| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
1st or 2nd platinum-sensitive recurrent ovarian cancer with controlled disease after platinum based chemotherapy.
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| E.1.1.1 | Medical condition in easily understood language |
| Patient with platinum sensitive recurrent ovarian cancer |
| Patientinnen mit einem platin-sensitiven rezidivierenden Ovarialkarzinom (Eierstockkrebs) |
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| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 20.0 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10033128 |
| E.1.2 | Term | Ovarian cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 21.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10066697 |
| E.1.2 | Term | Ovarian cancer recurrent |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
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| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| To evaluate the benefit by the Progression Free Survival (PFS) according to RECIST 1.1 of maintenance OSE2101 alone or in combination with PD1 inhibition after platinum based chemotherapy in relapsed ovarian cancer. |
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| E.2.2 | Secondary objectives of the trial |
• To assess the Safety profile
• To determine the time to subsequent first treatment (TTST-1)
• To determine the time to subsequent second treatment (TTST-2)
• To assess Overall Survival (OS) |
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| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
1)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
2)Histologically proven non-mucinous epithelial ovarian cancer
3)Positive HLA-A2 phenotype
4)Age ≥ 18 years
5)ECOG Performance Status (PS) 0-1
6)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 to 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
7)Previously treated with a PARP inhibitor or not eligible to PARPi (i.e ineligibility due to not complete or partial response to chemotherapy)
8)Prior therapy with bevacizumab or with contra-indication to bevacizumab (i.e arterial thromboembolic events, history of intestinal perforation, any other contra-indications according to the SmPC)
9)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 the(as treatment or maintenance)
10)Randomization must be within 8 weeks of last dose of chemotherapy
11)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
12)Archival or fresh (if possible) tumor tissue must be available for evaluating relevant biomarkers.
13)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
14)Stated willingness to comply with all study procedures and availability for the duration of the study
15)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 |
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| E.4 | Principal exclusion criteria |
1)Patient with contra-indications to immune therapies
2)Ongoing immunotherapy (checkpoint inhibition, antigen immunotherapy that would be scheduled to continue concomitantly to the study)
3) Use of any following immunomodulatory agents in 30 days prior 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
•Life vaccine
4)Prior cancer vaccine therapy.
5)Patient eligible for cytoreductive surgery at the time of inclusion.
6)Patient with clinical, radiological or biological progression (according GCIG criteria) at the end of last chemotherapy.
7)Prior radiotherapy in 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.
8)Patient with active autoimmune disease that 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 allowed.
9)History of serious adverse reactions, including anaphylaxis and related symptoms as hives and respiratory difficulty following administration of any vaccines, or history of hypersensitivity, to any components of study vaccine
10)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.
11)Immune-deficient status (patients with HIV, immunosuppressive treatment, haematological malignancies, and previous organ transplantation)
12)History of (non-infectious) pneumonitis/ interstitial lung disease required steroids or has current pneumonitis/ interstitial lung disease that requires steroids.
13)History of any chronic hepatitis as evidenced by:
•Positive test for hepatitis B surface antigen
•Positive test for qualitative hepatitis C viral load by PCR
Note: Subjects with positive hepatitis C antibody and negative quantitative hepatitis C by PCR are eligible. History of resolved hepatitis A virus infection is not an exclusion criteria
14)Uncontrolled or significant cardiovascular disease including, but not limited to,any of the following:
•Myocardial infarction or stroke/transient ischemic attack in 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
15)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.
16)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 randomization.
17)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).
18)Patients who has an active infection requiring systemic therapy.
19)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
20)Any mental or psychiatric condition that in the opinion of the investigator, is likely to compromise the ability to adhere to protocol schedule
21)Life expectancy of less than 12 weeks
22)Pregnant or breastfeeding women
23)Concurrent participation in any other investigational study |
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| E.5 End points |
| E.5.1 | Primary end point(s) |
| Progression Free Survival (PFS) is the time from randomization to progression, assessed radiologically using RECIST 1.1 by the investigator, or death whatever the cause, whichever comes first. Patients alive and free of progression at the cut-off date will be censored at the last tumor assessment date. |
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| E.5.1.1 | Timepoint(s) of evaluation of this end point |
date of disease progression according RESIST 1.1 of last patient (Event driven trial)
Estimated date Q4 2025 |
|
| E.5.2 | Secondary end point(s) |
•Objective response is defined using the RECIST 1.1. The best overall response is defined as the best radiological response observed over the whole treatment period before progression or subsequent anti-cancer treatment. Proportion of partial and complete responses over the treated population will be computed.
•Safety will be assessed based on NCI CTC-AE version 5.0
•Time to subsequent first treatment (TTST-1) is defined as time from randomization to initiation of first subsequent treatment (including treatment change due to toxicity or investigator’s decision). Deaths will be counted as events. Patients alive and not receiving a subsequent treatment will be censored at the last assessment date.
•Time to subsequent second treatment (TTST-2) is defined as time from randomization to initiation of second subsequent treatment (including treatment change due to toxicity or investigator’s decision). Deaths will be counted as events. Patients alive and not receiving a subsequent treatment will be censored at the last assessment date.
•Overall survival is defined as time from randomization to the date of death, whatever the cause. Patients alive at the cut-off date will be censored at the last date they are known to be alive.
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| E.5.2.1 | Timepoint(s) of evaluation of this end point |
| Same as primary end point: estimated date Q4 2025 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | Yes |
| E.6.13.1 | Other scope of the trial description |
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| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 3 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 7 |
| E.8.5 | The trial involves multiple Member States | Yes |
| E.8.5.1 | Number of sites anticipated in the EEA | 35 |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
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| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 4 |
| E.8.9.1 | In the Member State concerned months | 6 |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 4 |
| E.8.9.2 | In all countries concerned by the trial months | 6 |
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