Pembrolizumab and Radiotherapy for Patients With NK/T Cell Lymphoma

Pembrolizumab and Radiotherapy for Previously Untreated Patients With Limited Stage NK/T Cell Lymphoma Who Are Not Eligible to Chemotherapy

Aim of the trial is to evaluate the activity and tolerability of the anti PD1 agent Pembrolizumab in combination with RadioTherapy for the initial treatment of previously untreated patients with limited stage NK/T cell lymphoma who are not eligible to chemotherapy.

It is planned to enroll 30 patients in chinese sites.

All eligible patients will be treated with standard radiotherapy and concurrent pembrolizumab administered intravenously every 3 weeks. After 6 cycles of pembrolizumab patients with complete remission, partial response and stable disease will continue with pembrolizumab maintenance up to 2 years.

Patients will be followed up to 4 years from treatment start.

This is an interventional, phase II, open label, single arm, multicentric clinical trial to be conducted in China.

The primary objective is to test the efficacy of concurrent RT-Pembrolizumab in patients with limited stage NK/T cell lymphoma and who are not eligible to receive chemotherapy.

The secondary objectives are to further explore the efficacy and safety of a the combination of RT and Pembrolizumab as initial treatment of the patients population.

All eligible patients will be treated with standard IFRT and concurrent pembrolizumab administered intravenously, over 30 minutes starting on day 1 of RT (C1D1, at the dose of 200 mg, every 3 weeks). After 6 cycles of pembrolizumab patients will undergo restaging imaging. Patients with complete remission (CR), partial response (PR) and stable disease (SD) will continue with pembrolizumab maintenance up to 2 years that will be administered intravenously, at the dose of 200 mg, over 30 minutes on day 1 every 3 weeks up to 34 cycles.

The follow-up period will last up to 4 years from treatment start.

Inclusion Criteria:

• Confirmed histological diagnosis of NK/T Cell Lymphoma
• No previous anti-lymphoma treatment
• Age ≥ 18 years
• Ann Arbor stage I-II
• At least one measurable/evaluable site after diagnostic biopsy before treatment start
• At least one of the following high-risk features: age > 60 years, elevated LDH, stage II, primary tumor invasion
• Patient ineligible to receive full dose standard chemotherapy
• ECOG performance status of 0-1
• Signed Informed consent
• Ability to comply with the protocol
• Adequate hematological and organ function;
• Tumor tissue (fresh preferred, archival tissue is also acceptable)
• For women of childbearing potential a negative pregnancy test on day 1 of cycle 1 and agree to adopt an adequate measure to avoid pregnancy during study treatment and for at least one year from end of treatment
• For men agreement to remain abstinent or to use barrier contraception

Exclusion Criteria:

• Advanced stage disease (AA stage III-IV)
• Extranasal type NKTCL
• History of autoimmune disease
• History of other(s) infiltrating cancer(s) in the previous 3 years that were not treated with curative intent or who are still receiving anticancer therapy (including hormone therapy for breast or prostate cancer).
• History of (non-infectious) pneumonitis that required steroids; evidence of interstitial lung disease or active, non-infectious pneumonitis
• Active infection requiring systemic therapy
• Significant cardiovascular disease, myocardial infarction in the previous 3 months, unstable arrhythmias, or unstable angina.
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent
• HBsAg, HCV or HIV positivity. Positive serology is admitted for HBV and HCV but DNA/RNA test must be negative
• Administration of a live attenuated vaccine within 4 weeks before cyle 1 day 1. Patients must not receive live, attenuate vaccines, including influenza vaccines at any time during study.
• Treatment with systemic immunosuppressive medications, including prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide and anti tumor necrosis factor (anti-TNF) agents within 2 weeks prior to cycle 1 day 1; inhaled corticosteroids are allowed.
• Evidence of suspect of CNS disease
• Clinically significant hypersensitivity (e.g., anaphylactic or anaphylactoid reactions to the compound Pembrolizumab itself or to the excipients in its formulation).
• Has had an allogenic tissue/solid organ transplant
• Known history of active TB (Bacillus Tuberculosis)