lirilumab (BMS-986015)

Actualization of a patient-specific I-O combination treatment selection strategy is feasible, however, determination of de novo integral biomarker thresholds of novel I-O targets to facilitate effective treatment of PD-1-refractory cancer remains fraught. These data emphasize the difficulty of integral biomarker development for I-O in translating from immunotherapy treatment-naïve biospecimens to the selection of patients in the PD-1-refractory state.

P1/2, N=455, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Trial completion date: Aug 2027 --> Feb 2031 | Trial primary completion date: Aug 2027 --> Feb 2031

P1/2, N=316, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Dec 2023 --> Jul 2024

Our data reveal that in the context of NK cells, IFNγ induces the resistance of tumor cells by the upregulation of classical and non-classical MHC-I. Moreover, we reveal insights into NK cell subset reactivity and propose a therapeutic strategy involving combinational monalizumab/lirilumab/DX9 treatment to fully restore the antitumor response across NK cell subsets.

Notably, the epitope includes several key amino acids that vary across the human population, and binding studies demonstrate the importance of these amino acids for lirilumab binding. These studies reveal how KIR variations in patients could influence the clinical efficacy of lirilumab and reveal general concepts for the development of immune checkpoint inhibitors targeting NK cells.

Neoadjuvant nivolumab-based immunotherapy was safe, feasible, and well tolerated in cisplatin-ineligible patients with MIBC. Although ypT0N0 rates were lower than expected, 2-yr survival rates seem to be comparable with those of other neoadjuvant immunotherapy trials. Nivolumab is being evaluated in the CA-017-078 trial (NCT03661320).

P1/2, N=460, Recruiting, Gustave Roussy, Cancer Campus, Grand Paris | Trial completion date: Jan 2022 --> Aug 2027 | Trial primary completion date: Jan 2022 --> Aug 2027

P1/2, N=316, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Nov 2022 --> Dec 2023

Vav1 silencing eliminated disinhibition of NF-κB signaling by lirilumab and avelumab, indicating their disinhibiting effects are Vav1-dependent. This study supports a novel approach to enhancing NK cell lysis against HPV+ cervical cancer cells through combining lirilumab and avelumab.

P1/2, N=316, Active, not recruiting, Bristol-Myers Squibb | Trial completion date: Jan 2022 --> Nov 2022

(Neo)adjuvant N+L was well tolerated with a 43% pathologic response rate. We observed favorable DFS and excellent 2-year OS among high-risk, previously treated patients exhibiting a pathologic response. Further evaluation of this strategy is warranted.

Patients received nivolumab plus ipilimumab (nivo/ipi) or lirilumab (nivo/liri) until complete response (CR), progression, or unacceptable toxicity. While both combinations were active in cHL, the toxicity of nivo/ipi was higher than expected from nivolumab alone. These data suggest no meaningful improvement in the efficacy of the combinations over single-agent nivolumab in the diseases studied.