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JOURNAL ONKOLOGIE – STUDIE

Study of Chemotherapy With Pembrolizumab (MK-3475) Followed by Maintenance With Olaparib (MK-7339) for the First-Line Treatment of Women With BRCA Non-mutated Advanced Epithelial Ovarian Cancer (EOC) (MK-7339-001/KEYLYNK-001/ENGOT-ov43/GOG-3036)

Rekrutierend

NCT-Nummer:
NCT03740165

Studienbeginn:
Dezember 2018

Letztes Update:
11.06.2021

Wirkstoff:
Pembrolizumab, Placebo for Pembrolizumab, Carboplatin, Paclitaxel, Olaparib, Placebo for olaparib, Bevacizumab, Docetaxel

Indikation (Clinical Trials):
Ovarian Neoplasms, Carcinoma, Ovarian Epithelial, Fallopian Tube Neoplasms, Peritoneal Neoplasms

Geschlecht:
Frauen

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 3

Sponsor:
Merck Sharp & Dohme Corp.

Collaborator:
European Network of Gynaecological Oncological Trial Groups (ENGOT), Gynecologic Oncology Group,

Studienleiter

Medical Director
Study Director
Merck Sharp & Dohme Corp.

Kontakt

Studienlocations
(3 von 227)

Marienhospital Stuttgart Vincenz von Paul Kliniken gGmbH ( Site 0707)
70199 Stuttgart
(Baden-Württemberg)
GermanyRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +4971164893276
» Ansprechpartner anzeigen
Ballarat Health Services ( Site 2202)
3350 Ballarat
AustraliaAktiv, nicht rekrutierend» Google-Maps
Hospital Erasto Gaertner ( Site 2716)
82520-060 Curitiba
BrazilAktiv, nicht rekrutierend» Google-Maps
Hospital de Caridade de Ijui ( Site 2712)
98700-000 Ijui
BrazilAktiv, nicht rekrutierend» Google-Maps
Hospital Nossa Senhora Da Conceicao ( Site 2703)
91350-200 Porto Alegre
BrazilAktiv, nicht rekrutierend» Google-Maps
Fundacion Arturo Lopez Perez FALP ( Site 2800)
7500922 Santiago
ChileAbgeschlossen» Google-Maps
Biomelab S A S ( Site 2900)
080002 Barranquilla
ColombiaAbgeschlossen» Google-Maps
Sociedad de Oncología Y Hematología del Cesar S.A.S. ( Site 2913)
200001 Valledupar
ColombiaAktiv, nicht rekrutierend» Google-Maps
Oncomedica S.A. ( Site 2911)
230002 Monteria
ColombiaAktiv, nicht rekrutierend» Google-Maps
Instituto Nacional de Cancerologia E.S.E ( Site 2910)
110321 Bogota
ColombiaAktiv, nicht rekrutierend» Google-Maps
Clinica Colsanitas S.A. Sede Clinica Universitaria Colombia ( Site 2912)
111321 Bogota
ColombiaAktiv, nicht rekrutierend» Google-Maps
Centro Medico Imbanaco de Cali S.A ( Site 2909)
760042 Cali
ColombiaAktiv, nicht rekrutierend» Google-Maps
Hemato Oncologos S.A. ( Site 2906)
760042 Cali
ColombiaAktiv, nicht rekrutierend» Google-Maps
CHU de Brest -Site Hopital Morvan ( Site 0616)
29200 Brest
FranceAktiv, nicht rekrutierend» Google-Maps
National Cancer Center Hospital East ( Site 2602)
277-8577 Kashiwa
JapanAktiv, nicht rekrutierend» Google-Maps
National Defense Medical College Hospital ( Site 2608)
359-8513 Tokorozawa
JapanAktiv, nicht rekrutierend» Google-Maps
Kagoshima City Hospital ( Site 2612)
890-8760 Kagoshima
JapanAktiv, nicht rekrutierend» Google-Maps
Seoul National University Bundang Hospital ( Site 2404)
13620 Seongnam-si
Korea, Republic ofAktiv, nicht rekrutierend» Google-Maps
Seoul National University Hospital ( Site 2403)
03080 Seoul
Korea, Republic ofAktiv, nicht rekrutierend» Google-Maps
Severance Hospital Yonsei University Health System ( Site 2400)
03722 Seoul
Korea, Republic ofAktiv, nicht rekrutierend» Google-Maps
Asan Medical Center ( Site 2402)
05505 Seoul
Korea, Republic ofAktiv, nicht rekrutierend» Google-Maps
Samsung Medical Center ( Site 2401)
06351 Seoul
Korea, Republic ofAktiv, nicht rekrutierend» Google-Maps
