Tests tulmimetostat alone and with enzalutamide in advanced cancers

Trial details

Who runs it

Novartis Pharmaceuticals

Trial code

NCT04104776EU 2023-508002-20-00

Record updated

19 August 2026

Original description

The purpose of this open-label, first-in-human (FIH) trial is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of DZR123 (Tulmimetostat, CPI-0209), both as monotherapy and in combination with enzalutamide, in patients with advanced solid tumors and lymphomas.Read full original descriptionShow less

A Phase 1/2 Study of DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas

The purpose of this open-label, first-in-human (FIH) trial is to evaluate the safety, tolerability, pharmacokinetics, pharmacodynamics, and preliminary antitumor activity of DZR123 (Tulmimetostat, CPI-0209), both as monotherapy and in combination with enzalutamide, in patients with advanced solid tumors and lymphomas.

Inclusion: All Patients:; Adults aged ≥18 years with life expectancy ≥12 weeks; ECOG performance status 0-1; Adequate recovery from prior therapy-related toxicities (Grade ≤1, with exceptions); Adequate bone marrow, renal, and hepatic function per protocol-defined thresholds; Willingness to provide tumor tissue and blood samples for biomarker analyses; Agreement to protocol-specified contraception requirements; Signed informed consent prior to study procedures; Disease-Specific Inclusion Criteria:; Phase 1 (Dose Escalation):; Histologically or cytologically confirmed locally advanced or metastatic solid tumors or lymphoma; Disease refractory to standard therapy or with no available effective standard treatment; For prostate cancer: castrate testosterone levels maintained throughout the study; Phase 2 (Disease-Specific Cohorts):; M1: ARID1A mutant urothelial carcinoma or other ARID1A mutant solid tumors (with cohort specific prior therapy and RECIST 1.1 measurable disease requirements); M2: ARID1A mutant ovarian clear cell carcinoma after prior platinum-based therapy (and bevacizumab unless contraindicated); M3: ARID1A mutant recurrent/metastatic endometrial carcinoma after platinum therapy and appropriate immunotherapy; M4: Relapsed/refractory peripheral T cell lymphoma or diffuse large B cell lymphoma, transplant-ineligible, with measurable disease; M5: Relapsed/refractory pleural or peritoneal mesothelioma with documented BAP1 loss; M6: Metastatic castration-resistant prostate cancer (mCRPC) with documented progression after AR targeted therapy and taxane chemotherapy; M7: ARID1A wild type endometrial carcinoma (exploratory food-effect cohort); M8: mCRPC treated with DZR123 in combination with enzalutamide, with cohort specific requirements for prior androgen receptor pathway inhibitor and chemotherapy exposure.

Exclusion: Prior solid organ or allogeneic hematopoietic cell transplant; Concurrent malignancy requiring active treatment (with protocol-defined exceptions); Pregnancy, breastfeeding, or inability to comply with protocol requirements; Prior or Concomitant Therapy:; Recent anticancer therapy within protocol-defined washout periods; Prior EZH2 inhibitor treatment; Recent radiation or liver-directed therapies outside allowed windows; Use of strong CYP3A4/5 inhibitors or inducers; Additional Cohort-Specific Exclusions:; M8 (Combination): PSA-only disease, prior investigational androgen receptor pathway inhibitors, significant seizure risk, extensive prior bone marrow irradiation, active inflammatory gastrointestinal disease; Medical Conditions:; Active interstitial lung disease or pneumonitis; Uncontrolled infections or significant gastrointestinal disorders affecting absorption; Active HIV or hepatitis B/C infection; M6 (mCRPC): Bone-only disease, unstable bone lesions, PSA-lowering herbal products, recent prohibited prostate cancer therapies; Clinically significant cardiovascular disease, including uncontrolled arrhythmias or prolonged QTc; All Patients:; Active or untreated symptomatic CNS metastases (with limited exceptions).

ClinicalTrials.gov NCT04104776 · EU CTIS 2023-508002-20-00