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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/ct2/show/NCT05116189




Registration number
NCT05116189
Ethics application status
Date submitted
28/10/2021
Date registered
10/11/2021
Date last updated
9/02/2024

Titles & IDs
Public title
Pembrolizumab/Placebo Plus Paclitaxel With or Without Bevacizumab for Platinum-resistant Recurrent Ovarian Cancer (MK-3475-B96/KEYNOTE-B96/ENGOT-ov65)
Scientific title
A Phase 3, Randomized, Double-Blind Study of Pembrolizumab Versus Placebo in Combination With Paclitaxel With or Without Bevacizumab for the Treatment of Platinum-resistant Recurrent Ovarian Cancer (KEYNOTE-B96/ENGOT-ov65)
Secondary ID [1] 0 0
MK-3475-B96
Secondary ID [2] 0 0
3475-B96
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Ovarian Cancer 0 0
Carcinoma, Ovarian Epithelial 0 0
Fallopian Tube Neoplasms 0 0
Condition category
Condition code
Cancer 0 0 0 0
Ovarian and primary peritoneal
Cancer 0 0 0 0
Womb (Uterine or endometrial cancer)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - Pembrolizumab
Treatment: Drugs - Paclitaxel
Treatment: Drugs - Bevacizumab
Other interventions - Placebo for pembrolizumab
Treatment: Drugs - Docetaxel

Experimental: Pembrolizumab + paclitaxel ± bevacizumab - Participants receive pembrolizumab 400 mg via intravenous (IV) infusion for eighteen 6-week cycles (approximately 2 years) PLUS paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 every 3 weeks [Q3W]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.

Placebo Comparator: Placebo + paclitaxel ± bevacizumab - Participants receive placebo via IV infusion for eighteen 6-week cycles (approximately 2 years) PLUS paclitaxel 80 mg/m^2 via IV infusion on Days 1, 8, and 15 of each 3-week cycle until intolerance or disease progression. Participants who experience severe hypersensitivity reaction to paclitaxel or an AE requiring discontinuation of paclitaxel may receive docetaxel (75 mg/m^2 every 3 weeks [Q3W]) after Sponsor consultation. Participants may also receive bevacizumab 10 mg/kg via IV infusion of each 2-week cycle until intolerance, disease progression, or at the Investigator's discretion.


Other interventions: Pembrolizumab
IV infusion

Treatment: Drugs: Paclitaxel
IV infusion

Treatment: Drugs: Bevacizumab
IV infusion

Other interventions: Placebo for pembrolizumab
IV infusion

Treatment: Drugs: Docetaxel
IV infusion
Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator
Timepoint [1] 0 0
Up to ~38 months
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to ~64 months
Secondary outcome [2] 0 0
PFS per RECIST 1.1 by Blinded Independent Central Review (BICR)
Timepoint [2] 0 0
Up to ~38 months
Secondary outcome [3] 0 0
Number of Participants who Experience an Adverse Event (AE)
Timepoint [3] 0 0
Up to ~64 months
Secondary outcome [4] 0 0
Number of Participants who Discontinue Study Treatment due to an AE
Timepoint [4] 0 0
Up to ~64 months
Secondary outcome [5] 0 0
Change From Baseline in Global Health Status/Quality of Life (GHS/Qol) Score (Items 29 and 30) Using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30 (EORTC QLQ-C30)
Timepoint [5] 0 0
Baseline and up to ~64 months
Secondary outcome [6] 0 0
Time to Deterioration (TTD) in the GHS/Qol Score (Items 29 and 30) Using the EORTC QLQ-C30
Timepoint [6] 0 0
Up to ~64 months
Secondary outcome [7] 0 0
Change From Baseline in the Abdominal and Gastrointestinal (GI) Symptoms Score (Items 31 to 36) Using the EORTC Quality of Life Questionnaire-Ovarian Cancer (QLQ-OV28) Abdominal/GI Symptom Scale
Timepoint [7] 0 0
Baseline and up to ~64 months
Secondary outcome [8] 0 0
TTD in the Abdominal and GI Symptoms Score (Items 31 to 36) Using the EORTC QLQ-OV28 Abdominal/GI Symptom Scale
Timepoint [8] 0 0
Up to ~64 months

Eligibility
Key inclusion criteria
- Has histologically confirmed epithelial ovarian, fallopian tube, or primary peritoneal
carcinoma.