Narodowy Instytut Onkologii im. Marii Sklodowskiej-Curie - Panstwowy Instytut Badawczy w Warszawie (
02-781 Warszawa
PolandRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +48225462295
» Ansprechpartner anzeigen
Szpital Kliniczny im. Przemienienia Panskiego Uniwersytetu Medycznego im. K. Marcinkowskiego w Pozna
61-848 Poznan
PolandRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +48618549014
» Ansprechpartner anzeigen
Arkhangelsk Clinical Oncological Dispensary ( Site 1508)
163045 Arkhangelsk
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Republican Clinical Oncology Dispensary of Republic of Bashkortostan ( Site 1507)
450054 Ufa
Russian FederationAktiv, nicht rekrutierend» Google-Maps
A. Tsyb Medical Radiological Research Center ( Site 1513)
249036 Obninsk
Russian FederationAktiv, nicht rekrutierend» Google-Maps
FSBI National Medical Oncology Research Center n.a. N.N. Blokhina ( Site 1500)
115478 Moscow
Russian FederationAktiv, nicht rekrutierend» Google-Maps
FSCC of Special Types of Med. Care and Technologies ( Site 1503)
115682 Moscow
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Medical Rehabilitation Center ( Site 1502)
125367 Moscow
Russian FederationAktiv, nicht rekrutierend» Google-Maps
City Clinical Oncology Center ( Site 1505)
198255 Saint Petersburg
Russian FederationAktiv, nicht rekrutierend» Google-Maps
National Medical Research Center of Oncology N.A. N.N. Petrov ( Site 1504)
197758 Saint-Petersburg
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Republican Clinical Oncology Dispensary of Tatarstan MoH ( Site 1509)
420029 Kazan
Russian FederationAktiv, nicht rekrutierend» Google-Maps
Groote Schuur Hospital ( Site 1704)
7925 Cape Town
South AfricaSchwebend» Google-Maps
Instituto Catalan de Oncologia ICO - Hospital Duran i Reynals ( Site 1603)
08909 Hospitalet de Llobregat
SpainRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +34932607333
» Ansprechpartner anzeigen
Changhua Christian Hospital ( Site 2507)
50006 Changhua
TaiwanAktiv, nicht rekrutierend» Google-Maps
China Medical University Hospital ( Site 2506)
40447 Taichung
TaiwanAbgeschlossen» Google-Maps
Municipal non-profit Enterprise Khmelnytskyi Regional Antitu-Gynecological Oncology department, Poli
29009 Khmelnytskyi
UkraineRekrutierend» Google-Maps
Ansprechpartner:
Study Coordinator
Phone: +380979242755
» Ansprechpartner anzeigen
MI Odessa Regional Oncological Centre ( Site 2121)
65055 Odesa
UkraineAktiv, nicht rekrutierend» Google-Maps
Central City Clinical Hospital ( Site 2150)
88000 Uzhgorod
UkraineAktiv, nicht rekrutierend» Google-Maps
Kyiv City Clinical Oncological Center ( Site 2140)
03115 Kyiv
UkraineAktiv, nicht rekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

Detailed Description:

Following a lead-in period during which all participants receive a single 3-week cycle of

carboplatin/paclitaxel*, participants will be randomly assigned in to one of three treatment

arms:

- Pembrolizumab + Olaparib,

- Pembrolizumab + Placebo for Olaparib

- Placebo for Pembrolizumab + Placebo for Olaparib

- At Investigator's discretion and prior to participant randomization, one of the

following carboplatin/paclitaxel regimens is to be selected:

1. up to 5 cycles of carboplatin Area Under the Curve (AUC)5 or AUC6 AND

paclitaxel 175 mg/m^2 on Day 1 of each 3-week cycle

2. up to 5 cycles of carboplatin AUC5 or AUC6 on Day 1 of each 3-week cycle AND

paclitaxel 80 mg/m^2 on Days 1, 8 and 15 of each 3-week cycle; or

3. up to 5 cycles of carboplatin AUC2 or AUC2.7 AND paclitaxel 60 mg/m^2 on Days

1, 8 and 15 of each 3-week cycle.

