^
    9d
    TulmiSTAR-02: A Phase I/II Open-label Study of Tulmimetostat in Combination With Darolutamide vs. Darolutamide, and Tulmimetostat With Abiraterone in Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC) (clinicaltrials.gov)
    P1/2, N=203, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting
    Enrollment open
    |
    abiraterone acetate • Nubeqa (darolutamide) • tulmimetostat (DZR123)
    2ms
    An Open-label Dose Escalation and Expansion, Followed by a Phase II Study of Tulmimetostat (DZR123) and JSB462 (Luxdegalutamide) in Patients With Progressive Metastatic Castrate Resistant Prostate Cancer (mCRPC) (TulmiSTAR-01) (clinicaltrials.gov)
    P1/2, N=188, Recruiting, Novartis Pharmaceuticals | Not yet recruiting --> Recruiting
    Enrollment open
    |
    tulmimetostat (DZR123) • luxdegalutamide (ARV-766)
    2ms
    An Open-label Dose Escalation and Expansion, Followed by a Phase II Study of Tulmimetostat (DZR123) and JSB462 (Luxdegalutamide) in Patients With Progressive Metastatic Castrate Resistant Prostate Cancer (mCRPC) (TulmiSTAR-01) (clinicaltrials.gov)
    P1/2, N=188, Not yet recruiting, Novartis Pharmaceuticals
    New P1/2 trial
    |
    tulmimetostat (DZR123) • luxdegalutamide (ARV-766)
    2ms
    TulmiSTAR-02: A Phase I/II Open-label Study of Tulmimetostat in Combination With Darolutamide vs. Darolutamide, and Tulmimetostat With Abiraterone in Patients With Metastatic Hormone-sensitive Prostate Cancer (mHSPC) (clinicaltrials.gov)
    P1/2, N=203, Not yet recruiting, Novartis Pharmaceuticals
    New P1/2 trial
    |
    abiraterone acetate • Nubeqa (darolutamide) • tulmimetostat (DZR123)
    6ms
    CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer (clinicaltrials.gov)
    P1, N=30, Recruiting, Lan Coffman | Trial primary completion date: Jul 2026 --> Nov 2026
    Trial primary completion date • Platinum sensitive
    |
    BRCA (Breast cancer early onset)
    |
    BRCA mutation
    |
    carboplatin • tulmimetostat (DZR123)
    7ms
    FIH: A Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas (clinicaltrials.gov)
    P1/2, N=275, Recruiting, Novartis Pharmaceuticals | N=210 --> 275 | Trial completion date: Mar 2026 --> Feb 2030 | Trial primary completion date: Dec 2025 --> Feb 2030
    Enrollment change • Trial completion date • Trial primary completion date
    |
    MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • BAP1 (BRCA1 Associated Protein 1)
    |
    MSI-H/dMMR • ARID1A mutation
    |
    Xtandi (enzalutamide) • tulmimetostat (DZR123)
    8ms
    CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer (clinicaltrials.gov)
    P1, N=30, Recruiting, Lan Coffman | Trial completion date: Aug 2028 --> Dec 2028 | Trial primary completion date: May 2025 --> Jul 2026
    Trial completion date • Trial primary completion date • Platinum sensitive
    |
    BRCA (Breast cancer early onset)
    |
    BRCA mutation
    |
    carboplatin • tulmimetostat (DZR123)
    9ms
    Polycomb repressive complex 2 (PRC2) pathway's role in cancer cell plasticity and drug resistance. (PubMed, Funct Integr Genomics)
    Inhibitors like MAK683 and EED226 disrupt EED's ability to maintain PRC2 activity, thereby reducing H3K27me3 levels and reactivating tumor suppressor genes. Valemetostat, a dual inhibitor of both EZH2 and EED, has shown promising results in aggressive cancers like diffuse large B-cell lymphoma and small-cell lung cancer, underlining the therapeutic potential of targeting multiple PRC2 components...Tazemetostat, a selective EZH2 inhibitor, has demonstrated significant clinical efficacy in EZH2-mutant cancers, such as non-Hodgkin lymphomas and epithelioid sarcoma. However, the compensatory function of enhancer of zeste homolog 1 (EZH1) in some cancers requires dual inhibition strategies, as seen with agents like UNC1999 and Tulmimetostat, which target both EZH1 and EZH2. Given PRC2's multifaceted role in cancer biology, its inhibition represents a promising avenue for therapeutic intervention. The continued development of PRC2 inhibitors and exploration of their use in combination with standard chemotherapy or immunotherapy has great potential for improving patient outcomes in cancers driven by PRC2 dysregulation.
    Review • Journal • IO biomarker
    |
    EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit)
    |
    EZH2 mutation
    |
    Tazverik (tazemetostat) • Ezharmia (valemetostat) • tulmimetostat (DZR123) • UNC1999 • MAK683
    10ms
    CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer (clinicaltrials.gov)
    P1, N=30, Recruiting, Lan Coffman | Trial completion date: Aug 2029 --> Aug 2028 | Trial primary completion date: Jan 2027 --> May 2025
    Trial completion date • Trial primary completion date
    |
    BRCA (Breast cancer early onset)
    |
    BRCA mutation
    |
    carboplatin • tulmimetostat (DZR123)
    over1year
    Comprehensive Target Engagement by the EZH2 Inhibitor Tulmimetostat Allows for Targeting of ARID1A Mutant Cancers. (PubMed, Cancer Res)
    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.
    Journal
    |
    ARID1A (AT-rich interaction domain 1A) • BCL11B (BAF Chromatin Remodeling Complex Subunit BCL11B)
    |
    cisplatin • tulmimetostat (DZR123)
    almost2years
    CPI-0209 Plus Carboplatin in Patients With Platinum Sensitive Recurrent Ovarian Cancer (clinicaltrials.gov)
    P1, N=30, Recruiting, Lan Coffman | Not yet recruiting --> Recruiting | Trial primary completion date: Dec 2027 --> Jan 2027
    Enrollment open • Trial primary completion date • Combination therapy
    |
    BRCA (Breast cancer early onset)
    |
    BRCA mutation
    |
    carboplatin • tulmimetostat (DZR123)
    almost2years
    Tulmimetostat (CPI-0209) in Patients With Mycosis Fungoides and Sézary Syndrome (clinicaltrials.gov)
    P1, N=30, Recruiting, Washington University School of Medicine | Not yet recruiting --> Recruiting
    Enrollment open
    |
    tulmimetostat (DZR123)