Pembrolizumab With Chemotherapy and MK-4830 for Treating Participants With Ovarian Cancer (MK-4830-002)
Study Details
Study Description
Brief Summary
The primary objective is to evaluate in participants with high-grade serous ovarian cancer (HGSOC), whether the reduction from baseline in circulating tumor DNA (ctDNA) at Cycle 3 (ΔctDNA) is larger in participants receiving MK-4830 + pembrolizumab in combination with standard of care (SOC) therapy than in those receiving pembrolizumab + SOC therapy.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Pembrolizumab + Standard of Care (SOC) + MK-4830 Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2, carboplatin Area Under the Curve (AUC) 5 to 6, (or docetaxel 75 mg/m^2), and MK-4830 800 mg by intravenous (IV) infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2, carboplatin AUC 5 to 6, (or docetaxel 75 mg/m^2), MK-4830 800 mg, and avastin (or biosimilar) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. |
Biological: Pembrolizumab
200 mg by IV infusion on Day 1 of each 21-day cycle
Other Names:
Drug: Paclitaxel
175 mg/m^2 by IV infusion on Day 1 of each 21-day cycle
Other Names:
Drug: Carboplatin
AUC 5 to 6 by IV infusion on Day 1 of each 21-day cycle
Other Names:
Biological: Avastin
According to local practice and at the choice of the investigator.
Other Names:
Biological: MK-4830
800 mg by IV infusion on Day 1 of each 21-day cycle
Drug: Docetaxel
75 mg/m^2 by IV infusion on Day 1 of each 21-day cycle
|
| Active Comparator: Pembrolizumab + SOC Before surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2, carboplatin AUC 5 to 6 and (or docetaxel 75 mg/m^2) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. After surgery participants will receive pembrolizumab 200 mg, paclitaxel 175 mg/m^2, carboplatin AUC 5 to 6, (or docetaxel 75 mg/m^2) and avastin (or biosimilar) by IV infusion on Day 1 of each 21-day cycle (Q3W) for 3 cycles. |
Biological: Pembrolizumab
200 mg by IV infusion on Day 1 of each 21-day cycle
Other Names:
Drug: Paclitaxel
175 mg/m^2 by IV infusion on Day 1 of each 21-day cycle
Other Names:
Drug: Carboplatin
AUC 5 to 6 by IV infusion on Day 1 of each 21-day cycle
Other Names:
Biological: Avastin
According to local practice and at the choice of the investigator.
Other Names:
Drug: Docetaxel
75 mg/m^2 by IV infusion on Day 1 of each 21-day cycle
|
Outcome Measures
Primary Outcome Measures
- Change from Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA) [Baseline and Week 7]
Change from baseline in circulating tumor deoxyribonucleic acid (ctDNA).
Secondary Outcome Measures
- Change from Baseline in Neoadjuvant ctDNA [Baseline and Week 7]
Change from baseline in neoadjuvant ctDNA.
- Pathological Complete Response (pCR) Rate [Up to approximately 12 weeks]
Percentage of participants with all surgical specimens collected during the interval debulking surgery that are microscopically negative for residual tumor by logistic regression modeling of pathological Complete Response (pCR).
- Chemotherapy Response Score (CRS) [Up to approximately 12 Weeks]
Percentage of participants with residual disease assessed by logistic regression modeling of chemotherapy response score (CRS). CRS is a 3-tiered scoring system (CRS 1-3) based on the pathological analysis of surgically removed omental masses, with CRS3 (complete or near-complete response) characterized by the lack of residual tumor cells in the omentum or presence of tumor foci up to 2 mm maximum size. A binary response of CRS3 (no residual disease) vs. non-CRS3 (residual disease) will be assessed.
- Number of Participants Who Experienced an Adverse Event (AE) [Up to approximately 40 Weeks]
An AE was any untoward medical occurrence in a participant administered study drug, which does not necessarily have to have a causal relationship with the study drug.
- Number of Participants Who Discontinued Study Treatment Due to an AE [Up to approximately 28 Weeks]
An AE was any untoward medical occurrence in a participant administered study drug which does not necessarily have to have a causal relationship with the study drug.
Eligibility Criteria
Criteria
The main inclusion and exclusion criteria include but are not limited to the following:
Inclusion Criteria:
-
Has histologically-confirmed International Federation of Gynecology and Obstetrics (FIGO) Stage III or Stage IV HGSOC, primary peritoneal cancer, or fallopian tube cancer.
-
Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the neoadjuvant and adjuvant setting.
-
Is a candidate for interval debulking surgery.
-
Is able to provide archival tissue or newly obtained core, incisional, or excisional biopsy of a tumor lesion.
-
Has adequate organ functions.
Exclusion Criteria:
-
Has a non-HGSOC histology.
-
Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease.
-
Has a known additional malignancy that is progressing or has required active treatment within the past 3 years.
-
Has received prior treatment for any stage of OC, including radiation or systemic anticancer therapy.
-
Planned or has been administered intraperitoneal chemotherapy as first-line therapy.
-
Has received prior therapy with an anti-programmed cell death 1 protein (PD-1), anti-programmed cell death 1 ligand 1 (PD-L1), anti-programmed cell death 1 ligand 2 (PD-L2), anti-immunoglobulin-like transcript 4 (ILT4), or anti-human leukocyte antigen (HLA)-G agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor.
-
Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention.
-
Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks before the first dose of study intervention.
-
Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication.
-
Has known active Central Nervous System (CNS) metastases and/or carcinomatous meningitis.
-
Has severe hypersensitivity to pembrolizumab, carboplatin, paclitaxel (or docetaxel, if applicable), Avastin or biosimilar (if using) and/or any of their excipients.
-
Has an active autoimmune disease that has required systemic treatment in past 2 years.
-
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 received colony-stimulating factors within 4 weeks prior to receiving study intervention on Day 1 of Cycle 1.
-
Has had surgery <6 months prior to Screening to treat borderline ovarian tumors, early-stage OC, or early-stage fallopian tube cancer.
-
Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
-
Has current, clinically relevant bowel obstruction.
-
Has a history of hemorrhage, hemoptysis, or active gastrointestinal (GI) bleeding within 6 months prior to randomization.
-
Has uncontrolled hypertension.
-
Has had an allogenic tissue/solid organ transplant.
-
.Has either had major surgery within 3 weeks of randomization or has not recovered from any effects of any major surgery.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Rutgers Cancer Institute of New Jersey ( Site 0114) | New Brunswick | New Jersey | United States | 08903 |
| 2 | Rambam Health Care Campus-Gyneco-oncology unit ( Site 0602) | Haifa | Israel | 3109601 | |
| 3 | Shaare Zedek Medical Center ( Site 0601) | Jerusalem | Israel | 9103102 | |
| 4 | Sheba Medical Center-ONCOLOGY ( Site 0600) | Ramat Gan | Israel | 5265601 | |
| 5 | Seoul National University Hospital ( Site 0801) | Seoul | Korea, Republic of | 03080 | |
| 6 | Severance Hospital, Yonsei University Health System-Gynecologic cancer center ( Site 0800) | Seoul | Korea, Republic of | 03722 | |
| 7 | Instituto Catalan de Oncologia - Hospital Duran i Reynals-Medical Oncology ( Site 1103) | Hospitalet | Barcelona | Spain | 08907 |
| 8 | Changhua Christian Hospital-Obstetrics and Gynecology ( Site 1203) | Changhua County | Changhua | Taiwan | 50006 |
| 9 | Taichung Veterans General Hospital-GYNECOLOGY ( Site 1202) | Taichung | Taiwan | 407 | |
| 10 | National Taiwan University Hospital-Internal Medicine ( Site 1200) | Taipei | Taiwan | 10002 |
Sponsors and Collaborators
- Merck Sharp & Dohme LLC
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.- 4830-002
- MK-4830-002
- 2021-005458-27