Docetaxel may be considered for participants who experience either a severe hypersensitivity

reaction to paclitaxel or an AE requiring discontinuation of paclitaxel only after

consultation with the Sponsor. The recommended dose as determined by the Scottish

Gynaecological Cancer Trials Group is Docetaxel 75 mg/m^2 Q3W plus carboplatin AUC 5 Q3W.

Ein-/Ausschlusskriterien

Inclusion Criteria:

- Has histologically confirmed International Federation of Gynecology and Obstetrics

(FIGO) Stage III or Stage IV EOC (high-grade predominantly serous, endometrioid (any

grade), carcinosarcoma, mixed mullerian with high-grade serous component, clear cell,

or low-grade serous OC), primary peritoneal cancer, or fallopian tube cancer

- Has just completed primary debulking surgery or is eligible for primary debulking

surgery or is a potential candidate for interval debulking surgery

- Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the

adjuvant or neoadjuvant setting

- Candidates for neoadjuvant chemotherapy, has a cancer antigen 125 (CA-125)

(kilounits/L):carcinoembryonic antigen (CEA; ng/mL) ratio greater than or equal to 25

- Is able to provide a newly obtained core or excisional biopsy of a tumor lesion for

prospective testing of BRCA1/2 and Programmed Cell Death-Ligand 1 (PD-L1) tumor

markers status prior to randomization

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1, as

assessed within 7 days prior to initiating chemotherapy in the lead-in period and

within 3 days prior to Day 1 of Cycle 1

- Female participants are not pregnant, not breastfeeding, and at least 1 of the

following conditions applies: a.) Not a woman of childbearing potential (WOCBP) OR b.)

Is a WOCBP and using a contraceptive method that is highly effective, with low user

dependency, or be abstinent from heterosexual intercourse as their preferred and usual

lifestyle, during the Treatment Period and for at least 120 days following the last

dose of pembrolizumab (or pembrolizumab placebo) and bevacizumab (if administered), at

least 180 days following the last dose of olaparib (or olaparib placebo), and at least

210 days following the last dose of chemotherapy and agrees not to donate eggs (ova,

oocytes) to others or freeze/store for her own use for the purpose of reproduction

during this period. The investigator should evaluate the potential for contraceptive

method failure in relationship to the first dose of study treatment. A WOCBP must have

a negative highly sensitive pregnancy test within either 24 hours (urine) or 72 hours

(serum) before the first dose of study treatment. If a urine test cannot be confirmed

as negative, a serum pregnancy test is required. The investigator is responsible for

review of medical history, menstrual history, and recent sexual activity to decrease

the risk for inclusion of a woman with an early undetected pregnancy. Contraceptive

use by women should be consistent with local regulations regarding the methods of

contraception for those participating in clinical studies

- Has adequate organ function

Exclusion Criteria:

- Has mucinous, germ cell, or borderline tumor of the ovary

- Has a known or suspected deleterious mutation (germline or somatic) in either BRCA1 or

BRCA2

- Has a history of non-infectious pneumonitis that required treatment with steroids or

currently has pneumonitis

- Has either myelodysplastic syndrome (MDS)/acute myeloid leukemia (AML) or has features

suggestive of MDS/AML

- Has a known additional malignancy that is progressing or has required active treatment

in the last 3 years Note: Participants with basal cell carcinoma of the skin, squamous

cell carcinoma of the skin, or carcinoma in situ (e.g. ductal carcinoma in situ,

cervical carcinoma in situ) that has undergone potentially curative therapy are not

excluded.

