PEMBRO With Chemo in Neo Adj Treatment of Ovarian Cancer .

NCT03275506 | Completed Phase 2 DMC

• 1 other identifier: OV126b
• Study Type: interventional
• Target: 91
• Locations: 1 country
• Sites: 22

Brief Summary

There are several data suggesting that pembrolizumab and bevacizumab may be synergistic. Enhanced tumor angiogenesis is commonly associated with absence of tumor-infiltrating T cells in patients. There is evidence in OC that tumor expression of VEGF is negatively correlated to the density of CD3+TILs and this phenotype is associated with early recurrence, consistent with prior studies showing a correlation of VEGF to early recurrence and short survival. Furthermore, in ascites, high levels of VEGF correlate to low numbers of NK T-like CD3+CD56+ cells This randomized phase II study aims to evaluate the efficacy of pembrolizumab in combina-tion with the standard neo adjuvant chemotherapy followed by IDS and the safety of this strategy in patients with advanced ovarian cancer. We assume that its administration in the neo adjuvant setting combination with standard of care (4 cycles of standard chemotherapy) would improve the response rate and consequently will help to achieve optimal debulking rate at IDS. After surgery, patients will continue to be treated with standard of care (chemotherapy for 2 to 5 cycles plus or less bevacizumab) or the same combination plus pembrolizumab (keytruda).

Conditions

Ovarian Cancer Stage IV

Keywords

neoadjuvant; debulking surgery

Outcome Measures

Primary Outcomes (1)

• Primary objective

  Efficacy: Complete Resection Rate (CC0) after interval debulking surgery

  Average of 4 months after the randomization of the last patient.

Secondary Outcomes (11)

• Secondary objective

  Average of 4 months after the randomization of the last patient.

• Secondary objective

  Average of 4 months after the randomization of the last patient.

• Secondary objective

  Average of 4 months after the randomization of the last patient.

• Secondary objective

  Average of 3 months after the first neo-adjuvant cycle.

• Secondary objective

  From the date of randomization until the end of treatment.

Study Arms (2)

Pembrolizumab + Chemotherapy

EXPERIMENTAL

Arm B (n=60): 4 neo-adjuvant cycles of standard 3 weekly Pembrolizumab 200 mg then carboplatin (AUC5 or 6) and paclitaxel (175mg/m²) Arm B: Pembrolizumab 200 mg then carboplatin (AUC5 or 6) and paclitaxel (175mg/m²), +/- bevacizumab (15 mg/kg Q3W) The total number of cycles of chemotherapy will be 6 cycles from the start of the neo-adjuvant chemotherapy. Three additional cycles are allowed if required (maximum 9 cycles in total). The planning of administration or not of bevacizumab will be defined before the randomization and could not be modified (stratification factor). After chemotherapy: * In the Arm A \& B, for patients receiving bevacizumab (as standard therapy) (15 mg/kg Q3W), this will be continue until a maximum of 15 months in total from the beginning of the adjuvant therapy. * In the arm B, patient will receive Pembrolizumab 200 mg until a maximum of 15 months in total from the beginning of the adjuvant therapy.

Drug: Pembrolizumab Injectable Product - Chemotherapy - Bevacizumab

Chemotherapy alone

ACTIVE COMPARATOR

Arm A (n=30): 4 neo-adjuvant cycles of standard 3 weekly carboplatin (AUC5 or 6) and paclitaxel (175mg/m²) Arm A: carboplatin (AUC5 or 6) and paclitaxel (175mg/m²), q3 weeks +/- bevacizumab (15 mg/kg Q3W) The total number of cycles of chemotherapy will be 6 cycles from the start of the neo-adjuvant chemotherapy. Three additional cycles are allowed if required (maximum 9 cycles in total). The planning of administration or not of bevacizumab will be defined before the randomization and could not be modified (stratification factor). After chemotherapy: \- In the Arm A \& B, for patients receiving bevacizumab (as standard therapy) (15 mg/kg Q3W), this will be continue until a maximum of 15 months in total from the beginning of the adjuvant therapy.

Drug: Chemotherapy - Bevacizumab

Interventions

Pembrolizumab Injectable Product - Chemotherapy - Bevacizumab DRUG

Pembrolizumab 200 mg then carboplatin (AUC5 or 6) and paclitaxel (175mg/m²), +/- bevacizumab (15 mg/kg Q3W)

Pembrolizumab + Chemotherapy

Chemotherapy - Bevacizumab DRUG

Carboplatin (AUC5 or 6) and paclitaxel (175mg/m²), +/- bevacizumab (15 mg/kg Q3W)

Chemotherapy alone

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Be willing and able to provide written informed consent/assent for the trial.
• Woman ≥ 18 and ≤ 75 years old on day of signing informed consent
• Histologically confirmed diagnosis of epithelial ovarian carcinoma or fallopian tube carcinoma or primary peri-toneal carcinoma with the exception of mucinous histology. Histology should be obtained by laparoscopy (or by laparotomy).
• High grade serous or endometrioid (see appendix 1 bis)
• Advanced FIGO stage IIIC to IV patient not able to receive primary debulking surgery for which neo adjuvant chemotherapy with carboplatin and paclitaxel is recommended (primary debulking surgery has been denied after an evaluation through laparoscopy or laparotomy). Patients with extra abdominal metastasis (FIGO 2014 Stage IV) can be included in case of completely resectable metastasis.
• Eligible for carboplatin and paclitaxel chemotherapy in accordance with local standards of care following cy-toreductive surgery.
• Interval complete surgery anticipated in a center with excellence.
• ECOG performance status (PS) ≤ 2.
• Life expectancy of at least 6 months,
• Interval between diagnosis and enrolment (informed consent) ≤ 8 weeks,
• Be willing to provide blood, and tissue from a newly obtained core or excisional biopsy of a tumor lesion. Newly-obtained is defined as a specimen obtained up to 8 weeks (56 days) prior to initiation of treatment on Day 1.
• Demonstrate adequate organ function as defined in the table below, all screening labs should be performed within 7 days before randomization.
• Adequate hematological laboratory value: Absolute neutrophil count (ANC): ≥1,500/mm3
• Platelets : ≥100,000/mm3
• Hemoglobin : ≥9 g/dL or ≥5.6 mmol/L without transfusion or EPO dependency (within 7 days of assessment)

