Tulmimetostat administration achieved efficacy in multiple ARID1A mutant bladder, ovarian, and endometrial tumor models and improved cisplatin response in chemotherapy-resistant models. Importantly, a tulmimetostat controlled gene expression signature identified in whole blood from a cohort of 32 cancer patients correlated with tulmimetostat exposure, representing a pharmacodynamic marker for the assessment of target coverage for PRC2-targeted agents in the clinic. Collectively, this data suggests that tulmimetostat has the potential to achieve clinical benefit in solid tumors as a monotherapy but also in combination with chemotherapeutic agents and may be beneficial in various indications with recurrent ARID1A mutations.
P1, N=30, Not yet recruiting, Washington University School of Medicine | Trial completion date: Sep 2029 --> Dec 2029 | Initiation date: Sep 2023 --> Dec 2023 | Trial primary completion date: Oct 2027 --> Jan 2028
1 year ago
Trial completion date • Trial initiation date • Trial primary completion date
24 patients were enrolled (OCCC, n=14; EC, n=10); 50% of each cohort have received ≥3 prior treatment lines. Both cohorts are eligible for Stage 2 expansion, with 1 and 2 confirmed partial responses in patients with OCCC and EC, respectively (Table). The manageable safety profile across all 6 tumor cohorts (n=81) was consistent with known class effects; Grade ≥3 related adverse events (≥10% of patients) included thrombocytopenia, anemia, neutropenia, and diarrhea.
over 1 year ago
Clinical • P2 data
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ARID1A (AT-rich interaction domain 1A) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • STAT3 (Signal Transducer And Activator Of Transcription 3)
Based on response criteria of ORR ≥1/10 pts, the ovarian (M2), endometrial (M3), and mesothelioma (M5) cohorts achieved eligibility for stage 2 expansion (not relevant in M4). The safety profile of tulmimetostat is consistent with EZH2 inhibition and previous data. These preliminary findings in heavily pretreated pts with multiple tumor types, including tumors with ARID1A alterations or BAP1 loss, support ongoing investigation of tulmimetostat.
over 1 year ago
Clinical • P2 data • Metastases
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ARID1A (AT-rich interaction domain 1A) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • BAP1 (BRCA1 Associated Protein 1) • STAT3 (Signal Transducer And Activator Of Transcription 3)
Xenograft-derived organotypic tumor spheroids (xDOTS3) were loaded into 3D devices (AIM Biotech), treated with either CPI-0209, carboplatin, or olaparib alone, or with CPI-0209 for 7 days prior to adding carboplatin or olaparib for an additional 5-11 days. Increased SLFN11 protein level supported the importance of EZH2-SLFN11 axis. Further exploration of CPI-0209 combination in ovarian cancer in known genomic contexts is warranted.