- Has ongoing Grade 3 or Grade 4 toxicity, excluding alopecia, following chemotherapy

administered during the lead-in period

- Has known active central nervous system metastases and/or carcinomatous meningitis.

Participants with brain metastases may participate provided they were previously

treated (except with chemotherapy) and are radiologically stable, clinically stable,

and no steroids were used for the management of symptoms related to brain metastases

within 14 days prior to randomization. Stable brain metastases should be established

prior to the first dose of study medication lead-in chemotherapy

- Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy

(dosing >10 mg daily of prednisone equivalent) or any other form of immunosuppressive

therapy within 7 days prior to randomization

- Has an 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) Note: Replacement therapy (e.g. thyroxine, insulin, or

physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency)

is not considered a form of systemic treatment and is allowed.

- Has a known history of active tuberculosis (TB; Bacillus Tuberculosis)

- Has an active infection requiring systemic therapy

- Has received colony-stimulating factors (eg, granulocyte colony stimulating factor

[G-CSF], granulocyte macrophage colony-stimulating factor [GM-CSF] or recombinant

erythropoietin) within 4 weeks prior to receiving chemotherapy during the lead-in

period

- Is considered to be of poor medical risk due to a serious, uncontrolled medical

disorder, non-malignant systemic disease or active, uncontrolled infection

- Has had surgery to treat borderline tumors, early stage EOC, or early stage fallopian

tube cancer <6 months prior to screening

- Has a known history of human immunodeficiency virus (HIV) infection

- Has a known history of hepatitis B (defined as hepatitis B surface antigen [HBsAg]

reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is

detected) infection. Testing for hepatitis B or hepatitis C is required at screening

only if mandated by local health authority. Note: Participants with a history of

hepatitis B but who are HBsAg negative are eligible for the study

- Is either unable to swallow orally administered medication or has a gastrointestinal

(GI) disorder affecting absorption (e.g. gastrectomy, partial bowel obstruction,

malabsorption)

- Has uncontrolled hypertension

- Has current, clinically relevant bowel obstruction (including sub-occlusive disease),

abdominal fistula or GI perforation, related to underlying EOC (for participants

receiving bevacizumab)

- Has a history of hemorrhage, hemoptysis or active GI bleeding within 6 months prior to

randomization (for participants receiving bevacizumab)

- Is a WOCBP who has a positive urine pregnancy test within 72 hours before the first

dose of chemotherapy in the lead-in period and within 72 hours prior to Day 1 of Cycle

1, is pregnant or breastfeeding, or is expecting to conceive children within the

projected duration of the study, starting with screening through 120 days following

the last dose of pembrolizumab (or pembrolizumab placebo) and bevacizumab (if

administered), at least 180 days following the last dose of olaparib (or olaparib

placebo), and at least 210 days following the last dose of chemotherapy

- Has received prior treatment for any stage of OC, including radiation or systemic

anti-cancer therapy (e.g. chemotherapy, hormonal therapy, immunotherapy,

investigational therapy)

- Has received prior therapy with an anti-Programmed Cell Death-1 (anti-PD-1),

anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or

co-inhibitory T-cell receptor (e.g. cytotoxic T lymphocyte antigen-4 [CTLA-4], OX 40,

CD137)

- Has received prior therapy with either olaparib or any other poly(adenosine-ribose)

polymerase (PARP) inhibitor

- Has intraperitoneal chemotherapy planned or has been administered as first-line

therapy

- Has received a live vaccine within 30 days prior to the first dose of study treatment

on Day 1 of Cycle 1

- Has severe hypersensitivity (≥Grade 3) to pembrolizumab, olaparib, carboplatin,

paclitaxel or bevacizumab (if using) and/or any of their excipients

- Is currently receiving either strong (e.g. itraconazole, telithromycin,

clarithromycin, protease inhibitors boosted with ritonavir or cobicistat, indinavir,

saquinavir, nelfinavir, boceprevir, telaprevir) or moderate (eg, ciprofloxacin,

erythromycin, diltiazem, fluconazole, verapamil) inhibitors of cytochrome P450

(CYP)3A4 that cannot be discontinued for the duration of the study

- Is currently receiving either strong (e.g. phenobarbital, phenytoin, rifampicin,

rifabutin, rifapentine, carbamazepine, nevirapine, and St John's Wort) or moderate

