STING agonist JMKX000197 infusion in patients with malignant pleural effusion: Preliminary results from a prospective phase Ib study.

2598 Background: Indwelling pleural catheter (IPC) is frequently used for symptomatic malignant pleural effusion (MPE), its therapeutic benefits remain limited. JMKX000197 is a novel small molecule stimulator of interferon genes (STING) agonist that activates STING to induce type I interferons and pro-inflammatory cytokines and may have a promising clinical prospect for the treatment of MPE. Methods: Eligible patients had advanced solid tumors with moderate-to-large MPE and had progressed on systemic therapy or had poorly controlled effusion. Patients were randomized assigned in a 1:1:1 ratio to receive intrapleural infusions of JMKX000197 (150 μg or 300 μg) combined with IPC or IPC alone (control) on day 1 and day 8. Here, we report safety, tolerability, preliminary efficacy, and PK/PD characteristics from the phase Ib study of JMKX000197 (NCT06740019). Results: As of October 15, 2025, 35 patients were enrolled (45.7% female, median age 59 years, 71.4% with lung adenocarcinoma). 2 patients withdrew from the study without receiving any treatment after randomization, thus, the safety and efficacy analysis was based on 33 patients who received treatment. Among 33 patients, 1 patient in the 300 μg group withdrew the informed consent after one dose while 32 patients (97%) completed the two-dose regimen (11 in 150 μg group N=11, 9 in 300 μg group N=10, and 12 in control group N=12). Treatment-emergent adverse events (TEAEs) occurred in 100%, 90%, and 83.3% of patients in the 150 μg, 300 μg, and control groups, respectively. Grade ≥3 TEAEs occurred in 3(27.3%), 1 (10%) and 1 (8.3%) patients in each group. 2 patients in 150 μg group and 5 patients in 300 μg group experienced grade 1–2 cytokine release syndrome (CRS), which were adverse event of special interest, all resolved with supportive care. No TEAE led to treatment discontinuation or death. Puncture-free survival (PuFS) was defined as the period from the removal of the IPC immediately after the last dose of treatment to the next therapeutic puncture and/or drainage or death, whichever occurs first. The median PuFS was 37 days, 116 days, and 56 days in the 150 μg, 300 μg, and control groups, respectively. Limited exposure of JMKX000197 in plasma was observed (>700 fold lower than that in pleural effusion). PD analysis showed significant elevation of IFN-β in both plasma and pleural effusion (higher in pleural effusion), along with increased TNF-α, IP-10, MCP-1, and IL-6. Immunophenotyping demonstrated enhanced CD8+ T-cell activation and reduced Treg cell proportions post-treatment (both in peripheral blood and pleural effusion). Conclusions: Intrapleural JMKX000197 exhibited a manageable safety profile and promising preliminary efficacy in MPE patients, with a better efficacy at the 300 μg dose. JMKX000197 may induce the production of pro-inflammatory cytokines and subsequently activate the tumor microenvironment. Clinical trial information: NCT06740019 .