A phase Ia, dose-escalation study of IMB071703 injection in patients (pts) with recurrent or metastatic, advanced solid tumors.

e14502 Background: IMB071703(XFab-α4-1BB/CD40L), a 4-1BB Fab and triCD40L fusion protein that activates dendritic cell and primes tumor-reactive T cells, mediates immune response, and further inhibits tumor development. We confirmed the expansion of antigen-specific T cells in various mouse models and potent tumor regression administrated by IMB071703 alone or in combination with gemcitabine in vivo, concomitant with improved tumor-reactive T-cell infiltration. IMB071703 showed no signs of liver toxicity at the dose levels up to 51 mg/kg in a repeated-dose study in non-human primates. Here, we describe initial data from a phase Ia study (CTR20230326). Methods: Eligible patients with recurrent or metastatic, advanced solid tumors were enrolled in this study. IMB071703 was administrated at escalating doses of 0.05, 0.15, 0.5,1.0 and 1.5 mg/kg intratumorally Q1W in Cycle 1 (C1:21days), and Q2W from Cycle 2 and subsequent cycles (Cn+1:28 days). Enrolled pts would first undergo DLT observative assessment (21 days). After pts were assessed safely during DLT observation, they would continue the scheduled dosage of IMB071703 until disease progression, intolerable toxicity or other reasons specified in the clinical protocol. The study objectives included the safety, tolerability, PK, pharmacodynamics, immunogenicity, and preliminary efficacy. Results: 7 pts with recurrent or metastatic, advanced solid tumors (median age 60 years, range 42-71; 4 male, 3 female; prior lines of therapy with range 1-6) were treated. Three dose levels, 0.05 mg/kg(n=1), 0.15 mg/kg(n=3), and 0.5mg/kg(n=3), had been evaluated. 1.0mg/kg dose escalation is ongoing. On cutoff date of 18 Dec. 2023, 1 pt is on the study and 6 pts had discontinued treatment. The reasons for discontinuation included confirmed disease progression (n=5) and other reason(n=1). 7 pts (100%) experienced treatment-emergent adverse events (TEAEs). 5 pts (71%) experienced treatment-related adverse events (TRAEs≥10%): Injection reaction (pain, fever, chill) (28%), fatigue (11%). All TRAEs were ≤grade 2. No DLT was observed. One death due to disease progression, as only a SAE, was identified to be unrelated. No objective response was observed in 6 evaluable pts. 1 pt was SD and 5 pts were PD. Pharmacodynamic data showed CD40 was occupied ≥50% in the 0.5 mg/kg level. The percentage of CTL (CD3+CD8+) in peripheral blood was increased (0.15mg/kg and 0.5mg/kg) Pharmacokinetic analysis also showed the mean half-life of IMB071703 was 2.45 hours in three dose levels. Biomarker analysis indicated 4-1BB up-regulation and PD-1 down-regulation was associated with the favorable response. Conclusions: IMB071703 Showed a good safety profile at the dose levels of 0.05 mg/kg, 0.15 mg/kg, and 0.5mg/kg. Both favorable tolerability and preliminary antitumor activity warrant further evaluation in patients with advanced malignancies. Clinical trial information: CTR20230326 .