Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as Tulmimetostat DL1 QD, Tulmimetostat DL1, Tulmimetostat Doses 1 or 2 QD, Tulmimetostat Doses 1 or 2, Tulmimetostat RP2D QD, Tulmimetostat RP2D, CPI-0209, DZR123
Tulmimetostat · 5 trials · 14 indications
MTD will be determined via Dose-limiting toxicity (DLT)s defined as any grade 3-4 non-hematological or grade 4 hematological toxicity at least possibly related to the treatment, occurring during the first two cycles of treatment and per Cancer Therapy Evaluation Program (CTEP) Common Terminology Criteria for Adverse Events (CTCAE) version 5.
A dose-limiting toxicity was defined as an adverse event or abnormal laboratory value that was not clearly attributable to the underlying disease or an extraneous cause, occurred during the first 28 days of treatment with tulmimetostat, and met the protocol-defined dose-limiting toxicity criteria. Adverse events were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0. Dose-limiting toxicities were included in the Bayesian Logistic Regression Model used to support dose-escalation decisions.
The incidence, type, frequency, seriousness, and severity of adverse events and serious adverse events will be summarized. Severity will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 5.0.
The number of participants with dose reductions, dose interruptions, or permanent discontinuations, including the reasons for the dose adjustments, will be summarized by treatment group and dose cohort.
Dose intensity, calculated as the actual cumulative dose received divided by the actual duration of exposure, and relative dose intensity, calculated as the dose intensity divided by the planned dose intensity, will be summarized using descriptive statistics for each study drug.
The duration of exposure, in months, to each study drug will be summarized using descriptive statistics by treatment group and dose cohort.
Prostate-Specific Antigen (PSA) response rate is defined as the proportion of participants who achieved a prostate-specific antigen level below 0.2 ng/mL at Month 6, confirmed by a second prostate-specific antigen assessment performed at least 3 weeks later.
A dose-limiting toxicity (DLT) is defined as an adverse event or abnormal laboratory value assessed as unrelated to disease, disease progression, inter-current illness/injury, or concomitant medications that occurs within the first 28 days of treatment with tulmimetostat and JSB462 and meets any of the criteria specified in the protocol. The National Cancer Institute Common Terminology Criteria for Adverse events (NCI CTCAE) version 5.0 will be used for all grading. For the purpose of dose-escalation decisions, DLTs will be considered and included in the Bayesian Logistic Regression Model (BLRM).
The analysis of adverse events will include categorization by type, frequency, and severity, as graded by the NCI CTCAE version 5.0.
The number of participants with dose adjustments (reductions, interruption, or permanent discontinuation) will be summarized by treatment arm.
Dose intensity (computed as the ratio of actual cumulative dose received and actual duration of exposure) and the relative dose intensity (computed as the ratio of dose intensity and planned dose intensity) will be summarized by means of descriptive statistics
The duration of exposure (in months) to Tulmimetostat and JSB462 (Part 1a and Part 1b) will be summarized by means of descriptive statistics
PSA50 is defined as a PSA reduction of at least 50% from baseline at 6 months confirmed by a second PSA measurement ≥ 3 weeks later.
The maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of Tulmimetostat as monotherapy in patients with advanced tumors.
ORR is defined as the proportion of patients with a best overall response of complete response (CR) or partial response (PR) based on RECIST 1.1 or applicable response criteria
The maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) of Tulmimetostat in combination with enzalutamide in patients with castration-resistant prostate cancer (mCRPC) with measurable soft tissue disease.
