Pembrolizumab in Subjects with Advanced Recurrent Ovarian Cancer

Phase 1

• Conditions: A: Platinum-resistant or partially platinum-sensitive recurrent ovarian cancer (OC) who received 1 but no more than 3 prior lines of anticancer regimens/local standard following primary or interval debulking surgery with a platinum free interval or treatment-free interval of 3-12months based on last regimen receivedB: Recurrent OC who received 3-5 prior lines of anticancer regimens/local standard with a platinum-free interval or treatment-free interval >or=3months based on last regimen received; MedDRA version: 21.1Level: PTClassification code 10070908Term: Ovarian cancer stage IVSystem Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps); Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2015-003338-29-IT
• Lead Sponsor: MERCK SHARP & DOHME CORP. UNA SUSSIDIARIA DI MERCK & CO. INC.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2021-01-18
• Last Update Posted: 5 April 2021

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: Female
• Target Recruitment: 378

Inclusion Criteria

1. Be willing and able to provide written informed consent for the trial. The subject may also provide consent for Future Biomedical Research. However, the subject may participate in the main trial without participating in Future Biomedical Research.
2. Be > or = 18 years of age on day of signing informed consent.
3. Have histologically confirmed epithelial ovarian cancer, fallopian tube cancer or primary peritoneal cancer
4. Have received a front line platinum-based regimen (administered via either IV or IP route) per local standard of care or treatment guideline following the primary or interval debulking surgery with documented disease recurrence.
5. Have fulfilled the following additional requirements regarding prior treatments for recurrent ovarian cancer (ROC) depending on the cohort subject is to be enrolled. Each subject must have documented evidence of clinical response or disease stabilization to the last regimen received.
Cohort A: Have received 0 to 2 additional prior lines for treating ROC (or 1-3 total prior lines counting the front line) and must have a platinum-free interval (PFI) of > or = 3 to 12 months if the last regimen received is a platinum-based, or a treatment-free interval (TFI) of > or = 3 to 12 months if the last regimen received is a non-platinum-based.
Cohort B: Have received 3 to 5 additional prior lines for treating ROC (or 4-6 total prior lines counting the front line) and must have a PFI of > or =3 months if the last regimen received is a platinum-based, or a TFI of > or = 3 months if the last regimen received is a non-platinum-based.
6. Have measurable disease at baseline based on RECIST 1.1 as determined by the central imaging vendor.
7. Have an ECOG performance status of 0 or 1
8. Have a life expectancy of > or =16 weeks.
9. Have provided a tumor tissue sample either collected from prior cytoreductive surgery or fresh newly obtained tumor tissue at screening. Formalin-fixed paraffin-embedded (FFPE) block specimens are preferred to slides. Additional samples may be requested if tumor tissue provided is not adequate for quality and/or quantity as assessed by the central laboratory.
10. Have demonstrated adequate organ function as defined in Table 1 of the protocol. All screening labs should be performed within 10 days of treatment initiation.
11. Female subjects of childbearing potential (see Section 5.7.1) must be willing to use an adequate method of contraception as outlined in Section 5.7.1 – Contraception, for the course of the study through 120 days after the last dose of study medication. Note: Abstinence is acceptable if this is the usual lifestyle and preferred contraception for the subject.
12. Female subjects of childbearing potential must have a negative urine or serum pregnancy test within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required.

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 195
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 130

Exclusion Criteria

1. Is currently participating in or has participated in a clinical study and received an investigational agent or used an investigational device within 4 weeks prior to the first dose of study treatment.
2. Has an active autoimmune disease that has required systemic treatment in the past 2 years (i.e. use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy
(e.g., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment.
3. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the planned first dose of the study. The use of physiologic doses of corticosteroids may be approved after consultation with the Sponsor.
4. Has had prior anti-cancer monoclonal antibody (mAb), chemotherapy, targeted small molecule therapy, or radiation therapy within 4 weeks
prior to the planned first dose of the study.
5. Has not recovered from adverse events to < or = Grade 1 or prior treatment level due to a previously administered agent.
6. Has EOC with mucinous histology subtype.
7. Has a known additional malignancy that progressed or required active treatment within the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin that has undergone potentially curative therapy or in situ cervical cancer.
8. Has known active central nervous system (CNS) metastases and/or
carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they have stable brain metastases.
9. Has known history of, or any evidence of active, non-infectious pneumonitis.
10. Has an active infection requiring systemic therapy.
11. Has symptoms of bowel obstruction in the past three months
12. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator.
13. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
14. Is pregnant or breastfeeding, or expecting to conceive children within the projected duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.
15. Has received prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2 agent or with an agent directed to another co-inhibitory T-cell receptor
(e.g. CTLA-4, OX-40, CD137) or has participated in prior pembrolizumab trials.
16. Has a known history of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies).
17. Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected).
18. Has received a live vaccine within 30 days of the planned first dose of the study.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified