Evaluation of two maintenance therapies (OSE2101 alone or in combination with pembrolizumab) versus best supportive care in patient with platinum-sensitive recurrent ovarian cancer

Phase 1

• Conditions: 1st or 2nd platinum-sensitive recurrent ovarian cancer with controlled disease after platinum based chemotherapy.; MedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); MedDRA version: 21.1Level: PTClassification code 10066697Term: Ovarian cancer recurrentSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2020-004364-25-DE
• Lead Sponsor: ARCAGY-GINECO

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-12-02
• Last Update Posted: 26 August 2024

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 180

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
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

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 metasta

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: 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. ;Secondary Objective: • To assess the Safety profile<br>• To determine the time to subsequent first treatment (TTST-1)<br>• To determine the time to subsequent second treatment (TTST-2)<br>• To assess Overall Survival (OS);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.;Timepoint(s) of evaluation of this end point: date of disease progression according RESIST 1.1 of last patient (Event driven trial)<br>Estimated date Q4 2025