(e.g. bosentan, efavirenz, modafinil) inducers of CYP3A4 that cannot be discontinued

for the duration of the study

- Has received whole blood transfusions in the last 120 days prior to randomization

- Is currently participating or has participated in a study of an investigational agent

or has used an investigational device within 4 weeks (28 days) of starting

chemotherapy in the Lead-in Period

- Has resting electrocardiogram (ECG) indicating uncontrolled, potentially reversible

cardiac conditions or participant has congenital long QT syndrome

- Has had an allogenic tissue/solid organ transplant, has received previous allogenic

bone-marrow transplant, or has received double umbilical cord transplantation

- Either has had major surgery within 3 weeks of randomization or has not recovered from

any effects of any major surgery

Studien-Rationale

Primary outcome:

1. Progression-Free Survival (PFS) Per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) as Assessed by the Investigator in Participants with Programmed Death-Ligand 1 (PD-L1)-Positive Tumors (Combined Positive Score [CPS]≥10) Tumors (Time Frame - Up to approximately 57 months):
PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on Investigator assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by the Investigator will be reported for participants with PD-L1-positive (CPS≥10) tumors.

2. PFS Per RECIST 1.1 as Assessed by the Investigator in All Participants (Time Frame - Up to approximately 57 months):
PFS is defined as the time from randomization to the first documented progressive disease (PD) per RECIST 1.1 based on Investigator assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by the Investigator will be reported for all participants.

Secondary outcome:

1. Overall Survival (OS) in All Participants (Time Frame - Up to approximately 6 years):
OS is defined as the time from the date of randomization to death due to any cause. The OS will be reported for all participants.

2. PFS Per RECIST 1.1 as Assessed by Blinded Independent Central Review (BICR) in Participants with PD-L1-Positive Tumors (CPS≥10) Tumors (Time Frame - Up to approximately 57 months):
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by blinded independent central review will be reported for participants with PD-L1-positive (CPS≥10) tumors.

3. PFS Per RECIST 1.1 as Assessed by BICR in All Participants (Time Frame - Up to approximately 57 months):
PFS is defined as the time from randomization to the first documented disease progression per RECIST 1.1 based on blinded independent central review assessment or death due to any cause, whichever occurs first. Per RECIST 1.1, PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. Note: The appearance of one or more lesions and the unequivocal progression of non-target lesions is also considered PD. The PFS per RECIST 1.1 as assessed by blinded independent central review will be reported for all participants.

4. PFS After Next-line Treatment (PFS2) Following Discontinuation of Study Treatment as Assessed by the Investigator in Participants with PD-L1-Positive Tumors (CPS≥10) Tumors (Time Frame - Up to approximately 78 months):
PFS2 is defined as the time from randomization until PD on next-line treatment or death due to any cause, whichever occurs first. The PFS2 per Investigator assessment will be reported for participants with PD-L1-positive (CPS≥10) tumors.

5. PFS2 Following Discontinuation of Study Treatment as Assessed by the Investigator in All Participants (Time Frame - Up to approximately 78 months):
PFS2 is defined as the time from randomization until PD on next-line treatment or death due to any cause, whichever occurs first. The PFS2 per Investigator assessment will be reported for all participants.

6. Number of Participants Who Experience an Adverse Event (AE) (Time Frame - Up to approximately 73 months):
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who experience an AE will be reported.

7. Number of Participants Who Discontinue Study Treatment Due to an AE (Time Frame - Up to approximately 6 years):
An AE is any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. The number of participants who discontinue study treatment due to an AE will be reported.

8. Change from Baseline in Global Health Status/Quality of Life (GHS/QoL) Score Using Questions from the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) (Time Frame - Baseline and End of Study Participation (Up to approximately 6 years)):
Participants are asked to answer 2 questions from the EORTC QLQ-C30 about their GHS: "How would you rate your overall health during the past week?" and "How would you rate your overall quality of life during the past week?" Responses are based on a 7-point scale (1=Very poor; 7=Excellent), with a higher score indicating a better global health status. The change from baseline in GHS/QoL score of participants will be reported.

