Checkmate 647: a Phase 2, Open‐label Study of Nivolumab in Relapsed/refractory Primary Central Nervous System Lymphoma or Relapsed/refractory Primary Testicular Lymphoma
Year: 2017
Type: article
Abstract: Introduction: Primary central nervous system lymphoma (PCNSL) and primary testicular lymphoma (PTL) are rare and clinically aggressive forms of large B-cell lymphoma with similar genetic signatures. Prognosis is poor and treatment options are limited for patients (pts) with relapsed/refractory PCNSL or PTL, highlighting a high unmet medical need. Both tumors exhibit frequent 9p24.1 copy number alterations (CNAs) and associated expression of the programmed death-1 (PD-1) ligands, PD-L1 and PD-L2 (Chapuy B, Roemer MG, et al. Blood 2016;127:869–81). Activation of PD-1 signaling via PD-L1/PD-L2 limits T-cell responses, potentially inhibiting antitumor immune surveillance. Nivolumab (nivo) is an immune checkpoint inhibitor that targets PD-1 to restore T-cell activation and antitumor immune responses. Nivo has demonstrated efficacy in relapsed/refractory classical Hodgkin lymphoma, which is characterized by 9p24.1 CNAs and PD-L1 and PD-L2 upregulation (Roemer MG, et al. J Clin Oncol 2016;34:2690–7; Younes A, et al. Lancet Oncol2016;17:1283–94), suggesting that the same mechanism of action may be effective in PCNSL or PTL. In a retrospective study of 5 pts with relapsed/refractory PCNSL or PTL who were treated with nivo, all pts obtained clinical and radiographic responses (4 complete radiographic responses and 1 partial radiographic response in a pt with PCNSL), and 3 pts remain progression free at 13 + –17+ mo (Nayak L, et al. Blood 2017, in press). The current study evaluates the efficacy, safety, and tolerability of nivo in relapsed/refractory PCNSL or PTL. Methods: CheckMate 647 (NCT02857426) is a phase 2, open-label, single-arm, 2-cohort trial assessing single-agent nivo treatment in pts with relapsed/refractory PCNSL or PTL. Adult pts with pathologically confirmed PCNSL or PTL who relapsed or did not respond to ≥1 line of systemic therapy, with Karnofsky Performance Status score ≥ 70, are eligible. Pts with PCNSL must have ≥1 measurable brain lesion; pts with PTL require ≥1 measurable extranodal lesion. Pts should have tumor tissue available for PD-L1 expression testing. Pts with intra-ocular lymphoma without evidence of brain disease, pts with PCNSL who cannot undergo MRI, and those with PCNSL with systemic disease are not eligible. Both cohorts will receive nivo monotherapy. The primary endpoint is objective response rate (ORR), assessed by a blinded independent central review committee. Secondary endpoints include progression-free survival, investigator-assessed ORR and duration of response, and overall survival. All analyses will be performed separately in each cohort. Treatment of 65 pts is planned. Accrual is ongoing. Study support: Bristol-Myers Squibb (BMS). Writing assistance by M Arancillo of Caudex, funded by BMS. Keywords: monoclonal antibodies (MoAb); primary CNS lymphoma (PCNSL); testicular lymphoma.
Source: Hematological Oncology
DOI: 10.1002/hon.2440_2
Institutions: Center for Neuro-Oncology, Dana-Farber Cancer Institute, Columbia University Irving Medical Center, Columbia University, IRCCS Ospedale San Raffaele, Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele, Humanitas University, Hackensack University Medical Center, Memorial Sloan Kettering Cancer Center, Massachusetts General Hospital, University of California San Francisco Medical Center, Mayo Clinic, The Barbara Ann Karmanos Cancer Institute, Hôpital René Huguenin, Institut Curie, UPMC Hillman Cancer Center, University of Pittsburgh Medical Center, Yale Cancer Center, Yale University, University Hospital Heidelberg, Klinikum Stuttgart, City Of Hope National Medical Center, City of Hope, Bristol-Myers Squibb (United States)
Language: English
Subfield: Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funder: Bristol-Myers Squibb
OpenAlex ID: W2621993514