OSE2101 Alone or in Combination With Pembrolizumab vs BSC in Patient With Platinum-sensitive Recurrent OC

NCT04713514 | Active Not Recruiting Phase 2 DMC

• 3 other identifiers: GINECO-OV244b2020-004364-25ENGOT-ov58
• Study Type: interventional
• Target: 180
• Locations: 3 countries
• Sites: 40

Brief Summary

The proposed study is an international randomized phase II, multicenter, open-label, three arms trial to assess best supportive care (BSC) vs OSE2101 and vs OSE2101 + pembrolizumab as maintenance treatment for patients with platinum sensitive relapsed ovarian cancers, previously treated with chemotherapy (regardless of the number of prior lines of platinum-based chemotherapy), bevacizumab (if eligible) and a PARP inhibitor (if eligible). Patients in Complete Response, Partial Response, or Stable Disease at the end of chemotherapy with at least 4 cycles of platinum based chemotherapy will be randomized in one of the three arms (randomization 1:1:2). They will receive one or the two study treatments or BSC until progression, or intolerance, or up to 2 years (from 1st study treatment dose).

Conditions

Platinum-sensitive Ovarian Cancer; Relapsed Ovarian Cancer

Keywords

Maintenance therapy; Immunotherapy; Cancer vaccine; Cold tumor; Relapse; Pembrolizumab; TEDOPI

Outcome Measures

Primary Outcomes (1)

• Progression free survival (PFS)

  Progression-free survival (PFS) is the time from randomization to progression measured radiologically using RECIST v1.1 guidelines as reported 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

  from date to randomization to date of event, assessed up to 4 years

Secondary Outcomes (5)

• Objective response rate (ORR)

  from date to randomization to date of event, assessed up to 4 years

• Incidence of treatment emergent adverse events

  from date to randomization to date of study end, assessed up to 4 years

• Time to subsequent first treatments (TTST-1)

  from date to randomization to date of event, assessed up to 4 years

• Time to subsequent second treatments (TTST-2)

  from date to randomization to date of event, assessed up to 4 years

• Overall Survival (OS)

  from date to randomization to death from any cause, assessed up to 4 years

Study Arms (3)

Arm A : Best Supportive Care

NO INTERVENTION

Observational arm (Standard of care)

Arm B : OSE2101

EXPERIMENTAL

OSE2101 monotherapy - subcutaneous injection on day 1, every 3 weeks for 7 doses then every 6 weeks up to week 48 and then every 12 weeks until intolerance, disease progression, or up to 2 years. OSE2101 vaccine is an emulsion of peptides suspension in in Montanide® ISA 51 adjuvant and containing 0.5 mg/mL of each 10 synthetically manufactured peptides (5.0 mg/mL total peptide) in 1.5 mL of emulsion.

Drug: OSE2101

Arm C : OSE2101 + Pembrolizumab

EXPERIMENTAL

OSE2101 (subcutaneous injection on day 1, every 3 weeks for 7 doses then every 6 weeks up to week 48 and then every 12 weeks until intolerance, disease progression, or up to 2 years) + pembrolizumab (400 mg IV infusion on day 1 every 6 weeks until intolerance, disease progression, or up to 2 years.

Drug: OSE2101; Drug: Pembrolizumab 25 MG/ML [Keytruda]

Interventions

OSE2101 DRUG

subcutaneous injection on day 1, every 3 weeks for 7 doses then every 6 weeks up to week 48 and then every 12 weeks until intolerance, disease progression, or up to 2 years.

Also known as: TEDOPI®

Arm B : OSE2101; Arm C : OSE2101 + Pembrolizumab

Pembrolizumab 25 MG/ML [Keytruda] DRUG

400 mg IV infusion on day 1 every 6 weeks until intolerance, disease progression, or up to 2 years.

