MK-4830-002 - A Randomized, Phase 2 Study of Pembrolizumab And Chemotherapy With or Without MK-4830 as Neoadjuvant Treatment for High-Grade Serous Ovarian Cancer

Studio Clinico

Patologia: Tumori dell’ovaio

Osservazionale-Sperimentale: Sperimentale

Monocentrico-Multicentrico: Multicentrico

Randomizzato: Sì

Fase di studio: II Randomizzato

Richiesta mandatoria di tessuto: Sì

Linee di trattamento: Adiuvante/neoadiuvante

Criteri di inclusione: 

1. Has histologically-confirmed FIGO Stage III or Stage IV HGSOC, primary peritoneal cancer, or fallopian tube cancer [Prat, J. and FIGO Committee on Gynecologic Oncology 2014].
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 [Vergote, I., et al 2010] 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. Details pertaining to tumor tissue submission requirements can be found in the laboratory manual.
Note: Prior to randomization, archival or newly obtained tissue at Screening must be confirmed to be of sufficient quality and quantity to analyze the primary endpoint (which requires tissue for analysis) by the designated laboratory. Participants will not be eligible for the study if it is not of sufficient quality and quantity, and they cannot provide an additional sample that meets the above criteria.
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 studyintervention 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 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), as
described in Appendix 5 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:
    ◦ MK-4830: 180 days
    ◦ Pembrolizumab: 120 days
    ◦ Chemotherapy: 180 days (refer to Appendix 7 for country-specific requirements)
    ◦ Avastin (or biosimilar 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 either 24 hours (urine) or 72 hours (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. Additional requirements for pregnancy testing during and after study intervention are in
Section 8.3.5.
    - 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.
Informed Consent
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 as defined in Table 1; all screening laboratory tests should be performed within 7 days prior to the first dose of study intervention on Day 1 of Cycle 1.

Criteri di esclusione: 

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.
Note: The time requirement does not apply to participants who underwent successful definitive resection of basal cell carcinoma of the skin, squamous-cell carcinoma of the skin, superficial bladder cancer, in-situ cervical cancer, or other in-situ cancers.
Note: Participants with synchronous primary endometrial cancer or a past history of primary endometrial cancer that meet the following conditions are not excluded: Stage not greater than IA; no more than superficial myometrial invasion, without vascular or lymphatic invasion; no poorly differentiated subtypes, including papillary serous, clear cell or other FIGO Grade 3 lesions.
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. Refer to Section 6.5 for information on COVID-19 vaccines.
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.
Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
9. 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.
Note: Participants that require intermittent use of non-systemic steroids such as ocular, inhaled, intranasal, topical steroids, or local steroid injections are not excluded from the study.
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 (Note: The repeat imaging should be performed during study screening.), clinically stable, and without requirement of steroid treatment for at least 14 days before the first dose of study intervention.
Note: Participants with known untreated, asymptomatic brain metastases (ie, no neurological symptoms, no requirement for corticosteroids, no or minimal surrounding edema, and no lesion >1.5 cm) may participate but will require imaging of the brain as a site of disease as specified in the SoA.
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.
Note: No HIV testing is required unless mandated by local health authority. Refer to Appendix 7 for country-specific requirements.
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.
Note: No testing for hepatitis B and hepatitis C is required unless mandated by local health authority. Participants with a history of hepatitis B but who are HBsAg negative are eligible for the study. Refer to Appendix 7 for country-specific requirements.
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 it is not in the best interest of the participant to participate, in the opinion of the treating investigator.
20. Has a known psychiatric or substance abuse disorder that would interfere with the participant's ability to cooperate with the requirements of the study.
21. Has current, clinically relevant bowel obstruction (including subocclusive disease), abdominal fistula, or GI perforation, related to underlying epithelial OC.
Note: This applies only to participants who will receive Avastin (or biosimilar) during Cycles 4 to 6 and should be confirmed prior to the first dose of Avastin (or biosimilar).
22. Has a history of hemorrhage, hemoptysis, or active GI bleeding within 6 months prior to randomization.
Note: This applies only to participants who will receive Avastin (or biosimilar) during Cycles 4 to 6 and should be confirmed prior to the first dose of Avastin (or biosimilar).
23. Has uncontrolled hypertension.
Note: This applies only to participants who will receive Avastin (or biosimilar) during Cycles 4 to 6 and should be confirmed prior to the first dose of Avastin (or biosimilar).
Use of antihypertensive medications to control blood pressure is permitted.
24. Has had an allogenic tissue/solid organ transplant.
25. Has either had major surgery within 3 weeks of randomization or has not recovered from any effects of any major surgery.
26. In the judgment of the investigator, is unlikely to comply with the study procedures, restrictions, and requirements of the study.

Trattamento sperimentale: 

MK-4830

Trattamento di controllo: 

Carbo + Pacli + Pembro

Centri partecipanti

Nord Italia

Centro Italia

Sud Italia e isole

Informazioni Generali

Protocollo

Numero di iscrizione a registro: 2021-005458-27

Data di inserimento: 29.09.2023

Promotore

Merck Sharp & Dohme LLC

Principal Investigator ITALIA

Fonfazione Policlinico universitario Agostino Gemelli - Ginecologia Oncologica

Riferimento: Prof.ssa Domenica Lorusso

Telefono: 00000

Email: domenica.lorusso@policlinicogemelli.it

Localita: Roma