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

About This Trial

This clinical trial is testing an experimental drug called tulmimetostat, given either alone or with a standard medicine called enzalutamide, to see if it is safe and can help shrink or slow tumor growth.
It is open to adults with advanced prostate cancer that has continued to spread or worsen after receiving standard hormone therapies and chemotherapy.
To qualify, your cancer must be visible on imaging scans rather than detected by a rising PSA blood test alone, and you must feel well enough to do most daily activities.
Before joining, you should know that this is an early-stage study that will require extra clinic visits, blood draws, and small tumor tissue samples so doctors can see how your body responds to the treatment.

More Information

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.

Who Can Enroll

Age Range: 18 years and older
Gender: All
Who This Trial is For: This clinical trial is testing an experimental drug called tulmimetostat, given either alone or with a standard medicine called enzalutamide, to see if it is safe and can help shrink or slow tumor growth.

Study Details

Start Date: September 18, 2019
Lead Sponsor: Novartis Pharmaceuticals

Full Eligibility Criteria

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

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