A Phase II, Open-label, Single-arm, Multicenter Study to Evaluate Efficacy and Safety of Pembrolizumab Monotherapy in Subjects with Advanced Recurrent Ovarian Cancer

Phase 2

Completed

Conditions: 10038594
Ovarian cancer

Registration Number: NL-OMON47631

Lead Sponsor: Merck Sharp & Dohme (MSD)

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 23

Inclusion Criteria

1. Be willing and able to provide written informed consent for the trial. The
subject may also provide consent for Future Biomedical Research. However, the
subject may participate in the main trial without participating in Future
Biomedical Research.
2. Be > or <= 18 years of age on day of signing informed consent.
3. Have histologically confirmed epithelial ovarian cancer, fallopian tube
cancer or primary peritoneal cancer
4. Have received a front line platinum-based regimen (administered via either
IV or IP route) per local SOC or treatment guideline following the primary or
interval debulking surgery with documented disease recurrence.
Note: Maintenance treatment following the front line treatment is permitted and
counted together as part of the front line treatment.
5. Have fulfilled the following additional requirements regarding prior
treatments for recurrent ovarian cancer (ROC) depending on the cohort subject
is to be enrolled. Each subject must have documented evidence of clinical
response or disease stabilization to the last regimen received.
Cohort A: Have received 0 to 2 additional prior lines for treating ROC (or 1-3
total prior lines counting the front line) and must have a platinum-free
interval (PFI) of > or <= 3 to 12 months if the last regimen received is a
platinum-based, or a treatment-free interval (TFI) of > or <= 3 to 12 months
if the last regimen received is a non-platinum-based.
Cohort B: Have received 3 to 5 additional prior lines for treating ROC (or 4-6
total prior lines counting the front line) and must have a PFI of > or <=3
months if the last regimen received is a platinum-based, or a TFI of > or <=
3 months if the last regimen received is a non-platinum-based.
Note: PFI is defined as the time elapsed between the last dose of platinum and
the documented evidence of disease progression per RECIST 1.1. TFI is defined
as the time elapsed between the last dose of the regimen received and the
documented evidence of disease progression per RECIST 1.1.
6. Have measurable disease at baseline based on RECIST 1.1 as determined by the
central imaging vendor.
Note: Tumor lesions situated in a previously irradiated area are considered
measurable if progression has been demonstrated in such lesions.
7. Have an ECOG performance status of 0 or 1
8. Have a life expectancy of > or <=16 weeks.
9. Have provided a tumor tissue sample either collected from prior
cytoreductive surgery or fresh newly obtained tumor tissue at screening.
Formalin-fixed paraffin-embedded (FFPE) block specimens are preferred to
slides. Additional samples may be requested if tumor tissue provided is not
adequate for quality and/or quantity as assessed by the central laboratory.
Note 1: Tumor tissue samples from recent biopsy are much preferred as it
represents the current disease status and is much more informative for
understanding the correlation between clinical activity and tumor
microenvironment.
If available, paired tumor tissue samples from prior cytoreductive surgery and
recent biopsy are strongly encouraged in order to understand the changes in
tumor microenvironment during the course of the treatments.
Note 2: For archival tumor tissue samples, block specimens are much preferred
than slides. If submitting unstained cut slides, freshly cu

Exclusion Criteria

1. Is currently participating in or has participated in a clinical study and
received an investigational agent or used an investigational device within 4
weeks prior to the first dose of study treatment.
Note: Subjects who have entered the follow-up phase of an investigational study
may participate as long as it has been 4 weeks since the last dose of the
previous investigational agent or device.
2. Has an active autoimmune disease that has required systemic treatment in the
past 2 years (i.e. 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.
3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy
or any other form of immunosuppressive therapy within 7 days prior to the
planned first dose of the study. The use of physiologic doses of
corticosteroids may be approved after consultation with the Sponsor.
4. Has had prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted
small molecule therapy, or radiation therapy within 4 weeks prior to the
planned first dose of the study
5. Has not recovered from adverse events to < or = Grade 1 or prior
treatment level due to a previously administered agent.
Note: Subjects with < or = Grade 2 neuropathy or alopecia of any grade are
an exception to this criterion and may qualify for the study.
Note: If subject received major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
therapy.
6. Has EOC with mucinous histology subtype. Or has a known additional
malignancy that progressed or required active treatment within the last 5
years. Exceptions include basal cell carcinoma of the skin, squamous cell
carcinoma of the skin that has undergone potentially curative therapy or in
situ cervical cancer.
7. Has known active central nervous system (CNS) metastases and/or
carcinomatous meningitis. Subjects with previously treated brain metastases may
participate provided they have stable brain metastases.
8. Has known history of, or any evidence of active, non-infectious pneumonitis.
9. Has an active infection requiring systemic therapy.
10. Has symptoms of bowel obstruction in the past three months
11. Has a history or current evidence of any condition, therapy, or laboratory
abnormality that might confound the results of the trial, interfere with the
subject*s participation for the full duration of the trial, or is not in the
best interest of the subject to participate, in the opinion of the treating
investigator.
12. Has known psychiatric or substance abuse disorders that would interfere
with cooperation with the requirements of the trial.
13. Is pregnant or breastfeeding, or expecting to conceive children within the
projected duration of the trial, starting with the screening visit through 120
days after the last dose of trial treatment.
14. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent
or with an agent directed to another co-inhibitory T-cell receptor (e.g.
CTLA-4, OX-40, CD137) or has participated in prior pembrolizumab trials.
15. Has a known history of Human Immunodeficien

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Primary objective (1) is to evaluate objective response rate (ORR) in the first<br /><br>180 enrolled subjects who fulfill the eligibility criteria for Cohort A.<br /><br>Primary objective (2) is to evaluate ORR in subjects who fulfill the<br /><br>eligibility criteria for Cohort A and with higher expression of program death<br /><br>ligand protein 1 (PD-L1) in tumor tissue samples.<br /><br>Primary objective (3) is to evaluate ORR in all enrolled subjects who fulfill<br /><br>the eligibility criteria for Cohort B.<br /><br>Primary objective (4) is to evaluate ORR in subjects enrolled into Cohort B who<br /><br>have tumor tissue PD-L1 expression above the clinical cutpoint established from<br /><br>the Cohort A training set.</p><br>

Secondary Outcome Measures