to have an Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1, indicating they are fully active or restricted in physically strenuous activity but ambulatory. Participants must have experienced a clinical or radiological relapse of platinum-sensitive ovarian cancer, having received at least four infusions of platinum during their last line of chemotherapy. The sponsor has not provided the total number of participants involved in the study. Lifestyle considerations such as diet and physical activity are not specified, but participants must comply with study procedures and be available for the study duration. Key inclusion criteria include adequate organ function and a willingness to use effective contraception if of childbearing potential. The trial does not include male subjects, and no information is provided regarding the participants' general health status beyond the specified criteria.
Plans and Procedures
The clinical trial is designed as a **randomized**, **double-blind**, controlled study to evaluate the efficacy of two maintenance therapies, OSE2101 (TEDOPI) alone or in combination with **pembrolizumab**, compared to best supportive care in patients with platinum-sensitive recurrent ovarian cancer. The trial aims to assess the benefit of these therapies by measuring **Progression Free Survival (PFS)** according to RECIST 1.1 criteria. The study is expected to run until December 31, 2025, with recruitment having commenced on August 5, 2021.
Participants will undergo a series of study visits, beginning with an inclusion (screening) visit to determine eligibility based on criteria such as HLA-A2 phenotype, adequate organ function, and a history of platinum-sensitive ovarian cancer. Following randomization, participants will receive treatment and attend regular follow-up visits to monitor safety and efficacy, including assessments of tumor response and adverse events. The end-of-study visit will conclude the participant's involvement, with data collected on overall survival and time to subsequent treatments.
The expected duration of participant involvement is up to 24 months, contingent on the absence of disease progression or unacceptable toxicity. Conditions that may lead to early termination from the study include significant adverse reactions, withdrawal of consent, or any medical condition that, in the investigator's opinion, would compromise the participant's safety or the integrity of the study data. The trial's primary endpoint is the time from randomization to disease progression or death, while secondary endpoints include objective response rate, safety assessments, and overall survival.
Treatment
The clinical trial involves the administration of **KEYTRUDA** (pembrolizumab), a concentrate for solution for infusion, as one of the experimental medications. KEYTRUDA is provided in a concentration of 25 mg/mL and is administered via **intravenous infusion**. The maximum daily dose is 400 mg, with a total maximum dose of 7200 mg over a treatment period of up to 24 months. Pembrolizumab is a protein-based therapeutic agent, specifically classified under the ATC code L01FF02. The administration schedule and participant compliance are monitored to ensure adherence to the dosing regimen.
Another experimental treatment in the study is **TEDOPI**, an emulsion for injection, which is administered via **subcutaneous injection**. TEDOPI contains multiple active substances, including MPS-112, MPS-106, MPS-213, MPS-102, MPS-216, MPS-103, MPS-215, MPS-214, D-ALA-LYS-CHA-VAL-ALA-ALA-TRP-THR-LEU-LYS-ALA-ALA-D-ALA, and MPS-200. The maximum daily dose for TEDOPI is 5 mg, with a total maximum dose of 85 mg over a treatment period of up to 24 months. TEDOPI is categorized as a cancer vaccine and is composed of protein-based substances. The administration schedule is designed to optimize therapeutic outcomes, and participant compliance is closely monitored throughout the trial.
The trial does not include any non-experimental treatments such as standard-of-care therapy, placebo, or comparator treatment. The focus is on evaluating the efficacy of the experimental treatments, KEYTRUDA and TEDOPI, either alone or in combination, in the context of maintenance therapy for platinum-sensitive recurrent ovarian cancer. The study protocol ensures rigorous monitoring of drug administration and participant adherence to the prescribed dosing schedules.
Efficacy
The efficacy of the clinical trial will be assessed primarily through **Progression Free Survival (PFS)**, which is defined as the time from randomization to disease progression, as assessed radiologically using RECIST 1.1 criteria by the investigator, or death from any cause, whichever occurs first. Patients who are alive and free of progression at the cut-off date will be censored at the last tumor assessment date. Secondary endpoints include objective response, safety assessed based on NCI CTC-AE version 5.0, time to subsequent first treatment (TTST-1), time to subsequent second treatment (TTST-2), and overall survival. Objective response is defined using RECIST 1.1, with the best overall response being the best radiological response observed over the entire treatment period before progression or subsequent anti-cancer treatment. Overall survival is defined as the time from randomization to the date of death from any cause, with patients alive at the cut-off date being censored at the last date they are known to be alive.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Signed and dated informed consent document for the study, willing and able to comply with protocol requirements, including: a. HLA-A2 phenotype determination by genetic test (blood) b. participation in translational research in HLA-A2 positive c. authorization for long term follow up if HLA-A2 negative
- Randomization must be within 8 weeks of the last dose of chemotherapy
- Histologically proven non-mucinous epithelial ovarian cancer
- Positive HLA-A2 phenotype
- Age ≥ 18 years
- ECOG Performance Status (PS) 0-1
- Clinical or radiological relapse of a platinum sensitive ovarian cancer regardless of the number of prior lines of platinum-based chemotherapy, as long as each prior line fulfilled the platinum sensitive criteria defined as complete response, partial response or stable disease according RECIST 1.1 at the end of a platinum-based chemotherapy. Patient must have received at least 4 infusions of platinum during the last line of platinum-based chemotherapy
- Previously treated with a PARP inhibitor or not eligible to PARPi (i.e ineligibility due to not complete or partial response to chemotherapy)
- Prior therapy with bevacizumab or with contra-indication to bevacizumab (i.e arterial thromboembolic events, history of intestinal perforation, any other contra-indication according the SmPC)
- Patient may have received prior immune checkpoint inhibitor (ICI), such as anti-PD-(L)1 or anti-CTLA-4 antibody and had a relapse after receiving the ICI without concomitant chemotherapy for at least 6 months (as treatment or maintenance)
- Adequate organ function: • Adequate marrow function White blood cell (WBC) ≥3000/mm3 Neutrophils ≥1500/ mm3 Platelets ≥ 100 × 103/mm3 (in the absence of transfusion within 2 weeks from before randomization) Haemoglobin ≥ 9 g/dL (in the absence of transfusion within 2 weeks from before randomization) • Adequate other organ functions ALT and AST ≤ 2.5 × ULN, unless liver metastases are presents in which case they must be ≤ 5.0 × ULN Total bilirubin ≤ 1.5× ULN (except Gilbert Syndrome: < 3.0 mg/dL) Serum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 40 mL/min (measured using the Cockcroft-Gault formula below): Female CrCl = (140 - age in years) × weight in kg × 0.85 72 × serum creatinine in mg/dL
- Archival or fresh (if possible) tumor tissue must be available for evaluating relevant biomarkers.