Prostate-Specific Antigen 50 (PSA50) is defined as a ≥ 50% decrease in PSA levels from baseline at any timepoint, confirmed by a second PSA measurement ≥ 3 weeks without any PSA progression in between
| Arm | Type | Description |
|---|---|---|
| CPI-0209 (100 mg) + carboplatin | EXPERIMENTAL | CPI-0209: 100 mg (oral dosing) carboplatin administered intravenously as per institutional standards |
| CPI-0209 (150 mg) + carboplatin | EXPERIMENTAL | CPI-0209: 100 mg (oral dosing) carboplatin administered intravenously as per institutional standards |
| Phase I: Group A (part 1) | EXPERIMENTAL | Tulmimetostat administered orally once daily (QD) at escalating dose levels in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT) throughout the study. |
| Phase I: Group B (part 2) | EXPERIMENTAL | Tulmimetostat administered orally once daily (QD) at escalating dose levels in combination with abiraterone 1000 mg orally once daily (QD). Participants will continue androgen deprivation therapy (ADT). Abiraterone will be administered with prednisone/prednisolone according to local prescribing information. |
| Phase II: Arm 1 | EXPERIMENTAL | Tulmimetostat Dose 1 orally once daily (QD) in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT). |
| Phase II: Arm 2 (Optional) | EXPERIMENTAL | Tulmimetostat Dose 2 orally once daily (QD) in combination with darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT). This arm will be included if two recommended dose(s) for expansion are selected from Phase I. |
| Phase II: Arm 3 (Control) | ACTIVE_COMPARATOR | Darolutamide 600 mg orally twice daily (BID). Participants will continue androgen deprivation therapy (ADT). |
| Part 1a: Cohort DL1A | EXPERIMENTAL | Tulmimetostat DL1 QD + JSB462 Dose 1 QD |
| Part 1a: Cohort DL1B | EXPERIMENTAL | Tulmimetostat DL1 QD + JSB462 Dose 2 QD |
| Part 1a: Cohort DL2A | EXPERIMENTAL | Tulmimetostat DL2 QD + JSB462 Dose 1 QD |
| Part 1a: Cohort DL2B | EXPERIMENTAL | Tulmimetostat DL2 QD + JSB462 Dose 2 QD |
| Part 1a: Cohort DL3A | EXPERIMENTAL | Tulmimetostat DL3 QD + JSB462 Dose 1 QD |
| Part 1a: Cohort DL3B | EXPERIMENTAL | Tulmimetostat DL3 QD + JSB462 Dose 2 QD |
| Part 1b : Arm A | EXPERIMENTAL | Tulmimetostat Dose 1 QD + JSB462 QD |
| Part 1b: Arm B | EXPERIMENTAL | Tulmimetostat Dose 2 QD + JSB462 QD |
| Part 2: Arm 1 | EXPERIMENTAL | Tulmimetostat RP2D QD + JSB462 QD |
| Part 2: Arm 2 | ACTIVE_COMPARATOR | Standard of Care at the discretion of the investigator |
| Dose De-Escalation Cohort: Tulmimetostat (DZR123) | EXPERIMENTAL | Daily DZR123 by mouth for days 1-28 of each 28-day cycle. Dose will depend on dose level assignment of 300 mg daily, 250 mg daily, or 200 mg daily. |
| Dose Expansion Cohort: Tulmimetostat (DZR123) - 300 mg | EXPERIMENTAL | Daily DZR123by mouth for days 1-28 of each 28-day cycle. Dose will be the maximum-tolerated dose found during the dose de-escalation cohort which was 300 mg. |
| Dose Expansion Cohort: Tulmimetostat (DZR123) - 200 mg | EXPERIMENTAL | Daily DZR123 by mouth for days 1-28 of each 28-day cycle. Dose will be 200 mg as the maximum tolerated dose of 300 mg found during the initial dose expansion cohort caused numerous dose reductions. |
| Phase 1 | EXPERIMENTAL | Eligible participants with advanced tumors will receive escalating doses of Tulmimetostat once per day orally. |
| Phase 2 - Cohort M1 (Advanced/metastatic solid tumors or urothelial carcinoma with ARID1A mutation) | EXPERIMENTAL | Eligible participants with advanced/metastatic solid tumors (excluding ovarian clear cell and endometrial carcinoma) or urothelial carcinoma, confirmed to have ARID1A mutations will receive oral Tulmimetostat once daily in 28-day treatment cycles. |
