Efficacy and safety results of a first-in-class PRMT1 inhibitor CTS2190 in patients (pts) with immune checkpoint inhibitor (ICI)–insensitive advanced solid tumors.

e15164 Background: Immuno-cold tumors remain low response rate to ICIs. The treatment options and efficacy are limited for patients after PD-(L)1 inhibitors-based therapy. CTS2190 specifically inhibits arginine methyltransferase 1 (PRMT1) and modulate immune microenvironment by epigenetic gene regulation. Here we present clinical data of CTS2190 (NCT06224387) to demonstrate promising safety and efficacy of CTS2190 in heavily pretreated pts with advanced solid tumors including those ICI-insensitive NSCLC, TNBC and mCRPC. Methods: In Phase I/II study of CTS2190, for dose escalation part, in addition to 60~300 mg regimens (QD, 2 weeks on and 1 week off, 5 days on and 2 days off), the safety and tolerability of 120 mg BID were explored. Results: As of 19 Jan, 2026, 71 pts received CTS2190 treatment (1 at 60 mg, 1 at 120 mg QD, 30 at 180 mg, 29 at 240 mg, 2 at 300 mg, and 6 at 120 mg BID). DLT events of grade (G) 4 platelet count decreased occurred in 1 pt at 240 mg and 2 pts at 300 mg. The most common ≥ G3 TRAE was platelet count decreased (32%). The incidence rates in 180 mg QD and 120 mg BID were 33% and 17%, significant less than that in the 240 mg dose level (41%). Exploratory analysis of median PFS was conducted among various subgroups stratified by clinicopathological features. In 60 response-evaluable pts, there was a trend toward improved median PFS among ICI-insensitive pts compared with ICI-sensitive pts（HR = 0.35, P = 0.001）. A similar trend was observed in the PD-(L)1 primarily resistant NSCLC subgroup（HR = 0.34, P = 0.009).There are no differences in median PFS among subgroups of other features (gender, age, ECOG or prior lines of therapies). In 31 response-evaluable ICI-insensitive pts at active dose, The ORR was 12.9% and disease control rate (DCR) was 68%. Of note, in the subgroup of PD-(L)1 primarily resistant NSCLC pts, the ORR was 19% and the DCR was 75%. 25% ORR was observed in mCRPC pts. In the preliminary overall survival (OS) analysis, the median OS was 663 days for pts with PD-(L)1 primarily resistant NSCLC, for ICI-insensitive all comer pts 663-day cumulative survival rate by Kaplan Meier was 54%.Among 16 pts with available PD-L1 expression data, 9 exhibited PD-L1 expression below 5% and showed more favorable responses compared with those having higher expression. Of these 9 patients, 7 were identified as primarily resistant to PD-(L)1 inhibitors. Conclusions: CTS2190 has shown superior safety and promising efficacy in heavily pretreated pts with advanced solid tumors to achieve the clinical proof-of-concept. More patients are being enrolled at RP2Ds in current phase IIa cohort expansion study in NSCLC, mCRPC, TNBC, PDAC and other indications of interest. Studies to combine CTS2190 with SoCs in solid tumors are being planned. Meanwhile, biomarker exploration on PRMT1, PD-L1 expression, MTAP-null and related DDR genes are ongoing. Clinical trial information: NCT06224387 .