| Eligibility |
Inclusion Criteria:
1. Be willing and able to provide written informed consent/assent for the trial. The
subject may also provide consent/assent for Future Biomedical Research. However, the
subject may participate in the main trial without participating in Future Biomedical
Research
2. Be >18 years of age on day of signing informed consent.
3. Have a histologically or cytologically-documented, advanced (metastatic and/or
unresectable) endometrial carcinoma that is incurable and for which prior
platinum-based chemotherapy for first-line treatment has failed. All epithelial
endometrial histologies are eligible including: endometrioid, serous, clear-cell
carcinoma, squamous or carcinosarcoma. Sarcomas and mesenchymal tumors are excluded.
4. Eligible subjects must have had only 1 prior line of systemic platinum-based
chemotherapy for advanced, recurrent or metastatic endometrial cancer. Patients who
have had 2 or more prior chemotherapeutic regimens for advanced, recurrent, or
metastatic endometrial cancer are not allowed.
Note: Prior neoadjuvant or adjuvant chemotherapy included in initial treatment may not
be considered first- or later-line treatment unless such treatments were completed
less than 6 months prior to the current tumor recurrence. Prior treatment may include
chemotherapy, chemotherapy/radiation therapy, and/or consolidation/maintenance
therapy.
Prior hormonal treatment is not considered a line of therapy in any setting. Prior
targeted therapy no directed against PD-1, PD-L1, PD-L2 pathway or any other
immunemodulating mAb (including ipilimumab and any other antibody or drug specifically
targeting T-cell co-stimulation or checkpoint pathways) are allowed.
5. Have measurable disease based on RECIST 1.1, defined as at least 1 lesion that can be
accurately measured in at least 1 dimension (longest diameter to be recorded). Each
lesion must be = 10 mm in long axis when measured by CT, MRI, or caliper measurement
by clinical exam. Lymph nodes must be = 15 mm in short axis when measured by CT or
MRI. Tumor lesions situated in a previously irradiated area are considered measurable
if progression according to RECIST 1.1 criteria has been demonstrated in such lesions.
Patients must have radiographic evidence of disease progression following the most
recent line of treatment. Areas of previous radiation may not serve as measurable
disease unless there is evidence of progression post radiation according to RECIST 1.1
criteria. Patients with only one area of measureable disease that consent to have it
biopsied are still eligible.
6. Availability of fresh or archival FFPE tumor specimens for analysis for biomarker
analysis from a tumor lesion not previously irradiated (exceptions may be considered
after Sponsor consultation). (See Procedure Manual for detailed instructions). Be
willing to provide tissue from a newly obtained core or excisional biopsy of a tumor
lesion if archival specimen is not available. Newly-obtained is defined as a specimen
obtained up to 4 weeks (28 days) prior to initiation of treatment on Day 1.
7. Have a performance status of 0 or 1 on the ECOG Performance Scale.
8. Demonstrate adequate organ function as defined in Table 2, all screening labs should
be performed within 7 days of treatment initiation.
9. Female subject of childbearing potential should have a negative urine or serum
pregnancy 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. Female subjects of childbearing potential (Section 5.7.3) must be
willing to use an adequate method of contraception as outlined in Section 5.7.2 -
Contraception, for the course of the study through 120 days after the last dose of
study medication.
Exclusion Criteria:
1. Is currently participating and receiving study therapy or has participated in a study
of an investigational agent and received study therapy or used an investigational
device within 4 weeks of the first dose of treatment.
2. Receipt of 2 or more prior chemotherapy regimens for advanced, recurrent, or
metastatic endometrial cancer
3. History of myocardial infarction, acute inflammatory heart disease, unstable angina,
or uncontrolled arrhythmia within the past 6 months.
4. Impaired cardiac function defined as left ventricular ejection fraction (LVEF) < 50 %
(or below the study site's lower limit of normal) as measured by MUGA or ECHO. Planned
concomitant use of potentially cardiotoxic medication.
5. Previous anthracycline-based chemotherapy.
6. Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to the first dose of trial
treatment.
7. Has a known history of active TB (Bacillus Tuberculosis)
8. Hypersensitivity to pembrolizumab, doxorubicin or any of its excipients.
9. Has had a prior anti-cancer monoclonal antibody (mAb) within 4 weeks prior to study
Day 1 or who has not recovered (i.e., = Grade 1 or at baseline) from adverse events
due to agents administered more than 4 weeks earlier.
10. Has had prior chemotherapy, targeted small molecule therapy, or radiation therapy
within 4 weeks prior to study Day 1 or who has not recovered (i.e., = Grade 1 or at
baseline) from adverse events due to a previously administered agent. Note: Subjects
with = Grade 2 neuropathy are an exception to this criterion and may qualify for the
study. Note: If subject received major surgery, they must have recovered adequately
from the toxicity and/or complications from the intervention prior to starting
therapy. Note: Palliative radiotherapy within 2 weeks prior to study is allowed
provided that the site being treated is not subsequently used as a target lesions as
per RECIST v.1.1 for the purpose of assessing tumor response on trial.
11. Has a known additional malignancy that is progressing or requires active treatment.
Exceptions include basal cell carcinoma of the skin or squamous cell carcinoma of the
skin that has undergone potentially curative therapy or in situ cervical cancer.
12. Has known active central nervous system (CNS) metastases and/or carcinomatous
meningitis. Subjects with previously treated brain metastases may participate provided
they are stable (without evidence of progression by imaging for at least four weeks
prior to the first dose of trial treatment and any neurologic symptoms have returned
to baseline), have no evidence of new or enlarging brain metastases, and are not using
steroids for at least 7 days prior to trial treatment. This exception does not include
carcinomatous meningitis which is excluded regardless of clinical stability.
13. Has active autoimmune disease that has required systemic treatment in the past 2 years
(i.e. 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, etc.) is not considered a
form of systemic treatment.
14. Has a history of (non-infectious) pneumonitis that required steroids or current
pneumonitis.
15. Has an active infection requiring systemic therapy.
16. 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.
17. Has known psychiatric or substance abuse disorders that would interfere with
cooperation with the requirements of the trial.
18. Is pregnant or breastfeeding, or expecting to conceive within the projected duration
of the trial, starting with the pre-screening or screening visit through 120 days
after the last dose of trial treatment.
19. Has previously participated in any other pembrolizumab (MK-3475) trial, or received
prior therapy with an anti-PD-1, anti-PD-L1, anti-PD-L2, or any other immunemodulating
mAb (including ipilimumab and any other antibody or drug specifically targeting T-cell
co-stimulation or checkpoint pathways)
20. Has a known history of human immunodeficiency virus (HIV) infection. No HIV testing is
required unless mandated by local health authority. Has a known history of or is
positive for hepatitis B (hepatitis B surface antigen [HBsAg] Note: Without known
history, testing needs to be performed to determine eligibility. Hepatitis C antibody
(Ab) testing is allowed for screening purposes in countries where HCV RNA is not part
of standard of care.
21. Has received a live vaccine within 30 days of planned start of study therapy. Note:
Seasonal influenza vaccines for injection are generally inactivated flu vaccines and
are allowed; however intranasal influenza vaccines (e.g., Flu-Mist®) are live
attenuated vaccines, and are not allowed.
22. Any other condition that would, in the Investigator's judgment, contraindicate the
patient's participation in the clinical study due to safety concerns or compliance
with clinical study procedures, e.g., infection/inflammation, social/ psychological
issues.
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