Also known as: KEYTRUDA®, MK-3475

Arm C : OSE2101 + Pembrolizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed and dated informed consent document for the study, willing and able to comply with protocol requirements, including:
• HLA-A2 phenotype determination by genetic test (blood)
• participation in translational research in HLA-A2 positive
• authorization for long term follow up if HLA-A2 negative
• 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 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
• 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-indications according to 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)
• Randomization must be within 8 weeks of last dose of chemotherapy
• 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):

You may not qualify if:

• 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
• Note: Examples of live vaccines include, but are not limited to, the following:
• measles, mumps, rubella, varicella/zoster, yellow fever, rabies, BCG, and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed as other killed vaccines, if done at least 2 weeks prior the first dose of study drug; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed.
• Prior cancer vaccine therapy
• 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:

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP: lead
• OSE Immunotherapeutics: collaborator
• Merck Sharp & Dohme LLC: collaborator

Study Sites (40)

UZ Leuven

Leuven, 3000, Belgium

Location

Centre Hospitalier de l'Ardenne Vivalia

Libramont, 6800, Belgium

Location

Centre Hospitalier Universitaire de Liège

Liège, 4000, Belgium

Location

ICO Paul Papin

Angers, 49055, France

Location

Institut du Cancer Avignon-Provence

Avignon, 84000, France

Location

Centre Hospitalier de la Côte Basque

Bayonne, 64109, France

Location

CHU Besançon - Hôpital Jean Minjoz

Besançon, 25030, France

Location

Institut Bergonié

Bordeaux, 33076, France

Location

Centre François Baclesse

Caen, 14000, France

Location

Centre d'Oncologie et de Radiothérapie 37

Chambray-lès-Tours, 37170, France

Location

Centre Hospitalier de Cholet

Cholet, 49300, France

Location

Centre Jean PERRIN

Clermont-Ferrand, 63011, France

Location

Centre Georges François Leclerc

Dijon, 21000, France

Location

CHU Grenoble-Alpes - Site Nord (La Tronche)

Grenoble, 38043, France

Location

Centre Oscar Lambret

Lille, 59020, France

Location

CHU Limoges - Dupuytren

Limoges, 87042, France

Location

Hôpital Privé Jean Mermoz

Lyon, 69008, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

ICM - Val d'Aurelle

Montpellier, 34298, France

Location

Hôpital Privé du Confluent

Nantes, 44202, France

Location

Hôpital Pitié-Salpêtrière - AP-HP

Paris, 75013, France

Location

Hôpital Cochin

Paris, 75014, France

Location

Groupe Hospitalier Diaconesses-Croix Saint-Simon

Paris, 75020, France

Location

Center Hospitalier de Pau

Pau, 64000, France

Location

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

Centre CARIO - HPCA

Plérin, 22190, France

Location

Centre Eugène Marquis

Rennes, 35042, France

Location

ICO - Centre René Gauducheau

Saint-Herblain, 44805, France

Location

CHU de Saint-Etienne - Pôle de Cancérologie

Saint-Priest-en-Jarez, 42271, France

Location

Centre Hospitalier Broussais

St-Malo, 35400, France

Location

Institut de Cancérologie de Strasbourg Europe - ICANS

Strasbourg, 67200, France

Location

Institut Claudius Régaud

Toulouse, 31059, France

Location

Gustave Roussy

Villejuif, 94805, France

Location

Universitätsklinikum Carl Gustav Carus

Dresden, 01307, Germany

Location

Evang. Kliniken Essen-Mitte GmbH

Essen, 45136, Germany

Location

Universitätsklinikum Leipzig

Leipzig, 04103, Germany

Location

Universitätsmedizin Mainz

Mainz, 55131, Germany

Location

Universitätsmedizin Mannheim GmbH

Mannheim, 68167, Germany

Location

Universitätsklinikum Ulm

Ulm, 89075, Germany

Location

Related Publications (1)

• Kabirian R, Tredan O, Marme F, Paoletti X, Eberst L, Lebreton C, De La Motte Rouge T, Sabatier R, Angelergues A, Fabbro M, Van Gorp T, Mansi L, Gladieff L, Kaczmarek E, Alexandre J, Grellety T, Favier L, Welz J, Frenel JS, Leary A. TEDOVA: vaccine OSE2101 +/- pembrolizumab as maintenance in platinum-sensitive recurrent ovarian cancer. Future Oncol. 2024;20(35):2699-2708. doi: 10.1080/14796694.2024.2386922. Epub 2024 Aug 19.

  PMID: 39155847 DERIVED

MeSH Terms

Conditions

Ovarian Neoplasms; Recurrence

Interventions

pembrolizumab

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Alexandra LEARY, MD,PHD

  GINECO - Gustave Roussy

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 14, 2021
• First Posted: January 19, 2021
• Study Start: August 5, 2021
• Primary Completion: December 1, 2025
• Study Completion: December 1, 2025
• Last Updated: December 2, 2024

Record last verified: 2024-11

Locations

DE (6); BE (3); FR (31)