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Sponsor: Novartis Pharmaceuticals
Conditions: Advanced Solid Tumor, Diffuse Large B Cell Lymphoma, Lymphoma, T-Cell, Mesothelioma, Malignant, Prostatic Neoplasms, Castration-Resistant
Interventions: Tulmimetostat, Enzalutamide
Countries: United States, France, Italy, Poland, South Korea, Spain, United Kingdom
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.
Sex: ALL
Age: 18 Years to —
Healthy volunteers: No
Study type: INTERVENTIONAL
Key Inclusion Criteria: 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 Key Exclusion Criteria: All Patients: Medical Conditions: * Prior solid organ or allogeneic hematopoietic cell transplant * Active or untreated symptomatic CNS metastases (with limited exceptions) * Clinically significant cardiovascular disease, including uncontrolled arrhythmias or prolonged QTc * Active interstitial lung disease or pneumonitis * Uncontrolled infections or significant gastrointestinal disorders affecting absorption * Active HIV or hepatitis B/C infection * 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: * M6 (mCRPC): Bone-only disease, unstable bone lesions, PSA-lowering herbal products, recent prohibited prostate cancer therapies * M8 (Combination): PSA-only disease, prior investigational androgen receptor pathway inhibitors, significant seizure risk, extensive prior bone marrow irradiation, active inflammatory gastrointestinal disease
- Tampa, Florida, United States
- Atlanta, Georgia, United States
- Chicago, Illinois, United States
- Maywood, Illinois, United States
- Baltimore, Maryland, United States
- Boston, Massachusetts, United States
- Boston, Massachusetts, United States
- Ann Arbor, Michigan, United States
- Hackensack, New Jersey, United States
- Buffalo, New York, United States
- New York, New York, United States
- New York, New York, United States
- New York, New York, United States
- Rochester, New York, United States
- The Bronx, New York, United States
- Cincinnati, Ohio, United States
- Philadelphia, Pennsylvania, United States
- San Antonio, Texas, United States
- San Antonio, Texas, United States
- Charlottesville, Virginia, United States
- Seattle, Washington, United States
- Seattle, Washington, United States
- Bordeaux, France
- Bordeaux, France
- Lille, France
- Lyon, France
- Nantes, France
- Nantes, France
- Saint-Herblain, France
- Strasbourg, France
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