Pembrolizumab for Platinum-sensitive recurrent ovarian cancer

Inclusion criteria

• {"criterion_text":"- Signed and dated informed consent document for the study, willing and able to comply with protocol requirements, including: a.\tHLA-A2 phenotype determination by genetic test (blood) b.\tparticipation in translational research in HLA-A2 positive c.\tauthorization for long term follow up if HLA-A2 negative\n- 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)\n- Adequate organ function: •\t Adequate marrow function \tWhite blood cell (WBC) ≥3000/mm3 \tNeutrophils ≥1500/ mm3 \tPlatelets ≥ 100 × 103/mm3 (in the absence of transfusion within 2 weeks from before randomization) \tHaemoglobin ≥ 9 g/dL (in the absence of transfusion within 2 weeks from before randomization) •\tAdequate other organ functions \tALT and AST ≤ 2.5 × ULN, unless liver metastases are presents in which case they must be ≤ 5.0 × ULN \tTotal bilirubin ≤ 1.5× ULN (except Gilbert Syndrome: < 3.0 mg/dL) \tSerum creatinine ≤ 1.5 × ULN or creatinine clearance (CrCl) ≥ 40 mL/min (measured using the Cockcroft-Gault formula below): Female CrCl =\t(140 - age in years) × weight in kg × 0.85 72 × serum creatinine in mg/dL\n- Archival or fresh (if possible) tumor tissue must be available for evaluating relevant biomarkers.\n- 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\n- Stated willingness to comply with all study procedures and availability for the duration of the study\n- 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\n- Randomization must be within 8 weeks of the last dose of chemotherapy\n- Histologically proven non-mucinous epithelial ovarian cancer\n- Positive HLA-A2 phenotype\n- Age ≥ 18 years\n- ECOG Performance Status (PS) 0-1\n- 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\n- Previously treated with a PARP inhibitor or not eligible to PARPi (i.e ineligibility due to not complete or partial response to chemotherapy)\n- 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)"}

Exclusion criteria

• {"criterion_text":"- Patient with contra-indications to immune therapies\n- 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.\n- Immune-deficient status (patients with HIV, immunosuppressive treatment, haematological malignancies, and previous organ transplantation)\n- History of (non-infectious) pneumonitis/ interstitial lung disease that required steroids or has current pneumonitis / interstitial lung disease that requires steroids.\n- History of any chronic hepatitis as evidenced by: •\tPositive test for hepatitis B surface antigen •\tPositive test for qualitative hepatitis C viral load (by polymerase chain reaction [PCR])\n- Uncontrolled or significant cardiovascular disease including, but not limited to, any of the following: •\tMyocardial infarction or stroke/transient ischemic attack within the past 6 months •\tUncontrolled angina within the past 3 months •\tHistory 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) •\tAny history of clinically significant arrhythmias (such as ventricular tachycardia, ventricular fibrillation, or torsades de pointes) •\tQT interval corrected for heart rate using Fridericia’s formula (QTcF) prolongation > 480 msec •\tCardiovascular disease-related requirement for daily supplemental oxygen therapy\n- 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.\n- 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.\n- 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).\n- Patients who has an active infection requiring systemic therapy.\n- 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\n- Ongoing immunotherapy (checkpoint inhibition, antigen immunotherapy that would be scheduled to continue concomitantly to the study)\n- Any mental or psychiatric condition that, in the opinion of the investigator, is likely to compromise the ability to adhere to the protocol schedule\n- Life expectancy of less than 12 weeks\n- Pregnant or breastfeeding women\n- Concurrent participation in any other investigational study\n- Use of any of the following immunomodulatory agents within 30 days prior to the first dose of study drug: •\tSystemic 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 •\tInterferons •\tInterleukins •\tLive vaccine\n- Prior cancer vaccine therapy\n- Patient eligible for cytoreductive surgery at the time of inclusion\n- Patient with clinical, radiological or biological progression (according GCIG criteria) at the end of last chemotherapy\n- 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\n- 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\n- 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"}

Primary endpoints

• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time from randomization to progression assessed radiologically using RECIST 1.1 by the investigator, or death from any cause; patients alive and progression-free at cut-off are censored at last tumor assessment date."}

Secondary endpoints

• {"endpoint_text":"- 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 parti","definition_or_measurement_approach":"Objective response assessed by RECIST 1.1; best overall radiological response observed during treatment period before progression or subsequent anti-cancer therapy."}
• {"endpoint_text":"- Safety will be assessed based on NCI CTC-AE version 5.0","definition_or_measurement_approach":"Adverse events graded using NCI Common Terminology Criteria for Adverse Events (CTCAE) v5.0."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time from randomization to start of first subsequent anti-cancer treatment; deaths counted as events; censoring at last assessment if alive without subsequent treatment."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time from randomization to start of second subsequent anti-cancer treatment; deaths counted as events; censoring at last assessment if alive without second subsequent treatment."}
• {"endpoint_text":"- 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.","definition_or_measurement_approach":"Time from randomization to death from any cause; censoring at last known alive date for survivors."}

Belgium

Earliest CTIS Part Ii Submission Date

27-09-2024

Latest Decision Or Authorization Date

23-01-2026

Processing Time Days

483

Number Of Sites

3

Number Of Participants

16

France

Earliest CTIS Part Ii Submission Date

27-09-2024

Latest Decision Or Authorization Date

15-12-2025

Processing Time Days

444

Number Of Sites

31

Number Of Participants

134

Germany

Earliest CTIS Part Ii Submission Date

27-09-2024

Latest Decision Or Authorization Date

14-11-2024

Processing Time Days

413

Number Of Sites

6

Number Of Participants

30

Primary sponsor

Full Name

Asso De Recherche Cancers Gynecologiques

Organisation Type

Laboratory/Research/Testing facility

Country Of Registered Address

France

Third parties

• {"country":"","full_name":"Merck Sharp & Dohme LLC","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"OSE Immunotherapeutics","duties_or_roles":"Monetary support","organisation_type":""}