9. Change from Baseline in Abdominal and Gastrointestinal (Abdominal/GI) Symptoms Score Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale (Time Frame - Baseline and End of Study Participation (Up to approximately 6 years)):
Participants are asked to answer 6 questions from the EORTC QoL Questionnaire-Ovarian Cancer (QLQ-OV28) abdominal/GI symptom scale about abdominal pain, bloated feeling in abdomen/stomach, changes in clothing fit, changes in bowel habit, flatulence and stomach fullness when eating. Responses are based on a 4-point scale (1=Not at all; 4=Very much), with a lower score indicating better abdominal/GI symptoms. The change from baseline in abdominal/GI symptom score of participants will be reported.

10. Time to First Subsequent Anti-cancer Treatment (TFST) (Time Frame - Up to approximately 6 years):
TFST is defined as the time from randomization to initiation of first subsequent anti-cancer treatment or death due to any cause, whichever occurs first. The TFST will be reported.

11. Time to Second Subsequent Anti-cancer Treatment (TSST) (Time Frame - Up to approximately 6 years):
TSST is defined as the time from randomization to initiation of second subsequent anti-cancer treatment or death due to any cause, whichever occurs first. The TSST will be reported.

12. Time to Discontinuation of Study Treatment or Death (TDT) (Time Frame - Up to approximately 6 years):
TDT is defined as the time from the date of randomization to discontinuation of study treatment or death due to any cause, whichever occurs first. The TDT will be reported.

13. Pathological Complete Response (pCR) Rate (Time Frame - Up to approximately 30 months):
pCR is defined as all surgical specimens collected during the interval debulking surgery are microscopically negative for malignancy. The pCR rate for all surgical specimens will be reported.

14. Time Without Symptom of Disease Progression or Toxicity of Treatment (TWiST) (Time Frame - Up to approximately 6 years):
TWiST is defined as the time from randomization to disease progression or treatment-related toxicity, whichever occurs first. The TWiST will be reported.

Studien-Arme

  • Experimental: Pembrolizumab + Olaparib
    Participants receive carboplatin/paclitaxel via intravenous (IV) infusion for five 3-week cycles PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 cycles PLUS olaparib 300 mg via oral tablet twice each day (BID), starting with Cycle 7. Participants who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion.
  • Experimental: Pembrolizumab + Placebo for Olaparib
    Participants receive carboplatin/paclitaxel via IV infusion for five 3-week cycles starting in Cycle 1 PLUS pembrolizumab 200 mg via IV infusion on Day 1 of each 3-week cycle for up to 35 cycles PLUS placebo for olaparib via oral tablet BID, starting with Cycle 7. Participants who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion.
  • Active Comparator: Placebo for Pembrolizumab + Placebo for Olaparib
    Participants receive carboplatin/paclitaxel via IV infusion for five 3-week cycles PLUS placebo for pembrolizumab (normal saline or dextrose) via IV infusion on Day 1 of each 3-week cycle for up to 35 cycles PLUS placebo for olaparib via oral tablet BID, starting with Cycle 7. Participants who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 Q3W) plus carboplatin AUC 5 Q3W after Sponsor consultation. Participants may also receive bevacizumab via IV infusion on Day 1 of each 3-week cycle at the Investigator's discretion.

Geprüfte Regime

  • Pembrolizumab (MK-3475 / KEYTRUDA® / ):
    IV infusion
  • Placebo for pembrolizumab (normal saline or dextrose):
    IV infusion
  • Carboplatin (PARAPLATIN®):
    IV infusion
  • Paclitaxel (TAXOL®):
    IV infusion
  • Olaparib (MK-7339 / LYNPARZA® / ):
    Oral tablet
  • Placebo for olaparib:
    Oral tablet
  • Bevacizumab (AVASTIN®):
    IV infusion
  • Docetaxel:
    IV infusion

Quelle: ClinicalTrials.gov


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