| Phase 2 - Cohort M2 (Ovarian clear cell carcinoma with ARID1A mutation) | EXPERIMENTAL | Eligible participants with advanced ovarian clear cell carcinoma, confirmed to have ARID1A mutations, who have received prior platinum-based chemotherapy will receive oral Tulmimetostat once daily in 28-day treatment cycles. |
| Phase 2 - Cohort M3 (Endometrial carcinoma with ARID1A mutation) | EXPERIMENTAL | Eligible participants with recurrent, metastatic, or unresectable endometrial carcinoma, confirmed to have ARID1A mutations, and prior platinum-based therapy will receive oral Tulmimetostat once daily in 28-day treatment cycles. |
| Phase 2 - Cohort M4 (Relapsed/refractory lymphoma (PTCL or DLBCL)) | EXPERIMENTAL | Eligible participants with relapsed or refractory peripheral T-cell lymphoma (PTCL) or diffuse large B-cell lymphoma (DLBCL), including those with EZH2 hotspot mutations will receive oral Tulmimetostat once daily in 28-day treatment cycles. |
| Phase 2 - Cohort M5 (Malignant mesothelioma with BAP1 loss) | EXPERIMENTAL | Eligible participants with relapsed or refractory malignant pleural or peritoneal mesothelioma, confirmed to have BAP1 loss will receive oral Tulmimetostat once daily in 28-day treatment cycles. |
| Phase 2 - Cohort M6 (Metastatic castration-resistant prostate cancer (mCRPC)) | EXPERIMENTAL | Eligible participants with mCRPC, measurable soft tissue disease, and prior treatment with at least one androgen receptor signaling inhibitor and one taxane-based chemotherapy will receive oral Tulmimetostat once daily in 28-day treatment cycles. |
| Phase 2 - Cohort M7 (Food effect in ARID1A wildtype endometrial carcinoma) | EXPERIMENTAL | Eligible participants with recurrent, advanced endometrial carcinoma that is ARID1A wildtype (no ARID1A mutation), to evaluate the effect of food on DZR123 pharmacokinetics will receive oral Tulmimetostat once daily in 28-day treatment cycles. |
| Cohort M8 - Part 1 (Tulmimetostat + enzalutamide in mCRPC) | EXPERIMENTAL | Eligible participants with mCRPC receive DZR123 in combination with enzalutamide. Part 1 is dose escalation to determine the recommended dose. |
| Cohort M8 - Part 2 (Tulmimetostat + enzalutamide in mCRPC) | EXPERIMENTAL | Eligible participants with mCRPC receive DZR123 in combination with enzalutamide. Part 2 is expansion at the selected dose to further assess safety and antitumor activity. |
| Name | Type | Description |
|---|---|---|
| CPI-0209 | DRUG | A second-generation EZH2 inhibitor that has been designed to achieve comprehensive anti-cancer target coverage through extended on-target residence time. |
| carboplatin | DRUG | Carboplatin is a chemotherapy drug that contains the metal platinum. It stops or slows the growth of cancer cells and other rapidly growing cells by damaging their DNA. |
| Tulmimetostat | DRUG | Tulmimetostat is an oral dual EZH1/EZH2 inhibitor administered once daily. In Phase I, escalating dose levels will be evaluated in combination with darolutamide or abiraterone. In Phase II, one or two dose levels selected from Phase I will be evaluated in combination with darolutamide. |
| Darolutamide | DRUG | Darolutamide 600 mg administered orally twice daily (BID). |
| Abiraterone | DRUG | Abiraterone 1000 mg administered orally once daily (QD) in combination with prednisone/prednisolone according to local prescribing information. |
| Prednisone/Prednisolone | DRUG | Oral corticosteroid administered with abiraterone in Phase I Group B according to local prescribing information. |
| Androgen Deprivation Therapy (ADT) | DRUG | Background therapy consisting of a gonadotropin-releasing hormone (GnRH) agonist/antagonist or prior orchiectomy to maintain castrate testosterone levels (\<50 ng/dL \[\<1.7 nmol/L\]). All participants will continue ADT throughout study participation. |
