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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Asso De Recherche Cancers Gynecologiques

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

5 Aug 2021 → ongoing

Decision date (initial)

2024-10-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Merck Sharp & Dohme LLC · OSE Immunotherapeutics

External identifiers

EU CT number

2024-516096-32-00

EudraCT number

2020-004364-25

ClinicalTrials.gov

NCT04713514

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Others, Therapy

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 objectives 5

1. To compare the best Overall Response Rate for patients with measurable disease at randomization using RECIST1.1
2. To assess the Safety profile
3. To determine the time to subsequent first treatment (TTST-1)
4. To determine the time to subsequent second treatment (TTST-2)
5. To assess Overall Survival (OS)

Conditions and MedDRA coding

Platinum sensitive recurrent ovarian cancer

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 15

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. Randomization must be within 8 weeks of the last dose of chemotherapy
3. Histologically proven non-mucinous epithelial ovarian cancer
4. Positive HLA-A2 phenotype
5. Age ≥ 18 years
6. ECOG Performance Status (PS) 0-1
7. 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
8. Previously treated with a PARP inhibitor or not eligible to PARPi (i.e ineligibility due to not complete or partial response to chemotherapy)
9. 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)
10. 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)
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

Exclusion criteria 23

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 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
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 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
8. 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
9. 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
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 that 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 polymerase chain reaction [PCR])
14. 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
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 date of 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 the protocol schedule
21. Life expectancy of less than 12 weeks
22. Pregnant or breastfeeding women
23. Concurrent participation in any other investigational study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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.

Secondary endpoints 5

1. 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
2. Safety will be assessed based on NCI CTC-AE version 5.0
3. 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.
4. 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.
5. 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.

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Asso De Recherche Cancers Gynecologiques

Sponsor organisation

Asso De Recherche Cancers Gynecologiques

Address

8 Rue Lamennais

City

Paris

Postcode

75008

Country

France

Scientific contact point

Organisation

Asso De Recherche Cancers Gynecologiques

Contact name

Alexandra LEARY

Public contact point

Organisation

Asso De Recherche Cancers Gynecologiques

Contact name

Alexandra LEARY

Locations

3 EU/EEA countries · 40 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 29 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications