Study on TSR-042 in Advanced Clear Cell Sarcoma

NCT04274023 | Terminated Phase 2

• 1 other identifier: ISG-ACCeSs
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

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).

Conditions

Sarcoma, Clear Cell

Keywords

advanced clear cell sarcoma; anti-PDL1

Outcome Measures

Primary Outcomes (1)

• Overall Response Rate

  Response rate according Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  At week 12

Secondary Outcomes (10)

• Immune-related RECIST (ir-RECIST) response rate

  At weeks 6, 12, 24, 36, 48, 60, 72, 84, 96

• Choi criteria response rate

  At weeks 6, 12, 24, 36, 48, 60, 72, 84, 96

• Progression Free Survival (PFS)

  At 3 and 5 years

• Overall Survival

  At 3 and 5 years

• Clinical Benefit Rate

  Month 6

Other Outcomes (3)

• Expression level of PD1 and PDL1 at pre-treatment evaluated on cancer cells and in tumor infiltrating myeloid cells

  Day1 (pre-treatment)

• 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

• 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

Study Arms (1)

TSR-042 arm

EXPERIMENTAL

TSR-042 at a dose of 500 mg in IV infusion (given over t30-minutes) every 21 days for the first 4 doses, followed by 1.000 mg on day 1 of every 42 day.

Drug: TSR-042

Interventions

TSR-042 DRUG

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.

TSR-042 arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent
• Histological centrally confirmed diagnosis of clear cell sarcoma
• Availability of archived tumor tissue block, or 15 slides.
• Locally advanced disease
• Measurable disease based on RECIST 1.1
• Patient can be naive or previously treated with 1 or 2 systemic regimens given for recurrent and/or metastatic disease
• Eastern Cooperative Oncology Group (ECOG) Performance Status ≤ 2
• Adequate bone marrow function
• Adequate organ function
• Cardiac ejection fraction ≥50%
• At least 18 years of age on day of signing informed consent.
• Non-pregnant female patients
• Non-ot breastfeed during the study for 90 days after the last dose of study treatment.
• Male participant agrees to use an adequate method of contraception
• No history of arterial and/or venous thromboembolic event within the previous 12 months.

You may not qualify if:

• Participant must not be simultaneously enrolled in any interventional clinical trial
• Previous treatment with any non-investigational agents within 14 days of first day of study drug dosing.
• 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
• 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
• 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
• 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
• Has active, non-infectious pneumonitis
• Has an active infection requiring systemic therapy
• Has received prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agents
• Has received a live vaccine within 30 days of planned start of study therapy
• Major surgery within 3 weeks prior to study entry
• 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

Sponsors & Collaborators

• Italian Sarcoma Group: lead
• GlaxoSmithKline: collaborator

Study Sites (1)

Fondazione IRCSS Istituto Nazionale dei Tumori

Milan, 20133, Italy

Location

Related Publications (4)

• Granter SR, Weilbaecher KN, Quigley C, Fletcher CD, Fisher DE. Clear cell sarcoma shows immunoreactivity for microphthalmia transcription factor: further evidence for melanocytic differentiation. Mod Pathol. 2001 Jan;14(1):6-9. doi: 10.1038/modpathol.3880249.

  PMID: 11211309 BACKGROUND

• Antonescu CR, Tschernyavsky SJ, Woodruff JM, Jungbluth AA, Brennan MF, Ladanyi M. Molecular diagnosis of clear cell sarcoma: detection of EWS-ATF1 and MITF-M transcripts and histopathological and ultrastructural analysis of 12 cases. J Mol Diagn. 2002 Feb;4(1):44-52. doi: 10.1016/S1525-1578(10)60679-4.

  PMID: 11826187 BACKGROUND

• Stacchiotti S, Grosso F, Negri T, Palassini E, Morosi C, Pilotti S, Gronchi A, Casali PG. Tumor response to sunitinib malate observed in clear-cell sarcoma. Ann Oncol. 2010 May;21(5):1130-1. doi: 10.1093/annonc/mdp611. Epub 2010 Jan 21. No abstract available.

  PMID: 20093352 BACKGROUND

• Tazzari M, Palassini E, Vergani B, Villa A, Rini F, Negri T, Colombo C, Crippa F, Morosi C, Casali PG, Pilotti S, Stacchiotti S, Rivoltini L, Castelli C. Melan-A/MART-1 immunity in a EWS-ATF1 translocated clear cell sarcoma patient treated with sunitinib: a case report. BMC Cancer. 2015 Feb 14;15:58. doi: 10.1186/s12885-015-1044-0.

  PMID: 25880253 BACKGROUND

MeSH Terms

Conditions

Sarcoma, Clear Cell

Interventions

dostarlimab

Condition Hierarchy (Ancestors)

Neoplasms, Connective Tissue; Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma

Study Officials

• Silvia Stacchiotti, MD

  Fondazione IRCCS Istituto Nazionale dei Tumori di Milano

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NETWORK
• Responsible Party: SPONSOR

Model Details: Single arm

Study Record Dates

• First Submitted: February 13, 2020
• First Posted: February 18, 2020
• Study Start: January 29, 2024
• Primary Completion: January 29, 2024
• Study Completion: January 29, 2024
• Last Updated: February 1, 2024

Record last verified: 2024-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1)