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

Summary

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.

Eligibility

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

Conditions10

Interventions2

Locations22 sites

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