Abstract P130

Response and Survival Results from a Phase II Trial of Pembrolizumab and Entinostat in Relapsed/Refractory Hodgkin Lymphoma

Introduction: Targeting PD-1 is a highly effective strategy in HL and is rapidly being incorporated into upfront regimens. Strategies for relapsed or refractory (R/R) disease remains an unmet need, especially in those with prior anti-PD1 exposure. We tested whether histone deacetylase (HDAC) inhibition could restore anti-PD-1 sensitivity.

Methods: Patients with R/R HL after ≥ 2 systemic therapies were eligible. Prior therapy with an HDAC inhibitor and/or anti-PD1 therapy was allowed. Treatment was pembrolizumab 200 mg every 21 days plus entinostat 5-7 mg on days 1, 8 and 15 of each 21-day cycle. Treatment was continued until progression, unacceptable toxicity, or death, for a max of 35 cycles. If one of the study drugs was discontinued, the other could be continued. The primary endpoint was 12-month progression-free survival (PFS). PFS was measured from treatment initiation to progression or death, with censoring if patients completed treatment (without progression), received transplant or radiation, or stopped treatment due to an adverse event or clinical decision. The null hypothesis was a 12-month PFS of 40% versus a 12-month PFS of 60%.

Results: Thirty-nine patients enrolled. The median number of prior therapies was 5 (range: 2-18). Prior therapies included brentuximab vedotin (82%), anti-PD1 (74%), HDAC inhibitor (10%), and/or autoHCT (67%). Twenty-two patients (56%) had prior progression of disease (POD) to anti-PD1, including 16 (41%) with POD to anti-PD1 as the last line of therapy prior to enrollment.

Of 38 evaluable patients, the complete response rate (CRR)/ORR was 47% and 63%, respectively. Stratifying patients by prior exposure and response to anti-PD1, CRR/ORR was as follows: (1) prior anti-PD1 at any timepoint: 36% (10/28)/ 50% (14/28); (2) anti-PD1 naïve: 80% (8/10)/100% (10/10); (3) anti-PD1 sensitive: 40% (2/5)/40% (2/5); (4) prior POD to anti-PD1: 36% (8/22)/55% (12/22), (5) POD to anti-PD1 as last line of therapy: 31% (5/16)/44% (7/16). The 12-month PFS was 81% (95% CI 69-96) (Figure). The median PFS was not reached. The median duration of response was 24 months (95% CI 10-NR).

Adverse events (AE) of ≥ grade 3 occurred in 30 (77%) patients. The most common AEs of ≥ grade 3 were neutropenia (n=17, 44%) and thrombocytopenia (n=11, 28%).

Conclusions: Pembrolizumab and entinostat showed high response rates and encouraging PFS in R/R HL, including in patients with prior anti-PD1 antibody exposure.

Authors

Robert Stuver, Santosha Vardhana, Nivetha Ganesan, Neena Mahajan, Alexander Boardman, Philip Caron, Kevin David, Zachary Epstein-Peterson, Lorenzo Falchi, Paola Ghione, Paul Hamlin, Francisco Hernandez-Ilizaliturri, Steven Horwitz, Andrew Intlekofer, William Johnson, Reem Karmali, Anita Kumar, Jennifer Lue, Efrat Luttwak, Ariela Noy, Colette Owens, Maria Palomba, Gilles Salles, Heiko Schoder, David Sermer, Raphael E. Steiner, Pallawi Torka, Andrew Zelenetz, Gottfried von Keudell, Alison Moskowitz