Abstract P112

Preliminary Results of Nivolumab and Axatilimab in Patients with Relapsed/​Refractory Classical Hodgkin Lymphoma refractory to anti-PD-1 therapy

Background: Patients (pts) with relapsed/refractory (r/r) classical Hodgkin lymphoma (cHL) progressing on anti-PD-1 therapy have poor outcomes. Tumor Associated Macrophages (TAMs) expressing colony stimulating factor 1 receptor (CSF1-R) have been implicated in resistance to anti-PD-1 therapy through (i) direct inhibition of cytotoxic T lymphocytes (CTLs) and (ii) phagocytosis of the anti-PD-1 antibody. Pre-clinical studies suggest that combination of anti-PD-1 and anti-CSF1-R blockade can result in upregulation of CTLs and increased PD-L1 expression.

Methods: We designed a phase 2 dose de-escalation trial of nivolumab and axatilimab (anti-CSF1-R monoclonal antibody) in pts with r/r cHL who have sub-optimal response to anti-PD-1-based therapy to determine the safety and efficacy of the combination (NCT05723055). Pts received axatilimab 3 mg/kg (with DL-1 dose of 2mg/kg) and nivolumab 480 mg Q4 weeks until progression or toxicity.

Results: Six pts have been enrolled with a median age of 46 years (range, 27-78). The median lines of prior therapy were 4 (range, 2-8) and 50% had prior autologous stem cell transplant. Five pts had progressive disease and 1 pt had partial response (PR) on anti-PD-1 based therapy as the last line of treatment. No dose limiting toxicities were observed. Three pts had G 1-2 periorbital edema. There were 4 treatment-related G3 adverse events (AEs) including: asymptomatic CPK elevation (2), hypotension (1), and meningitis (1). Immune-related AEs were G 1-2 rash (2), G1 pneumonitis (1), and G3 meningitis (1). The pt with G3 meningitis was in complete response (CR) after 17 cycles of treatment and discontinued further treatment after developing meningitis.

Of the 5 pts evaluable for response, the best ORR was 80% (40% CR and 40% PR) (Fig 1, top panel). Median time to response was 2.2 months (mo). Median duration of response was 16 mo (95% CI 1.8 mo – NA) and median duration of response in complete responders was 17.3 mo. With a median follow up of 5.75 mo, median PFS was 5.5 mo (95% CI 3.5 mo– NA) with 1-year PFS of 40% (95% CI 14% - 99%). In the correlative blood analysis, we observed an increase in dendritic cells and a decrease in neutrophils in responders (Fig 1, bottom panel).

Conclusions: The combination demonstrated a manageable safety profile and encouraging preliminary antitumor activity, including durable CR in a subset of pts. Anti-CSF1-R treatment can restore or enhance the effectiveness of immune checkpoint blockade.