| Eligibility |
Inclusion Criteria:
- Written informed consent
- Willingness and ability to comply with the protocol for the duration of the study
- Histologically confirmed intermediate or high grade adult-type soft tissue sarcoma
- Location of tumor is trunk (non-retroperitoneal) or extremities
- Tumor at least 5 cm in greatest dimension and deep to fascia, or locally recurrent, or
metastatic, or have had prior inadequate resections
- Judged as at least marginally resectable
- Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Adequate normal organ and marrow function
- Female subjects must be either of non-reproductive potential (i.e., post-menopausal by
history: =60 years old and no menses for =1 year without an alternative medical cause;
OR history of hysterectomy, OR history of bilateral tubal ligation, OR history of
bilateral oophorectomy) or must have a negative serum pregnancy test upon study entry.
- Females of childbearing potential who are sexually active with a non-sterilized male
partner and non-sterilized male subjects who are sexually active with a female partner
of childbearing potential must be willing to use 2 methods of effective contraception
from time of screening through 180 days after receipt of the final dose of Durvalumab
+ Tremelimumab combination therapy or 90 days after receipt of the final dose of
Durvalumab Monotherapy, whichever is the longer time period.
Exclusion Criteria:
- Primarily bone-based sarcomas that can occur in the soft tissue such as:
extra-skeletal Ewing sarcoma, extra-skeletal osteosarcoma, peripheral chordoma,
extra-skeletal myxoid chondrosarcoma, and mesenchymal chondrosarcoma
- Predominantly low-grade soft tissue sarcoma, such as solitary fibrous tumor /
hemangiopericytoma, well-differentiated liposarcoma, dermatofibrosarcoma protuberans,
Kaposi's sarcoma
- Pediatric-type soft tissue sarcoma, such as rhabdomyosarcoma
- Gastrointestinal stromal tumors (GIST)
- Retroperitoneal soft tissue sarcoma
- Patients with extra-pulmonary metastases aside from lymph node involvement
- Surgically unresectable primary lesion
- Symptomatic or uncontrolled brain metastases requiring concurrent treatment, inclusive
of but not limited to surgery, radiation and/or corticosteroids.
- Any previous treatment with an anti-PD-1 (programmed cell death protein-1), anti-PD-L1
(programmed death ligand 1) or anti-CTLA-4 (cytotoxic T-lymphocyte-associated protein
4) therapy, including Durvalumab and Tremelimumab
- History of hypersensitivity to Durvalumab or any excipient
- History of hypersensitivity to Tremelimumab or any excipient
- History of hypersensitivity to the combination or comparator agent
- History or clinically confirmed pneumonitis or interstitial lung disease
- Receipt of the last dose of anti-cancer therapy (cytotoxic 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 (28 days prior to the first dose of study drug for
subjects who have received prior TKIs (tyrosine kinase inhibitors) [e.g., erlotinib,
gefitinib and crizotinib] and within 6 weeks for nitrosourea or mitomycin C [If
sufficient wash-out time has not occurred due to the schedule or PK properties of an
agent, a longer wash-out period may be required])
- Current or prior use of immunosuppressive medication within 28 days before the first
dose of durvalumab or tremelimumab, with the exceptions of intranasal and inhaled
corticosteroids or systemic corticosteroids at physiological doses, which are not to
exceed 10 mg/day of prednisone, or an equivalent corticosteroid
- Any unresolved toxicity (>grade 2) from previous anti-cancer therapy. NOTE: Subjects
with irreversible toxicity that is not reasonably expected to be exacerbated by the
investigational product may be included (e.g., hearing loss, peripherally neuropathy)
- Any prior immune-related adverse event (irAE) = Grade 2 while receiving any previous
immunotherapy agent, or any unresolved irAE > Grade 1
- Active or prior documented autoimmune disease within the past 2 years. NOTE: Subjects
with vitiligo, Grave's disease, or psoriasis not requiring systemic treatment (within
the past 2 years) are not excluded.
- History of primary immunodeficiency
- History of allogeneic organ transplant (e.g. solid organ/bone marrow transplant
patients)
- Uncontrolled intercurrent illness including, but not limited to:
- Ongoing or active infections
- Cardiac conditions, such as:
- symptomatic congestive heart failure
- uncontrolled hypertension
- unstable angina pectoris
- cardiac arrhythmia
- Active peptic ulcer disease or gastritis
- History of inflammatory bowel disease, ulcerative colitis or Crohn's Disease
- Active bleeding diatheses
- Any subject known to have evidence of acute or chronic hepatitis B or hepatitis C
- Any subject known to have evidence of human immunodeficiency virus (HIV) or acquired
immune deficiency syndrome (AIDS)
- Uncontrolled seizures
- Mean QT interval corrected for heart rate (QTc) =470 ms calculated from 3
electrocardiograms (ECGs) using Fredericia's Correction
- Known history of current or recent clinical diagnosis of tuberculosis (within three
months prior to enrollment)
- Active or prior documented inflammatory bowel disease (e.g., Crohn's disease,
ulcerative colitis)
- Any signs or symptoms of bowel obstruction within 28 days prior to study entry
- History of leptomeningeal carcinomatosis
- Receipt of live attenuated vaccination within 30 days prior to study entry or within
30 days of receiving durvalumab or tremelimumab, or active infection
- History of psychiatric illness/social situations that would limit compliance with
study requirements or compromise the ability of the subject to give written informed
consent
- Any condition that, in the opinion of the investigator, would interfere with
evaluation of study treatment or interpretation of patient safety or study results
- Previously enrolled in the present study
- Participation in another clinical study with an investigational product during the
last 6 months
- Previously enrolled in the present study
- Involvement in the planning and/or conduct of the study (applies to both AstraZeneca
staff and/or staff at the study site)
- Female patients who are pregnant or breastfeeding or male or female patients of
reproductive potential who are not willing to employ effective birth control from
screening to 180 days after the last dose of durvalumab + tremelimumab combination
therapy or 90 days after the last dose of durvalumab monotherapy, whichever is the
longer time period
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