- Has received 1 or 2 prior lines of systemic therapy for ovarian cancer (OC), including
at least 1 prior platinum-based therapy. Participants may have received a prior poly
(ADP-ribose) polymerase inhibitor (PARPi), anti-PD-1/anti-PD-L1 therapy, bevacizumab,
or hormonal therapy; these will not be considered a separate line of therapy. Any
chemotherapy regimen change due to toxicity in the absence of disease progression will
be considered part of the same line of therapy.

- Has provided documented informed consent for the study.

- Has radiographic evidence of disease progression within 6 months (180 days) after the
last dose of platinum-based chemotherapy for OC (i.e., platinum-resistant disease).

- Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).

- Has an Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 1 assessed
within 3 days before randomization.

- For a female participant, she is not pregnant or breastfeeding, and at least one of
the following conditions applies: Is not a woman of childbearing potential (WOCBP) OR
Is a WOCBP and uses a contraceptive method that is highly effective (with a failure
rate of <1% per year).

- Has radiographically evaluable disease, either measurable or nonmeasurable per RECIST
1.1, as assessed by the local site investigator.

- Archival tumor tissue sample or newly obtained core or incisional/excisional biopsy of
a tumor lesion not previously irradiated has been provided.

- Have adequate organ function.
Minimum age
18 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
No
Key exclusion criteria
- Has nonepithelial cancers, borderline tumors, mucinous, seromucinous that is
predominantly mucinous, malignant Brenner's tumor and undifferentiated carcinoma.

- Has primary platinum-refractory disease, defined as disease that has progressed per
radiographic imaging while receiving or within 28 days of the last dose of first-line
platinum-based therapy.

- Has prior disease progression on weekly paclitaxel alone.

- Has received >2 prior lines of systemic therapy for OC.

- Has received prior systemic anticancer therapy including investigational agents or
maintenance therapy (including bevacizumab maintenance therapy), within 4 weeks before
randomization.

- Has received prior radiation therapy within 2 weeks of start of study intervention.

- Has not recovered adequately from surgery and/or any complications from the surgery.

- Has received colony-stimulating factors (e.g., granulocyte colony-stimulating factor
[G-CSF], granulocyte-macrophage colony-stimulating factor,[GM-CSF] or recombinant
erythropoietin) within 4 weeks before randomization.

- Has received a live or live-attenuated vaccine within 30 days before the first dose of
study intervention.

- Has received investigational agent or has used an investigational device within 4
weeks prior to study intervention.

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

- Has a known additional malignancy that is progressing or has required active treatment
within the past 3 years.

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

- Has severe hypersensitivity (=Grade 3) to pembrolizumab, paclitaxel, or bevacizumab
(if using) and/or any of their excipients.

- Has an active autoimmune disease that has required systemic treatment in the past 2
years.

- Has a history of (noninfectious) pneumonitis/interstitial lung disease that required
steroids or has current pneumonitis/interstitial lung disease.

- Has an active infection requiring systemic therapy.

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

- Has a known history of Hepatitis B or known active Hepatitis C virus infection.

- Has a history or current evidence of any condition, therapy, laboratory abnormality,
or other circumstance that might confound the results of the study.

- Has a known psychiatric or substance abuse disorder that would interfere with the
participant's ability to cooperate with the requirements of the study.

- Participant, in the judgement of the investigator, is unlikely to comply with the
study procedures, restrictions, and requirements of the study.

- Has had an allogenic tissue/solid organ transplant.

For bevacizumab treatment

- Has uncontrolled hypertension.

- Has current, clinically relevant bowel obstruction including related to underlying
epithelial OC, abdominal fistula or gastrointestinal perforation, intra-abdominal
abscess, or evidence of rectosigmoid involvement by pelvic exam.

- Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active
gastrointestinal bleeding within 6 months before randomization.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s

The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
13/12/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/08/2027
Actual
Sample size
Target
616
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital-Department of Gynaecological Oncology ( Site 0201) - Westmead
Recruitment hospital [2] 0 0
Gallipoli Medical Research Foundation-GMRF CTU ( Site 0202) - Brisbane
Recruitment hospital [3] 0 0
Epworth Freemasons ( Site 0204) - Melbourne
Recruitment hospital [4] 0 0
St. John of God Subiaco Hospital ( Site 0203) - Subiaco
Recruitment postcode(s) [1] 0 0
2145 - Westmead
Recruitment postcode(s) [2] 0 0
4120 - Brisbane
Recruitment postcode(s) [3] 0 0
3002 - Melbourne
Recruitment postcode(s) [4] 0 0
6008 - Subiaco
Recruitment outside Australia
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United States of America
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Arizona
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California
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Connecticut
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Georgia
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Illinois
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Indiana
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Kentucky
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Louisiana
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Massachusetts
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New York
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North Carolina
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Ohio
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Oregon
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Pennsylvania
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South Dakota
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Tennessee
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Texas
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United States of America
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Virginia
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Belgium
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Bruxelles-Capitale, Region De
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Belgium
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Belgium
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Vlaams-Brabant
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Belgium
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Brazil
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Goias
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Rio Grande Do Norte
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Santa Catarina
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Sao Paulo
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Brazil
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Rio de Janeiro
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Alberta
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British Columbia
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Ontario
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Araucania
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Zhejiang
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Distrito Capital De Bogota
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Languedoc-Roussillon
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Bayern
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Saarland
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Sachsen
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Hamburg
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Dublin
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Afula
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Haifa
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Ramat Gan
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Tel Aviv
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Lombardia
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Italy
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Milano
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Italy
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Piemonte
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Italy
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Brescia
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Aichi
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Chiba
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Ehime
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Fukuoka
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Hokkaido
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Iwate
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Kanagawa
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Saitama
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Tokyo
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Osaka
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Seoul
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Baja California Sur
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Distrito Federal
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Mexico
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Nuevo Leon
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Mexico
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Oaxaca
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Netherlands
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Gelderland
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Zuid-Holland
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Netherlands
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Utrecht
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New Zealand
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Auckland
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Norway
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Troms
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Mazowieckie
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Podlaskie
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Pomorskie
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Slaskie
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Swietokrzyskie
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Poland
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Wielkopolskie
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Russian Federation
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Chelyabinskaya Oblast
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Russian Federation
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Mordoviya, Respublika
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Russian Federation
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Moskovskaya Oblast
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Russian Federation
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Moskva
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Russian Federation
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Sverdlovskaya Oblast
Country [123] 0 0
Turkey
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Adana
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Turkey
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Istanbul
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Turkey
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Izmir
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Turkey
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Ankara
Country [127] 0 0
United Kingdom
State/province [127] 0 0
Brighton And Hove
Country [128] 0 0
United Kingdom
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Cambridgeshire
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United Kingdom
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Cornwall
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United Kingdom
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Cumbria
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United Kingdom
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Dundee City
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United Kingdom
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England
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United Kingdom
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London, City Of
Country [134] 0 0
United Kingdom
State/province [134] 0 0
Cardiff

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
Merck Sharp & Dohme LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The primary objective is to compare pembrolizumab plus paclitaxel with or without bevacizumab
to placebo plus paclitaxel with or without bevacizumab, with respect to progression-free
survival (PFS) per Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 as assessed by
the investigator. The hypotheses are that pembrolizumab plus paclitaxel with or without
bevacizumab is superior to placebo plus paclitaxel with or without bevacizumab, with respect
to PFS per RECIST 1.1 as assessed by the investigator for participants with programmed cell
death ligand 1 (PD-L1) positive tumors (Combined Positive Score [CPS] =1) and that
pembrolizumab plus paclitaxel with or without bevacizumab is superior to placebo plus
paclitaxel with or without bevacizumab, with respect to PFS per RECIST 1.1 as assessed by the
investigator for all participants.
Trial website
https://clinicaltrials.gov/ct2/show/NCT05116189
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Medical Director
Address 0 0
Merck Sharp & Dohme LLC
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/ct2/show/NCT05116189