A Study of Tulmimetostat DZR123 (CPI-0209) in Patients With Advanced Solid Tumors and Lymphomas

Korábbi kezelés

• 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

Más betegség

• 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

Laborértékek

• Clinically significant cardiovascular disease, including uncontrolled arrhythmias or prolonged QTc

Egyéb

• All Patients:
• Active or untreated symptomatic CNS metastases (with limited exceptions)

• 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