| Eligibility |
Inclusion Criteria:
- Able to provide written informed consent.
- Age =18 years or =20 years for Japanese participants.
- Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
- Life expectancy of =12 weeks
- Have histologically or cytologically-documented, locally-advanced, or metastatic solid
malignancy that is incurable and has either (a) failed prior standard therapy, (b) for
which no standard therapy exists, or (c) standard therapy is not considered
appropriate by the patient and treating physician.
- Have one of the following advanced (unresectable and/or metastatic) solid tumor
indications:
- Microsatellite Stable Colorectal Carcinoma (MSS-CRC)
- Platinum Resistant Epithelial Ovarian Cancer Type II (PR-OC)
- Estrogen Receptor Positive and HER2 Negative Breast Cancer (ER+/HER2- BC):
- The following considerations will be made regarding prior treatment regimens:
- MSS-CRC: must have progressed or be intolerant of 5-FU, irinotecan, oxaliplatin
and epidermal growth factor receptor (EGFR) mAb in patients with RAS wild type
tumors, in recurrent/metastatic setting.
- PR-OC: must have progressed on at least 1, maximum of 2 lines of cytotoxic agents
in the platinum resistant disease setting
- ER+/HER2- BC: must have progressed on at least 2, maximum of 5 lines of cytotoxic
agents in recurrent/metastatic setting.
- Adequate normal organ and marrow function
- Willing and able to comply with the protocol for the duration of the study including
undergoing treatment and scheduled visits and examinations including follow up.
- At least one measurable lesion according to RECIST v1.1.
- At least one lesion safely accessible for biopsy.
- Be willing to provide tissue from a newly obtained core or excisional biopsy of a
tumor lesion.
- Consent to provide archival tumor tissue (initial and subsequent tumor biopsy samples,
if possible) for correlative biomarker studies, if available.
- Female subject of childbearing potential1 should have two negative pregnancy tests as
verified by the investigator prior to starting any investigational product therapy
- Females of childbearing potential who are sexually active with a non-sterilized male
partner must agree to practice true abstinence or use at least two effective methods
of contraception for the study defined period.
- Non-sterilized males who are sexually active with a female partner of childbearing
potential must agree to use at least two effective methods of contraception for the
study defined period.
Exclusion Criteria:
- Involvement in the planning and/or conduct of the study or previous enrolment in the
present study.
- Participation in another clinical study with an investigational product during the
last 28 days or 5 half-lives prior to study Day 1. Concurrent enrolment in an
observational (noninterventional) clinical study or the follow-up period of an
interventional study is allowed.
- Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab. Prior
anti-CTLA4 agents are allowed. Prior therapy with T-cell co-stimulatory agents (e.g.
anti-CD137 antibody, anti-OX40 antibody) are allowed.
- Prior therapy with CC-486, azacitidine, decitabine or any other hypomethylating agent.
- History of another primary malignancy with exceptions.
- Receipt of the last dose of anti-cancer therapy (chemotherapy, immunotherapy,
endocrine therapy, targeted therapy, biologic therapy, tumor embolization, monoclonal
antibodies, other investigational agent) = 28 days prior to the first dose of study
drug (and within 6 weeks for nitrosourea or mitomycin C).
- Mean QT interval corrected for heart rate (QTc) =470 ms.
- Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab with exceptions.
- Any unresolved toxicity CTCAE grade 2 from previous anti-cancer therapy.
- Any prior Grade =3 immune-related adverse event (irAE) while receiving any previous
immunotherapy agent, or any unresolved irAE >Grade 1, with exception of chronic
endocrinopathy that is stable on hormone replacement.
- Active or prior documented autoimmune disease within the past 2 years.
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
ulcerative colitis).
- History of primary immunodeficiency
- History of allogeneic organ transplant
- History of hypersensitivity to study drug formulations, including azacitidine,
mannitol, or durvalumab, its constituents, or to any other humanized monoclonal
antibody
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active
infection, symptomatic congestive heart failure, uncontrolled hypertension, unstable
angina pectoris, cardiac arrhythmia, active peptic ulcer disease or gastritis, active
bleeding diatheses including any patient known to have evidence of acute or chronic
hepatitis B, hepatitis C or human immunodeficiency virus (HIV), or psychiatric
illness/social situations that would limit compliance with study requirements or
compromise the ability of the patient to give written informed consent
- Known history of previous clinical diagnosis of tuberculosis
- Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of investigational products.
- Female patients who are pregnant, breast-feeding or male or female patients of
reproductive potential who are not employing an effective method of birth control.
- Irritable bowel syndrome or other serious gastrointestinal chronic conditions
associated with diarrhea within the past 3 years prior to the start of treatment,
and/or history of prior gastrectomy or upper bowel removal, or any other
gastrointestinal disorder or defect that would interfere with the absorption,
distribution, metabolism or excretion of the investigational product and/or predispose
the patient to an increased risk of gastrointestinal toxicity.
- Untreated central nervous system (CNS) metastatic disease, leptomeningeal disease, or
cord compression.
- Patients with uncontrolled seizures.
- Any concurrent chemotherapy, immunotherapy, or biologic or hormonal therapy for cancer
treatment with the exception of patients on adjuvant endocrine therapy for a history
of non-invasive breast cancer.
- Major surgery within 28 days prior to Day 1 of the study or still recovering from
prior surgery.
- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results.
- Patients who are involuntarily incarcerated or are unable to willingly provide consent
or are unable to comply with the protocol procedures.
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