A Randomized, Phase 2 Study of Pembrolizumab And Chemotherapy With or Without MK-4830 as Neoadjuvant Treatment for High Grade Serous Ovarian Cancer
- Conditions
- First-line treatment of advanced High Grade Serous Ovarian CancerMedDRA version: 20.0Level: PTClassification code 10033128Term: Ovarian cancerSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2021-005458-27-ES
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- Female
- Target Recruitment
- 160
1. Has histologically-confirmed FIGO Stage III or Stage IV HGSOC, primary peritoneal cancer, or fallopian tube cancer
2. Is a candidate for carboplatin and paclitaxel chemotherapy, to be administered in the neoadjuvant and adjuvant setting
3. Is a candidate for interval debulking surgery
4. Has either a CA-125 (kilounits/L):CEA (ng/mL) ratio =25 or, if the CA-125:CEA ratio is <25, then a workup should be negative for the presence of a non-OC tumor (eg, breast or GI cancers including CRC)
5. Is able to provide archival tissue or newly obtained core, incisional, or excisional biopsy of a tumor lesion
6. Is female and at least 18 years of age on the day of providing documented informed consent
7. Has an ECOG PS of 0 or 1, as assessed within 7 days prior to the first dose of study intervention on Day 1 of Cycle 1
8. 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 low user dependency, or be abstinent from heterosexual intercourse as their preferred and usual lifestyle, 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 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:
? MK-4830: 180 days
? Pembrolizumab: 120 days
? Chemotherapy: 180 days
? Avastin (or biosimilar if administered): 120 days
The investigator should evaluate the potential for contraceptive method failure 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 within either 24 hours (urine) or 72 hours (serum) before the first dose of study intervention. If a urine test cannot be confirmed as negative, a serum pregnancy test is required. In such cases, the participant must be excluded from participation if the serum pregnancy result is positive
- Has had her medical history, menstrual history, and recent sexual activity reviewed by the investigator to decrease the risk for inclusion of a woman with an early undetected pregnancy
9.The participant (or legally acceptable representative) has provided documented informed consent for the study. The participant may also provide consent for FBR. However, the participant may participate in the study without participating in FBR
10. Has an adequate organ function; all screening laboratory tests should be performed within 7 days prior to the first dose of study intervention on Day 1 of Cycle 1
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 60
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 100
1. Has a non-HGSOC histology
2. Has a history of (noninfectious) pneumonitis/interstitial lung disease that required steroids or has current pneumonitis/interstitial lung disease
3 .Has a known additional malignancy that is progressing or has required active treatment within the past 3 years
4. Has received prior treatment for any stage of OC, including radiation or systemic anticancer therapy (eg, chemotherapy, hormonal therapy, immunotherapy, investigational therapy)
5. Is a participant for whom intraperitoneal chemotherapy is planned or has been administered as first-line therapy
6. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-ILT4, or anti-HLA-G agent or with an agent directed to another stimulatory or coinhibitory T-cell receptor (eg, CTLA-4, OX-40, CD137) or MDSC-directed therapy
7. Has received a live or live-attenuated vaccine within 30 days before the first dose of study intervention. Administration of killed vaccines is allowed
8. 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
9. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (indosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior the first dose of study medication
10. 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
11. Has resting ECG indicating uncontrolled, potentially reversible cardiac conditions, as judged by the investigator (eg, unstable ischemia, uncontrolled symptomatic arrhythmia, congestive heart failure, QTcF prolongation >500 msec, electrolyte disturbances, etc.), or participant has congenital long QT syndrome
12. Has severe hypersensitivity (=Grade 3) to pembrolizumab, carboplatin, paclitaxel (or docetaxel, if applicable), Avastin or biosimilar (if using) and/or any of their excipients
13. Has an active autoimmune disease that has required systemic treatment in 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
14. Has an active infection, requiring systemic therapy
15. Has a known history of HIV infection
16. Has a known history of hepatitis B (defined as HBsAg reactive) or known active hepatitis C virus (defined as HCV RNA [qualitative] is detected) infection
17. Has received colony-stimulating factors (eg, G-CSF, GM-CSF, or recombinant erythropoietin) within 4 weeks (28 days) prior to receiving study intervention on Day 1 of Cycle 1
18. Has had surgery <6 months prior to Screening to treat borderline ovarian tumors, early-stage OC, or early-stage fallopian tube cancer
19. 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, such that
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Main Objective: 1. Among patients with detectable ctDNA at baseline, to evaluate whether the reduction from baseline in circulating tumor DNA at Cycle 3 (?ctDNA) is larger in participants receiving MK-4830 + pembrolizumab in combination with standard of care (SOC) chemotherapy than in those receiving pembrolizumab + SOC.;Secondary Objective: 1. Among patients with detectable ctDNA at baseline, to evaluate the association between neoadjuvant ?ctDNA at Cycle 3 from baseline and surgical outcomes<br>2. To estimate the difference in pCR and CRS following neoadjuvant treatment between arms<br>3. To evaluate the safety and tolerability of MK-4830 administered with pembrolizumab and chemotherapy;Primary end point(s): 1. Change from Baseline in Circulating Tumor Deoxyribonucleic Acid (ctDNA);Timepoint(s) of evaluation of this end point: 1. Baseline and Week 7
- Secondary Outcome Measures
Name Time Method Secondary end point(s): 1. Change from Baseline in Neoadjuvant ctDNA<br>2. Pathological Complete Response (pCR) Rate<br>3. Chemotherapy Response Score (CRS)<br>4. Number of Participants Who Experienced an Adverse Event (AE)<br>5. Number of Participants Who Discontinued Study Treatment Due to an AE;Timepoint(s) of evaluation of this end point: 1. Baseline and Week 7<br>2. Up to approximately 12 Weeks<br>3. Up to approximately 12 Weeks<br>4. Up to approximately 40 Weeks<br>5. Up to approximately 28 Weeks