- Newly diagnosed biopsy proven The International Federation of Gynecology and
Obstetrics (FIGO) clinical stage I or II endometrial carcinoma.
- Histology of FIGO grade 1-3 endometrioid endometrial carcinoma.
- Medically inoperable per treating gynecologic oncologist.
- Candidate for definitive radiation therapy as determined by treating radiation
- At least 18 years of age.
- Eastern Cooperative Oncology Group (ECOG) performance status ≤ 2
- Participant must have adequate organ function, defined as follows:
- Absolute neutrophil count ≥ 1,500/µL
- Platelets ≥ 100,000/µL
- Hemoglobin ≥ 9 g/dL; transfusion is allowed to meet this criterion
- Serum creatinine ≤ 1.5 x upper limit of normal (ULN) or calculated creatinine
clearance 60mL/min using the Cockcroft-Gault equation
- Total bilirubin ≤ 1.5 x ULN (≤2.0 in patients with known Gilberts syndrome) OR
direct bilirubin ≤ 1 x ULN
- Aspartate aminotransferase and alanine aminotransferase ≤ 2.5 x ULN unless liver
metastases are present, in which case they must be ≤ 5 x ULN
- International normalized ratio (INR) or prothrombin time (PT) ≤1.5× ULN unless
patient is receiving anticoagulant therapy as long as PT or partial
thromboplastin (PTT) is within therapeutic range of intended use of
anticoagulants. Activated partial thromboplastin time (aPTT) ≤1.5× ULN unless
patient is receiving anticoagulant therapy as long as PT or PTT is within
therapeutic range of intended use of anticoagulants
- Participant receiving corticosteroids may continue as long as their dose is stable for
at least 4 weeks prior to initiating protocol therapy.
- Participant must agree to not donate blood during the study or for 90 days after the
last dose of study treatment.
- Female participant has a negative serum pregnancy test the day of and prior to taking
study treatment if of childbearing potential and agrees to abstain from activities
that could result in pregnancy from screening through 180 days after the last dose of
study treatment, or is of non-childbearing potential. Non-childbearing potential is
defined as follows (by other than medical reasons):
*≥45 years of age and has not had menses for >1 year
- Patients who have been amenorrhoeic for <2 years without history of a
hysterectomy and oophorectomy must have a follicle stimulating hormone value in
the postmenopausal range upon screening evaluation.
- Post-bilateral oophorectomy, or post-tubal ligation. Documented oophorectomy must
be confirmed with medical records of the actual procedure or confirmed by an
ultrasound. Tubal ligation must be confirmed with medical records of the actual
procedure, otherwise the patient must be willing to use 2 adequate barrier
methods throughout the study, starting with the screening visit through 180 days
after the last dose of study treatment. See Section 4.4 for a list of acceptable
birth control methods. Information must be captured appropriately within the
site's source documents.
- Note: Abstinence is acceptable if this is the established and preferred
contraception for the patient.
- Participant must agree to not breastfeed during the study or for 180 days after the
last dose of study treatment.
- Ability to understand and willingness to sign an IRB approved written informed consent
document (or that of legally authorized representative, if applicable).
- Any prior treatment for endometrial cancer or currently receiving chemotherapy for
- Evidence of metastatic disease outside of the cervix or uterus as determined on CT or
- A history of other malignancy ≤ 3 years previous with the exception of basal cell or
squamous cell carcinoma of the skin which were treated with local resection only.
- Previous treatment with an anti-PD-1, anti-PD-L1, or any PD-L2 drug.
- Known brain or leptomeningeal metastases. Patients with known brain metastases must be
excluded from this clinical trial because of their poor prognosis and because they
often develop progressive neurologic dysfunction that would confound the evaluation of
neurologic and other adverse events.
- A history of allergic reactions attributed to compounds of similar chemical or
biologic composition to TSR-042 or other agents used in the study.
- Pregnant and/or breastfeeding. Women of childbearing potential must have a negative
pregnancy test within 7 days of study entry.
- Participant must not be simultaneously enrolled in any interventional clinical trial
- Participant must not have had major surgery ≤ 3 weeks prior to initiating protocol
therapy and participant must have recovered from any surgical effects.
- Participant must not have received investigational therapy ≤ 4 weeks, or within a time
interval less than at least 5 half-lives of the investigational agent, whichever is
shorter, prior initiating protocol therapy.
- Participant has had radiation therapy encompassing >20% of the bone marrow within 2
weeks; or any radiation therapy within 1 week prior to Day 1 of protocol therapy.
- Participant must not have a serious, uncontrolled medical disorder, nonmalignant
systemic disease, or active, uncontrolled infection. Examples include, but are not
limited to, uncontrolled ventricular arrhythmia, recent (within 90 days) myocardial
infarction, chronic obstructive pulmonary disease, uncontrolled major seizure
disorder, unstable spinal cord compression, superior vena cava syndrome, or any
psychiatric disorder that prohibits obtaining informed consent.
- Patient experienced ≥ Grade 3 immune-related AE with prior immunotherapy, with the
exception of non-clinically significant lab abnormalities.
- Participant has a diagnosis of immunodeficiency or has receiving systemic steroid
therapy or any other form of immunosuppressive therapy within 7 days prior to
initiating protocol therapy.
- Participant has a known history of human immunodeficiency virus (type 1 or 2
- Participant has known active hepatitis B (eg, hepatitis B surface antigen [HBsAg]
reactive) or hepatitis C (eg, hepatitis C virus [HCV] ribonucleic acid [qualitative]
- Participant has an active autoimmune disease that has required systemic treatment in
the past 2 years (ie, with use of disease-modifying agents, corticosteroids, or
immunomodulatory 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.
- Participant must not have a history of interstitial lung disease.
- Participant has received a live vaccine within 14 days of initiating protocol therapy.