2569 Background: Immune activation is important for survival in cancer. Eftilagimod alfa (E), an antigen-presenting cell (APC) activator, binds to a subset of MHC class II molecules on APCs to mediate lymphocyte, e.g. T cell (CD4/CD8), recruitment/activation. Clinical studies of E in combination with a PD-1 antagonist (P) or chemotherapy (C) have shown promising results in phase 2 studies, and E is currently investigated in a phase 3 study in combination with P and C in first-line NSCLC (NCT06726265). We present cumulative correlation studies of immune activation in blood after administration of E with clinical efficacy in late-stage cancer patients (pts). Methods: Five (5) studies with 569 pts were evaluated. 30 mg E in combination with either P (pembrolizumab IV at 200 mg q3w or 400 mg q6w or 2 mg/kg q3w) or C (paclitaxel 80 mg/m 2 day 1, 8, 15, q4w) was administered SC biweekly for 6 months (mo), then every 2-4 weeks for 6-18 mo in pts with late-stage metastatic NSCLC, HNSCC, melanoma, or breast cancer. Absolute lymphocyte count (ALC) was taken before dosing (day 1 per cycle). ALC response was pre-defined as a change ≥0.2 x 10 9 /L in ≤3 mo on study. Samples for gene expression profile (GEP) were taken pre-dose / 3 mo in a subset (N=111). IFN-g and CXCL10 were assessed pre-dose / after 1 st E admin in a subset (N=79). Clinical efficacy was assessed by iRECIST and survival. Results: Treatment with E led to a rapid (3 mo) and sustained (~12 mo) stat. sign. (p=0.03) ALC gain versus control arm. 54.4% of all pts treated with E were ALC responders (53.6% for E+P; 55.1% for E+C). In ALC responders with E, overall survival (OS) was significantly improved (see Table 1) compared to non ALC responders. Effects were observed irrespective of the combination partner, P or C, with a median increase of 6.8 or 5.2 mo, respectively. In pts treated with P or C alone (control), 40.4% were ALC responders but with no sign. median OS gain. Clinical responders (iPR or iCR as BOR) exhibited consistent upregulation of immune pathways associated with T-cell functions, NK cell functions and cytotoxicity during treatment in GEP analysis. These functions were not upregulated in non-responders. IFN-g and CXCL10 concentrations increased quickly (~8h) and significantly post-first E dosing compared to baseline and levels remained elevated until next E dosing. This effect with E was consistent with P or C. Conclusions: E leads to immediate and sustained ALC increase and TH1 type reaction, which is associated with clinical efficacy in combination with P or C. Treatment Effects Results E (N=408) ALC Responder with E 54.4% (N=222/408) Impact on survival: ALC responder vs. ALC non-responder Median OS+ 7.7 mo(23.4 vs.15.7 mo)HR=0.69; p=0.002 Control arm (N=161) ALC Responder in control arm 40.4% (N= 65/161) Impact on survival: ALC responder vs. ALC non-responder Median OS+2.9 mo(20.4 vs. 17.4 mo)HR=0.98; p=0.93
Forster et al. (Wed,) studied this question.