Phase I/Ib study evaluating safety, efficacy, pharmacokinetics and pharmacodynamics of NIZ985 monotherapy and in combination with an anti-PD-1 agent in patients with advanced solid tumors or lymphoma.

BACKGROUND

Heterodimeric IL-15 (NIZ985) shows rapid and indirect effects on different myeloid cells but may upregulate PD-1 (programmed cell death-protein 1) on CD8 + T cells, limiting its therapeutic potential. Combining IL-15 with an anti-PD-1 antibody is known to enhance antitumor immune response and prolong survival in mice.

METHODS

This was a phase I/Ib, open-label, multicenter study (NCT04261439) of NIZ985 single agent (SA) or with an anti-PD-1/CPI agent in patients with advanced solid tumors or lymphoma (responded and progressed on prior anti-PD-1) in a dose escalation (SA/with spartalizumab) and a dose expansion (with tislelizumab) arm. Primary objectives were to assess safety and tolerability including DLTs in cycle 1, adverse events (AEs) and serious AEs, dose interruptions, reductions, and dose intensity of NIZ985 SA and combination therapy. The recommended dose for expansion (RDE) for further investigations was determined.

RESULTS

NIZ985 was safe and well-tolerated, with a safety profile consistent with a previous investigation. Most common AEs with SA were injection site reaction, pyrexia, and transaminase increase. With combination therapy, AEs leading to dose adjustment/interruption were higher with NIZ985 16mg/kg compared to 8mg/kg and 12 mg/kg. NIZ985 exposure after the first dose increased with dose increases and was not affected by concomitant administration of CPIs. The RDE was determined to be 12 µg/kg NIZ985 QW (3 weeks on-1week off).

CONCLUSIONS

While NIZ985 is safe to use in combination with PD-1 inhibitors and showed biological activity, preliminary antitumor efficacy was limited in patients who previously progressed on an anti-PD-1/CPI agent.