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)
- Conditions
- Ovarian CancerOvarian carcinoma10033283
- Registration Number
- NL-OMON51981
- Lead Sponsor
- Merck Sharp & Dohme (MSD)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Recruiting
- Sex
- Not specified
- Target Recruitment
- 14
The below-mentioned inclusion criteria are the most important ones. A complete
list of cohort specific inclusion criteria can be found in the protocol.
1. Has histologically confirmed epithelial (including high-grade serous or
predominantly
serous, low-grade serous, any-grade endometrioid, malignant mixed Müllerian
tumors
[carcinosarcoma], or clear cell) ovarian, fallopian tube, or primary peritoneal
carcinoma.
2. Has received 1 or 2 prior lines of systemic therapy for OC, including at
least 1 prior
platinum-based therapy.
3. Has radiographic evidence of disease progression within 6 months (180 days)
after the
last dose of platinum-based chemotherapy for OC (ie, platinum-resistant
disease).
4. Is a candidate for paclitaxel chemotherapy (and bevacizumab, if using).
5. Is female, and at least 18 years of age, at the time of signing the informed
consent.
6. Has an ECOG performance status of 0 to 1 assessed within 3 days before
randomization.
7. A female participant is eligible to participate if she is not pregnant or
breastfeeding
8. The participant (or legally acceptable representative) has provided
documented informed
consent for the study
9. Has radiographically evaluable disease
10. Archival tumor tissue sample or newly obtained core or
incisional/excisional biopsy of a
tumor lesion not previously irradiated has been provided
11. Have adequate organ function
The below-mentioned exclusion criteria are the most important ones. A complete
list of cohort specific exclusion criteria can be found in the protocol.
1. Has nonepithelial cancers (germ cell tumors and sex cord-stromal tumors),
borderline
tumors (low malignant potential), mucinous, seromucinous that is predominantly
mucinous, malignant Brenner*s tumor and undifferentiated carcinoma.
2. 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.
3. Has prior disease progression on weekly paclitaxel alone.
4. Has uncontrolled hypertension. Note: only for patients receiving bevacizumab
5. Has current, clinically relevant bowel obstruction. Note: only for patients
receiving bevacizumab
6. Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active
gastrointestinal
bleeding within 6 months before randomization.Note: This applies only to
participants who will receive bevacizumab.
7. Has received >2 prior lines of systemic therapy for OC
8. Has received prior systemic anticancer therapy, including investigational
agents or maintanance therapy (including bevacizumab maintanance therapy) within
4 weeks before randomization
9. Has received prior radiation therapy within 2 weeks of start of study
intervention.
10. Has not recovered adequately from surgery and/or any complications from the
surgery.
11.Has received colony-stimulating factors within 4 weeks before randomization.
12. Has received a live or live-attenuated vaccine within 30 days before the
first dose of
study intervention
13. Has received an investigational agent or
has used an investigational device within 4 weeks prior to study intervention
administration.
14. Has a diagnosis of immunodeficiency or is receiving chronic systemic
steroid therapy within 7 days before the first dose of study medication.
15. Has a known additional malignancy that is progressing or has required
active treatment
within the past 3 years.
16. Has known active CNS metastases and/or carcinomatous meningitis.
Participants with
previously treated brain metastases may participate provided they are
radiologically stable
17. Has severe hypersensitivity (>=Grade 3) to pembrolizumab, paclitaxel, or
bevacizumab
18. Has an active autoimmune disease that has required systemic treatment in
the past 2 years
19. Has a history of (noninfectious) pneumonitis/interstitial lung disease that
required
steroids or has current pneumonitis/interstitial lung disease.
20. Has an active infection requiring systemic therapy
21. Has a known history of HIV infection.
22. Has a known history of Hepatitis B or known active Hepatitis C virus
23. Has a history or current evidence of any condition, therapy, laboratory
abnormality, or other circumstance that might confound the results of the study
or interfere with the participant's participation for the full duration of the
study
24. Has a known psychiatric or substance abuse disorder that would interfere
with the participant's ability to cooperate with the requirements of the study.
25. Participant, in the judgement of the investigator, is unlikely to comply
with the study procedures, restrictions, and requirements of the study.
26. Has had an
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method <p>Primary: To compare pembrolizumab plus paclitaxel with or without bevacizumab<br /><br>to placebo plus paclitaxel with or without bevacizumab, with<br /><br>respect to progression-free survival (PFS) per RECIST 1.1 as assessed by the<br /><br>investigator</p><br>
- Secondary Outcome Measures
Name Time Method <p>Secondary:<br /><br>- To compare pembrolizumab plus paclitaxel with or without bevacizumab to<br /><br>placebo plus paclitaxel with or without bevacizumab, with<br /><br>respect to overall survival (OS)<br /><br>- To compare pembrolizumab plus paclitaxel with or without bevacizumab to<br /><br>placebo plus paclitaxel with or without bevacizumab, with respect to<br /><br>progression free survival (PFS)<br /><br>- To evaluate the safety and tolerability of pembrolizumab in combination with<br /><br>paclitaxel with or without bevacizumab<br /><br>- To compare pembrolizumab plus paclitaxel with or without bevacizumab to<br /><br>placebo plus paclitaxel with or without bevacizumab, with respect to Global<br /><br>Health Status/Quality of Life (GHS/QoL) score</p><br>