- Women of childbearing potential must have a negative serum or urine pregnancy test within 72 hours prior to treatment allocation, and have to use of highly effective contraception during the treatment period and for at least 180 days after the last dose of study treatment
- Stated willingness to comply with all study procedures and availability for the duration of the study
- For countries where this will apply to : a subject will be eligible for randomization in this study only if either affiliated to, or a beneficiary of, a social security category
Exclusion Criteria
- Patient with contra-indications to immune therapies
- Ongoing immunotherapy (checkpoint inhibition, antigen immunotherapy that would be scheduled to continue concomitantly to the study)
- Use of any of the following immunomodulatory agents within 30 days prior to the first dose of study drug: • Systemic corticosteroids (at dose higher than 10 mg/day equivalent prednisone); if systemic corticoid use, corticoid must be stopped at least 7 days before study treatment start • Interferons • Interleukins • Live vaccine
- Prior cancer vaccine therapy
- Patient eligible for cytoreductive surgery at the time of inclusion
- Patient with clinical, radiological or biological progression (according GCIG criteria) at the end of last chemotherapy
- Prior radiotherapy within 2 weeks of start of study intervention. Participants must have recovered from all radiation-related toxicities, not require corticosteroids, and not have had radiation pneumonitis. A 1-week washout is permitted for palliative radiation (≤2 weeks of radiotherapy) to non-CNS disease
- Patient with active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed
- History of serious adverse reactions, including anaphylaxis and related symptoms such as hives and respiratory difficulty following administration of any vaccines, or a history of hypersensitivity, specifically to any components of study vaccine
- Prior history of other malignancies other than study disease (except for basal cell or squamous cell carcinoma of the skin or carcinoma in situ of the cervix or other in situ cancer considered as cured) unless the patient has been free of the disease for at least 5 years.
- Immune-deficient status (patients with HIV, immunosuppressive treatment, haematological malignancies, and previous organ transplantation)
- History of (non-infectious) pneumonitis/ interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease that requires steroids.
- History of any chronic hepatitis as evidenced by: • Positive test for hepatitis B surface antigen • Positive test for qualitative hepatitis C viral load (by polymerase chain reaction [PCR])
- Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: • Myocardial infarction or stroke/transient ischemic attack within the past 6 months • Uncontrolled angina within the past 3 months • History of other clinically significant heart disease (eg, cardiomyopathy, congestive heart failure with New York Heart Association functional classification III-IV, pericarditis, significant pericardial effusion, or myocarditis) • Any history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes) • QT interval corrected for heart rate using Fridericia’s formula (QTcF) prolongation > 480 msec • Cardiovascular disease-related requirement for daily supplemental oxygen therapy
- Subjects with known or suspected CNS metastases, untreated CNS metastases, are excluded. However, subjects with controlled brain metastases will be allowed to enroll. Controlled brain metastases are defined as no radiographic progression for at least 4 weeks following radiation and/or surgical treatment (or 4 weeks of observation if no intervention is clinically indicated), and off of steroids for at least 2 weeks, and no new or progressive neurological signs and symptoms.
- Any major surgery within 4 weeks of study drug administration. Subjects must have recovered from the effects of major surgery or significant traumatic injury at least 14 days before date of randomization.
- Patients who has severe hypersensitivity (Grade 3 or higher) to pembrolizumab and/or any of its excipients (refer to the IB for a list of excipients).
- Patients who has an active infection requiring systemic therapy.
- Any acute medical condition that in the opinion of the investigator may obscure the ability to observe the safety or activity of the study vaccine treatment
- Any mental or psychiatric condition that, in the opinion of the investigator, is likely to compromise the ability to adhere to the protocol schedule
- Life expectancy of less than 12 weeks
- Pregnant or breastfeeding women
- Concurrent participation in any other investigational study
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Belgium | Not Recruiting | 05 Aug 2021 | 16 |
 France | Not Recruiting | 05 Aug 2021 | 134 |
 Germany | Not Recruiting | 05 Aug 2021 | 30 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
TEDOPI | Test | EMULSION FOR INJECTION | SUBCUTANEOUS INJECTION | 5 | 24 | PRD11292393 |
KEYTRUDA 25 mg/mL concentrate for solution for infusion | Test | CONCENTRATE FOR SOLUTION FOR INFUSION | INTRAVENIOUS INFUSION | 400 | 24 | PRD4323105 |