| Eligibility |
Inclusion Criteria:
1. Signed informed consent before any study-specific procedure
2. Participant must have an Eastern Cooperative Oncology Group (ECOG) performance status
of = 1
3. Participant must be a female = 18 years of age
4. Life expectancy =3 months
5. Participant must have biopsy-confirmed squamous cell carcinoma, adenocarcinoma, or
adenosquamous carcinoma of the cervix.
6. Patients must have archival tumor tissue available that is formalin-fixed and paraffin
embedded.
7. At diagnosis:
- Federation of Gynecologists and Obstetricians (FIGO) stages IB2, IIA2, IIB with
pelvic lymph node involvement: Biopsy-proven pelvic node involvement, 2 or more
positive nodes by magnetic resonance imaging (MRI) or computed tomography (CT)
(=1.5 cm shortest dimension), 2 or more positive nodes by Positron Emission
Tomography (PET) (with standardized uptake values (SUV) =2.5)
- FIGO stages IIIA, IIIB, IVA
- Any FIGO stage with para-aortic lymph node involvement: Biopsy-proven para-aortic
node involvement, 1 or more positive nodes by MRI or CT (=1.5 cm shortest
dimension), 1 or more positive pelvic nodes by PET (with SUV = 2.5)
8. Subjects must have received combination chemotherapy and radiotherapy (CCRT) with
curative intent. Patients must have received at least 4 doses of weekly cisplatin.
9. Patients must have completed definitive treatment, namely chemo-radiation, up to 12
weeks prior to sign the Informed Consent form.
10. Toxicities resulting from chemo-radiation must resolve to = Grade 1 prior to
randomization.
11. Participant must have adequate organ function, defined as follows:
- Absolute neutrophil count = 1,500/µL
- Platelets = 100,000/µL
- Hemoglobin = 9 g/dL
- Serum creatinine = 1.5× upper limit of normal (ULN) or calculated creatinine
clearance = 50 mL/min using Cockcroft-Gault equation for patients with creatinine
levels > 1.5× institutional ULN
- Total bilirubin = 1.5× ULN OR direct bilirubin = 1× ULN
- Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2.5× ULN
unless liver metastases are present, in which case they must be = 5× 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
12. Participant must agree to not donate blood during the study or for 90 days after the
last dose of study treatment.
13. Negative Test Results for Hepatitis
14. Female participant has a negative serum pregnancy test within 72 hours prior to taking
study treatment if of childbearing potential and agrees to abstain from activities
that could result in pregnancy from screening through 150 days after the last dose of
study treatment, or is of nonchildbearing potential.
15. Participant must agree to not breastfeed during the study or for 150 days after the
last dose of study treatment.
16. Male partners must agree to use an adequate method of contraception starting with the
first dose of study treatment through 150 days after the last dose of study treatment.
17. Participant must be able to understand the study procedures and agree to participate
in the study by providing written informed consent
Exclusion Criteria:
1. Histological types other than in inclusion criteria, like sarcomas, small cell
carcinoma with neuroendocrine differentiation, non-epithelial cancers.
2. FIGO Stage IVB (cancer has spread distantly).
3. Subjects who have undergone a previous hysterectomy defined as removal of the entire
uterus or will have a hysterectomy as part of their initial cervical cancer therapy.
4. Has not achieved at least a partial response by Response Evaluation Criteria in Solid
Tumors (RECIST) v1.1 after completion of CCRT administered with curative intent.
5. Patients previously treated with chemotherapy except when used concurrently with
radiation therapy. Patients who have received either concurrent paclitaxel with
radiation therapy or carboplatin/paclitaxel as adjuvant therapy are ineligible for the
study.
6. Prior treatment with any anti-vascular endothelial growth factor (anti-VEGF) drug,
including bevacizumab, CD137 agonists or immune checkpoint blockade therapies,
anti-PD1, or anti-PDL1 therapeutic antibodies or anti-CTLA 4.
7. Patients with a concomitant malignancy other than non-melanoma skin cancer.
8. History of autoimmune disease
9. History of idiopathic pulmonary fibrosis, organizing pneumonia , drug-induced
pneumonitis, idiopathic pneumonitis, or evidence of active pneumonitis on screening
chest CT scan.
10. History of interstitial lung disease.
11. Active tuberculosis.
12. Signs or symptoms of infection within 2 weeks prior to Cycle 1, Day 1.
13. Administration of a live, attenuated vaccine within 14 days before Cycle 1, Day 1 or
anticipation that such a live attenuated vaccine will be required during the study
Influenza vaccination should be given during influenza season only. Patients must not
receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to
Cycle 1, Day 1 or at any time during the study.
14. Treatment with systemic immunostimulatory agents within 6 weeks or 5 half-lives of the
drug, whichever is shorter, prior to Cycle 1, Day 1.
15. Treatment with systemic immunosuppressive medications within 2 weeks prior to Cycle 1,
Day 1.
16. Women that are breastfeeding or pregnant.
17. Demonstration of any other disease, neurological or metabolic dysfunction, found upon
physical examination or laboratory tests involving a reasonable suspicion of the
existence of a disease or condition that contraindicates the use of an experimental
drug, or that involves an increased risk to the patient of treatment-related
complications.
18. No medical or psychiatric illness that may impede the performance of a systemic or
surgical treatment
19. Participant must not be simultaneously enrolled in any interventional clinical trial
20. Participant must not have had major surgery = 3 weeks prior to initiating protocol
therapy and participant must have recovered from any surgical effects.
21. 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.
22. 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.
23. Participant must not have a known hypersensitivity to TSR-042 components or
excipients.
24. Participant must not have a serious, uncontrolled medical disorder or nonmalignant
systemic disease. 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
25. Participant must not have known, symptomatic brain or leptomeningeal metastases
26. Patient experienced = Grade 3 immune-related adverse events (AE) with prior
immunotherapy, with the exception of non-clinically significant lab abnormalities.
27. Participant has a known history of human immunodeficiency virus (type 1 or 2
antibodies).
|
