Sarcoma, Clear Cell
Conditions
Keywords
advanced clear cell sarcoma, anti-PDL1
Brief summary
Phase II,single arm study designed to explore the activity of TSR-042, an immunotherapy agent, in patients with a diagnosis of advanced or metastatic clear cell sarcoma (CCS).
Detailed description
Phase II, single arm, not randomized, European multicentric study designed to explore the activity of TSR-042, a human monoclonal anti-PD-1 inhibitor, in a population of patients with a diagnosis of advanced/metastatic clear cell sarcoma (CCS).
Interventions
DRUGTSR-042
TSR-042 is an IgG4 humanized monoclonal antibody that binds with high affinity to PD-1, resulting in inhibition of binding to PD-L1 and PD-L2.
Sponsors
GlaxoSmithKline
Italian Sarcoma Group
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single arm
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Written informed consent 2. Histological centrally confirmed diagnosis of clear cell sarcoma 3. Availability of archived tumor tissue block, or 15 slides. 4. Locally advanced disease 5. Measurable disease based on RECIST 1.1 6. Patient can be naive or previously treated with 1 or 2 systemic regimens given for recurrent and/or metastatic disease 7. Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2 8. Adequate bone marrow function 9. Adequate organ function 10. Cardiac ejection fraction ≥50% 11. At least 18 years of age on day of signing informed consent. 12. Non-pregnant female patients 13. Non-ot breastfeed during the study for 90 days after the last dose of study treatment. 14. Male participant agrees to use an adequate method of contraception 15. No history of arterial and/or venous thromboembolic event within the previous 12 months. 16. Participant receiving corticosteroids may continue as long as their dose is stable for least 4 weeks prior to initiating protocol therapy. 17. Patients who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Exclusion criteria
1. Participant must not be simultaneously enrolled in any interventional clinical trial 2. Previous treatment with any non-investigational agents within 14 days of first day of study drug dosing. 3. 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 4. Other primary malignancy with \<5 years clinically assessed disease-free interval, except basal cell skin cancer, cervical carcinoma in situ, or other neoplasms judged to entail a low risk of relapse 5. Previous treatment with radiation therapy within 14 days of first day of study drug dosing, or patients who have not recovered from adverse events due to agents administered more than 4 weeks earlier 6. Has known active central nervous system (CNS) metastases, leptomeningeal metastases, and/or carcinomatous meningitis. Subjects with previously treated brain metastases may participate provided they are stable, 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 7. Has active, non-infectious pneumonitis 8. Has an active infection requiring systemic therapy 9. Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agents 10. Has received a live vaccine within 30 days of planned start of study therapy 11. Major surgery within 3 weeks prior to study entry 12. Any one of the following currently or in the previous 6 months: Myocardial infarction, congenital long QT syndrome, Torsades de Pointes, arrhythmias right bundle branch block and left anterior hemiblock unstable angina coronary/peripheral artery bypass graft, symptomatic congestive heart failure New York Heart Association Class III or IV, cerebrovascular accident, or transient ischemic attack symptomatic pulmonary embolism. Ongoing cardiac dysrhythmias of Grade \>=3, atrial fibrillation of any grade,or QTcF interval \>470 msec 14. Severe and/or uncontrolled medical disease 15. Patient experienced ≥ Grade 3 immune-related AE with prior immunotherapy 16. 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 17. Any known active hepatitis B or hepatitis C 18. Any known history of human immunodeficiency virus 19. Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) 20. Expected non-compliance to medical regimens 21. Known history of interstitial lung disease 22. Active autoimmune disease that has required systemic treatment in the past 2 years 23. Known severe hypersensitivity reactions to monoclonal antibodies, any history of anaphylaxis, or uncontrolled asthma
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Overall Response Rate | At week 12 | Response rate according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Clinical Benefit Rate | Month 6 | Proportion of patients who experienced Complete Response, Progression Response or Stable Disease for over 6 months |
| Quality of Life according the 30 questions European Organization for Research and Treatment of Cancer Quality of Life Questionnaire | Day1 Cycle 2, Day 1 Cycle 3, Every 3 cycles (Day1Cyle6, Day1Cycle 9, …) and through study completion, an average of 1 year | Evaluation of the quality of life collected with European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30 |
| Quality of Life according the questionnaire Euro Quality Of Life 5 Domains (EQ-5D) | Day1 Cycle 2, Day 1 Cycle 3, Every 3 cycles (Day1Cyle6, Day1Cycle 9, …) and through study completion, an average of 1 year | Evaluation of the quality of life collected with Euro Quality Of Life 5 Domains (EQ-5D) |
| Safety according the Patient Reported Outcome according Common Terminology Criteria for Adverse Events (PRO-CTCAE) | Day1 Cycle 2, Day 1 Cycle 3, Every 3 cycles (Day1Cyle6, Day1Cycle 9, …) and through study completion, an average of 1 year | Evaluation of the quality of safety reported by the patient with the PRO-CTCAE |
| Immune-related RECIST (ir-RECIST) response rate | At weeks 6, 12, 24, 36, 48, 60, 72, 84, 96 | Response rate according ir-RECIST criteria |
| Choi criteria response rate | At weeks 6, 12, 24, 36, 48, 60, 72, 84, 96 | Response rate according Choi criteria |
| Progression Free Survival (PFS) | At 3 and 5 years | Survival without disease progression |
| Overall Survival | At 3 and 5 years | Proportion of patients who are still alive at 36 and 60 months after have started the treatment |
| Adverse events related to the treatment | Week 3, week 6, week 9, week 12, week 18, week 24, week 36, week 48, week 60, week 72 | Safety in term of grading of adverse event is evaluate from the firs treatment dose throughout the study according to CTCAE 5.0 |
| Growth Modulation Index (GMI) | At weeks 6, 12, 24, 36, 48, 60, 72, 84, 96 | Correlation between response and prior disease medical treatment: ratio of time to progression with the nth line of therapy to the those with the n-1th line. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Frequency in the expression of anti-tumor immune cells in PBMC collected at baseline and during TSR-042. | Day1, day15, day45 of treatment and through study completion, an average of 1 year | Immunological monitoring of peripheral blood immune subsets, to evaluate the systemic immunological status of patients, |
| Expression level of PD1 and PDL1 at pre-treatment evaluated on cancer cells and in tumor infiltrating myeloid cells | Day1 (pre-treatment) | Analysis of immune contexture in pretreatment tumor tissue. |
| Frequency in the expression of myeloid-derived suppressor cells in peripheral blood mononuclear cell | Day1, day15, day45 of treatment and through study completion, an average of 1 year | Immunological monitoring of peripheral blood immune subsets, to evaluate the systemic immunological status of patients, |
Countries
Italy
Outcome results
None listed