Abstract P124

Activity of Nivolumab with Decitabine Cedauzurine (DEC-C) in Relapsed/Refractory Hodgkin Lymphoma (cHL): Results from an ETCTN Phase 1 Study

Patients with classic Hodgkin lymphoma (cHL) who relapse after checkpoint inhibitor (CPI) have limited treatment options; effective therapies remain an unmet need. Epigenetic silencing leading to exhausted T-cells is a mechanism of CPI resistance.

We tested the combination of oral decitabine and cedazuridine (DEC-C) a fixed-dose formulation of the hypomethylating agent decitabine, in combination with the checkpoint inhibitor (CPI) Nivolumab (Nivo) in a Phase 1 multicenter NCI/CTEP study of patients with R/R cHL and DLBCL. We present the cHL cohort here. A total of 15 patients were treated between 07/23 and 3/26.

DEC-C was given at a dose of 35mg/100mg daily x 5 (DL 1) or x 3 (DL-1) with standard dose Nivo. Two patients were treated in DL 1 and 13 patients in DL-1. Patients were heavily pre-treated with a median of 4 prior lines of therapy (range 2 to 16); 10 patients had prior hematopoietic stem cell transplant (HCT): 7 auto, 3 allo. 12 patients received prior CPI; all CPI treated patients relapsed after CPI, and 10 were considered refractory. 15 patients are evaluable for safety.

All patients had adverse events (AEs) across all grades which were low grade and included anemia, thrombocytopenia, nausea, headache, dyspnea, fatigue, and transaminase elevation. Gr 3 and 4 AEs considered at least possibly related were primarily hematologic and included neutropenia (7), anemia (2), thrombocytopenia (2), leukopenia (5), lymphocytopenia (2), and neutropenic fever (2); Gr 3 and 4 non-hematologic AEs included: dyspnea (2), hypokalemia (2), hyperkalemia (1), and cardiomyopathy (1). 12 of 15 patients are currently evaluable for response, of the 3 who are not evaluable, one died within a month of starting therapy due to disease, one came off treatment due to AEs, and one is too early for assessment. The overall response rate was 8/12 (66.7%) with 1 CR and 7 PR; an additional 4 (33.33%) patients had stable disease for a clinical benefit rate of 100%.

The 12- month PFS is 64% with a median PFS of 511 days, 95% CI (0.347, 0.835). The median OS is not reached, with one year OS of 79%, 95% CI (0.479, 0.927). DEC-C in combination with Nivo had manageable toxicity with durable clinical benefit in heavily pretreated predominantly HCT and CPI refractory cHL patients, for whom PFS is generally short. Future platforms could build on this strategy to maximize efficacy for these patients with limited treatment options.