Platinum-resistant Recurrent Ovarian Cancer MedDRA version: 21.1 Level: PT Classification code 10066697 Term: Ovarian cancer recurrent System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Merck Sharp & Dohme LLC
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: A participant will be eligible for inclusion in the study if the participant meets the following criteria: 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. – Participants must have received at least 4 cycles but not more than 9 cycles of platinum-based therapy in first line. – Adjuvant ± neoadjuvant therapy is considered 1 line – Participants may have received a prior PARPi; this will not be considered a separate line of therapy if received in maintenance – Participants may have received a prior anti-PD-1/anti-PD-L1 therapy or bevacizumab; 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 – Hormonal therapy for OC (eg, tamoxifen, aromatase inhibitors etc.) will not count as a separate line of prior 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, and at least one of the following conditions applies: • Is not a WOCBP OR • Is a WOCBP and: - Uses a contraceptive method that is highly effective (with a failure rate of <1% per year), with low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle (abstinent on a long-term and persistent basis) during the intervention period and for at least the time needed to eliminate each study intervention after the last dose of study intervention 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 length of time required to continue contraception for each study intervention is as follows: -- Pembrolizumab: 120 days -- Paclitaxel (or docetaxel, if applicable): 180 days -- Bevacizumab (if administered): 180 days The investigator should evaluate the potential for contraceptive method failure (ie, noncompliance, recently initiated) in relationship to the first dose of study intervention. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. If the contraception requirements in the local label for any of the study interventions is more stringent than the requirements above, the local label requirements are to be followed. - Has a negative highly sensitive pregnancy test (urine or serum as required by local regulations) within 24 hours for urine or within 72 hours for serum before the first dose of study intervention. If a urine test cannot be confirmed as negative (eg, an ambiguous result), a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive. - Absta
Exclusion criteria
Exclusion criteria: The participant must be excluded from the study if the participant meets the following criteria: 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. 5. Has current, clinically relevant bowel obstruction (including subocclusive disease) including related to underlying epithelial OC, abdominal fistula or gastrointestinal perforation, intra-abdominal abscess, or evidence of rectosigmoid involvement by pelvic exam. 6. Has a history of thrombotic disorders, hemorrhage, hemoptysis, or active gastrointestinal bleeding within 6 months before randomization. 7. Has received >2 prior lines of systemic therapy for OC. 8. Has received prior systemic anticancer therapy, including investigational agents or maintenance therapy (including bevacizumab maintenance 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 (eg, G-CSF, GM-CSF or recombinant erythropoietin) within 4 weeks before randomization. 12. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines are allowed. 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 (dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive 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, (ie, without evidence of progression) for at least 4 weeks by repeat imaging, clinically stable and without requirement of steroid treatment for at least 14 days before the first dose of study intervention. 17. Has severe hypersensitivity (=Grade 3) to pembrolizumab, paclitaxel, or bevacizumab (if using) and/or any of their excipients. 18. Has an active autoimmune disease that has required systemic treatment in the past 2 years (ie, with use of disease modifying agents, corticosteroids, or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency) is not considered a form of systemic treatment and is allowed. 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 (defined as HBsAg reactive) or known active Hepatitis C virus (d
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: 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 RECIST 1.1 as assessed by the investigator;Secondary Objective: 1. To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab with respect to overall survival (OS) 2. To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab with respect to PFS per RECIST 1.1 by blinded independent central review (BICR) for PD-L1+ (CPS =1) and all participants 3. To evaluate safety and tolerability of pembrolizumab plus paclitaxel with or without bevacizumab 4. To compare pembrolizumab plus paclitaxel with or without bevacizumab to placebo plus paclitaxel with or without bevacizumab, with respect to Global Health Status/Quality of Life (GHS/QoL) score using European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 (QLQ-C30) and abdominal/gastrointestinal (GI) symptoms using EORTC Ovarian Cancer-Specific Quality of Life Questionnaire (QLQ-OV28) for PD-L1+ (CPS =1) and all participants ;Primary end point(s): 1. Progression-free Survival (PFS) per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) by Investigator;Timepoint(s) of evaluation of this end point: 1. Up to ~38 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1. Overall Survival (OS) 2. PFS per RECIST 1.1 by Blinded Independent Central Review (BICR) 3. Number of Participants who Experience an Adverse Event (AE) 4. Number of Participants who Discontinue Study Treatment due to an AE 5. 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) 6. Time to Deterioration (TTD) in the GHS/Qol Score (Items 29 and 30) Using the EORTC QLQ-C30 7. 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 8. TTD in the Abdominal and GI Symptoms Score (Items 31 to 36) Using the EORTC QLQ-OV28 Abdominal/GI Symptom Scale;Timepoint(s) of evaluation of this end point: 1. Up to ~64 months 2. Up to ~38 months 3. Up to ~64 months 4. Up to ~64 months 5. Baseline and up to ~64 months 6. Up to ~64 months 7. Baseline and up to ~64 months 8. Up to ~64 months | — |
Countries
Australia, Belgium, Brazil, Canada, Chile, China, Colombia, Denmark, Finland, France, Germany, Ireland, Israel, Italy, Japan, Korea, Democratic People's Republic of, Mexico, Netherlands, New Zealand, Norway, Poland, Russian Federation, Turkey, United Kingdom, United States
Outcome results
None listed