You may not qualify if:

• Histological diagnosis of malignant tumor of non-epithelial origin (e.g. germ cell tumor, sex cord-stromal tumor) of the ovary, the fallopian tube or peritoneum or borderline tumor of the ovary (tumor of low malignant potential).
• Patients with extra abdominal metastasis (FIGO 2014 Stage IV) not completely resectable, as e.g. multiple parenchymal lung metastases (preferably histologically proven), non resectable lymph node metastases, brain me-tastases.
• Prior systemic therapy for ovarian cancer (e.g. chemotherapy, monoclonal antibody therapy, oral targeted therapy, hormonal therapy),
• Prior radiotherapy to the abdomen or prior radiotherapy to an extra-abdominal target volume that would bear the risk of increased toxicity of chemotherapy,
• Serious illness or concomitant non-oncological disease such as neurologic, psychiatric or infectious disease, active ulcers (gastrointestinal tract, skin) or a laboratory abnormality that may Increase the risk associated with study participation or study drug administration and in the judgment of the investigator would make the patient inappropriate for entry into the study,
• Any contraindications for therapy with paclitaxel or carboplatin, e.g. a history of severe hypersensitivity reactions to paclitaxel or platinum-containing compounds and their excipients, or other drugs formulated with Pol-yoxyl 35Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment.
• Diagnosis of immunodeficiency or receiving prolonged period of systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment.
• Known history of active Bacillus Tuberculosis (TB)
• Hypersensitivity to pembrolizumab or any of its excipients.
• Prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study Day 1 or no recovery (i.e., ≤ Grade 1 or at baseline) from adverse events due to agents administered more than 4 weeks earlier.
• Known additional malignancy that is progressing or requires active treatment. Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
• Known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable (without evidence of progression by imaging for at least four weeks prior to the first dose of trial treatment and any neurologic symptoms have returned to baseline), have no evidence of new or enlarging brain metastases, and are not using steroids for at least 7 days prior to trial treatment. This exception does not include carcinomatous meningitis which is excluded regardless of clinical stability.
• 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 (e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent.
• History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).

Sponsors & Collaborators

• ARCAGY/ GINECO GROUP: lead

Study Sites (22)

Hôpital Henri Duffaut

Avignon, 84000, France

Location

CHRU Jean Minjoz

Besançon, 25030, France

Location

Centre François Baclesse

Caen, 14000, France

Location

Centre Jean Perrin

Clermont-Ferrand, 63000, France

Location

Centre Hospitalier Intercommunal de Créteil

Créteil, 94010, France

Location

Centre Georges François Leclerc

Dijon, 21079, France

Location

Centre Hospitalier Départemental Les Oudairies

La Roche-sur-Yon, 85925, France

Location

Centre Hospitalier Universitaire Dupuytren

Limoges, 87042, France

Location

Centre Léon Bérard

Lyon, 69373, France

Location

Hôpital Privé Jean Mermoz

Lyon, 69373, France

Location

Institut Paoli Calmettes

Marseille, 13009, France

Location

Centre Hospitalier Régional d'Orléans

Orléans, 45067, France

Location

Groupe Hospitalier Diaconesses-Croix Saint Simon

Paris, 75020, France

Location

Institut Mutualiste Montsouris-Jourdan

Paris, 75674, France

Location

Centre CARIO-HPCA

Plérin, 22190, France

Location

Institut Jean Godinot

Reims, 51056, France

Location

Centre Henri Becquerel

Rouen, 76038, France

Location

ICO Centre René Gauducheau

Saint-Herblain, 44805, France

Location

CHU Saint-Etienne - Pôle de Cancérologie

Saint-Priest-en-Jarez, 42271, France

Location

Hôpitaux Universitaires de Strasbourg

Strasbourg, 67091, France

Location

Institut Claudius Regaud

Toulouse, 31059, France

Location

Clinique Pasteur

Toulouse, 31076, France

Location

Related Publications (1)

• Collet L, Ardin M, Venet D, Berthet J, Ghamry-Barrin S, Treilleux I, Noel JC, Leheurteur M, Meunier J, Bengrine Lefevre L, Martinez M, Priou F, Selle F, Just PA, Bataillon G, Rothe F, Sotiriou C, Caux C, Dubois B, Ray-Coquard I, Le Saux O. Unraveling the Tumor Microenvironment and PD-L1 Expression across Tissue Types in High-Grade Serous Ovarian Cancer in the NeoPembrOV/GINECO Phase II Randomized Trial. Clin Cancer Res. 2025 Aug 1;31(15):3317-3331. doi: 10.1158/1078-0432.CCR-24-2712.

  PMID: 40378056 DERIVED

Related Links

• Acces to detailled results

MeSH Terms

Conditions

Ovarian Neoplasms

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

Study Officials

• Isabelle RAY-COQUARD, MD, PhD

  isabelle.ray-coquard@lyon.unicancer.fr

  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

Model Details: open-label, multicentric

Study Record Dates

• First Submitted: July 18, 2017
• First Posted: September 7, 2017
• Study Start: February 26, 2018
• Primary Completion: September 30, 2020
• Study Completion: March 19, 2024
• Last Updated: September 11, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

FR (22)