Study of MK-3475 Alone or in Combination With Copanlisib in Relapsed or Refractory NK and T-cell Non-Hodgkin Lymphoma

Summary

This is a multicenter, single-arm, open label, study consisting of two cohorts. Cohort 2 explores the combination of copanlisib and pembrolizumab in patients with relapsed or refractory NKTCL, who have received at least 1 prior systemic therapy. Cohort 2 will include a phase 1 portion (cohort 2a) to determine the recommended phase 2 dose (RP2D) utilizing a standard 3+3 design, followed by a phase II portion where patients will be treated at the RP2D (cohort 2b). The primary endpoint for cohort 1 was progression-free survival; the primary endpoint for cohort 2a will be to determine RP2D for the combination therapy; and overall response rate at the end of 4 treatment cycles for cohort 2b. Patients will be assessed for response with PET CT or CT every 12 weeks using the revised Cheson criteria. Correlative endpoints will be exploratory and assess PD-1 expression on peripheral blood lymphocytes; peripheral blood T-cell and NK-cell functional assays; PD-1 and PD-L1 expression on tumor tissue; tumor infiltrating lymphocytes and gene expression panels using the nanostring technology as prognostic and predictive biomarkers, as well as monitoring of minimal residual disease via high-throughput sequencing of cell free tumor DNA, and exosome analysis.

Timeline

Start

2016-01-05

Primary completion

2020-02-25

Completion

2020-02-25

Publications

• Results Barta SK, Zain J, MacFarlane AW 4th, Smith SM, Ruan J, Fung HC, Tan CR, Yang Y, Alpaugh RK, Dulaimi E, Ross EA, Campbell KS, Khan N, Siddharta R, Fowler NH, Fisher RI, Oki Y. Phase II Study of the PD-1 Inhibitor Pembrolizumab for the Treatment of Relapsed or Refractory Mature T-cell Lymphoma. Clin Lymphoma Myeloma Leuk. 2019 Jun;19(6):356-364.e3. doi: 10.1016/j.clml.2019.03.022. Epub 2019 Apr 3.

Drugs

Indications