| Tulmimetostat DL1 QD | DRUG | Part 1a (dose escalation): Doses of tulmimetostat beyond DL1 once a day (QD) will be opened depending on outcome of Dose Escalation Meetings (DEM(s)) |
| Tulmimetostat DL2 QD | DRUG | Part 1a (dose escalation): Doses of tulmimetostat beyond DL1 once a day (QD) will be opened depending on outcome of Dose Escalation Meetings (DEM(s)) |
| Tulmimetostat DL3 QD | DRUG | Part 1a (dose escalation): Doses of tulmimetostat beyond DL1 once a day (QD) will be opened depending on outcome of Dose Escalation Meetings (DEM(s)) |
| Tulmimetostat Doses 1 or 2 QD | DRUG | Part 1b (dose expansion and optimization): tulmimetostat doses 1 or 2 QD |
| Tulmimetostat RP2D QD | DRUG | Part 2: tulmimetostat Recommended Phase 2 Dose (RP2D) QD |
| JSB462 Dose 1 QD | DRUG | JSB462 Dose 1 QD |
| JSB462 Dose 2 QD | DRUG | JSB462 Dose 2 QD |
| JSB462 QD | DRUG | The dose of JSB462 QD will be determined based on the totality of data from Part 1a |
| Standard of Care (SoC) | DRUG | Androgen Receptor Pathway Inhibitors (ARPI), chemotherapy or Pluvicto (AAA617) at the discretion of the investigator |
| Enzalutamide | DRUG | Enzalutamide dosed once per day orally in 28 day cycles |
Inclusion Criteria: * Patients with platinum-sensitive recurrent ovarian, fallopian or primary peritoneal cancer (defined as recurrent disease \> 6 months after completing last platinum- based chemotherapy) that are eligible to receive platinum-based chemotherapy). * Documented disease recurrence/p...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 3 | PHASE2 | Pembrolizumab, Gardasil 9 |
| Incyte Corporation | INCY | 1 | PHASE2 | Retifanlimab |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115 |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | Aldesleukin |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |
Tulmimetostat is an investigational small molecule oncology drug being developed by Novartis AG. It is being studied in several cancer types, including advanced solid tumors, metastatic hormone-sensitive prostate cancer, progressive metastatic castrate resistant prostate cancer, recurrent ovarian cancer, and mycosis fungoides. It is currently in Phase 1 clinical development and has not been approved for any indication.
Tulmimetostat is being studied for the treatment of advanced solid tumors, metastatic hormone-sensitive prostate cancer (mHSPC), progressive metastatic castrate resistant prostate cancer (mCRPC), recurrent ovarian cancer, and mycosis fungoides. These are investigational uses in clinical trials, not approved indications. The trials include biomarker-selected patient populations.
Tulmimetostat is developed by Novartis AG, which trades under the ticker NVS. Novartis is running the clinical program, including the TulmiSTAR-01 and TulmiSTAR-02 studies in prostate cancer and a Phase 1 study in mycosis fungoides and Sézary syndrome.
Tulmimetostat is in Phase 1 clinical development. It is an investigational drug and is not FDA approved. The ongoing studies include Phase 1 dose escalation and expansion trials, with one study described as a Phase I/II design. All trials are currently recruiting or active and not yet completed.
Tulmimetostat is being evaluated in four registered trials. NCT07206056 (TulmiSTAR-01) studies it with JSB462 (luxdegalutamide) in progressive mCRPC. NCT07190300 (TulmiSTAR-02) tests it with darolutamide or abiraterone in mHSPC. NCT05944562 studies it in mycosis fungoides and Sézary syndrome, and NCT05942300 combines it with carboplatin in platinum-sensitive recurrent ovarian cancer.
Yes, Tulmimetostat is also known as CPI-0209. Other names used for the drug in study protocols include Tulmimetostat DL1 QD, Tulmimetostat DL1, Tulmimetostat Doses 1 or 2 QD, Tulmimetostat Doses 1 or 2, and Tulmimetostat RP2D QD or RP2D. These refer to the same investigational compound.