Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Tulmimetostat · 3 trials · 12 indications
A dose-limiting toxicity is defined as an adverse event or abnormal laboratory value, not clearly due to underlying disease or extraneous causes, that occurs within the first 28 days of treatment with tulmimetostat 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
Duration of exposure (in months) to each study drug will be summarized by means of descriptive statistics
Prostate-Specific Antigen (PSA) response rate is defined as proportion of participants who achieved a decline in PSA to \< 0.2 ng/mL at month 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 |
|---|---|---|
| Phase I: Group A (part 1) | EXPERIMENTAL | Tulmimetostat oral (PO) once a day (QD) escalating doses + Darolutamide 600 mg twice a day (BID) |
| Phase I: Group B (part 2) | EXPERIMENTAL | Tulmimetostat PO QD escalating doses + Abiraterone 1000 mg PO QD |
| Phase II: Arm 1 | EXPERIMENTAL | Tulmimetostat dose 1 PO + Darolutamide 600 mg PO BID |
| Phase II: Arm 2 | EXPERIMENTAL | Tulmimetostat dose 2 PO + Darolutamide 600 mg PO BID |
| Phase II: Arm 3 | ACTIVE_COMPARATOR | Darolutamide 600 mg PO BID |
| 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 |
|---|---|---|
| Tulmimetostat | DRUG | Doses of tulmimetostat beyond DL1 once a day (QD) will be opened depending on outcome of Dose Escalation Meetings (DEM(s)) |
| Darolutamide | DRUG | 600 mg is administered orally BID |
| Abiraterone | DRUG | 1000 mg is administered orally QD |
| Enzalutamide | DRUG | Enzalutamide dosed once per day orally in 28 day cycles |
Key Inclusion Criteria: * Adult men ≥ 18 years old with de novo or recurrent mHSPC (without neuroendocrine or small cell features). The tumor lesion(s) may be located in the bone, soft tissue/visceral region, or both. * Participants must have castrate levels of testosterone, i.e., ≤ 50 ng/dL (≤ 1.7...
| Company | Ticker | Trials | Lead Phase | Drugs |
|---|---|---|---|---|
| Merck & Co., Inc. | MRK | 2 | PHASE2 | pembrolizumab |
| Incyte Corporation | INCY | 1 | PHASE2 | Chemotherapy, Retifanlimab |
| Iovance Biotherapeutics Inc | IOVA | 2 | PHASE2 | E7 TCR-T cells, Aldesleukin |
| Novartis AG Sponsored ADR | NVS | 1 | PHASE1 | KFA115, pembrolizumab |
| AstraZeneca PLC | AZN | 1 | - | Trastuzumab deruxtecan |
Tulmimetostat is an investigational small molecule being studied in oncology for advanced solid tumors, mycosis fungoides, and metastatic hormone-sensitive prostate cancer (mHSPC). It is also being evaluated in lymphomas and other cancer types. The drug is in Phase 1 clinical development.
Tulmimetostat is an enzyme inhibitor, belonging to the -stat class of drugs. It is being studied for its effects on cancer cell growth in solid tumors and lymphomas. The specific molecular target is not disclosed in the available information.
Tulmimetostat is being developed by Novartis AG, a global pharmaceutical company listed on the New York Stock Exchange under the ticker NVS. The drug is currently in Phase 1 clinical trials for multiple oncology indications.
Tulmimetostat is in Phase 1 clinical development. It is an investigational drug and has not been approved by regulatory authorities. Multiple Phase 1 trials are ongoing or have been completed to evaluate its safety and efficacy in various cancers.
Tulmimetostat is being studied in several clinical trials. NCT04104776 is a Phase 1 study in advanced solid tumors and lymphomas. NCT05944562 is a Phase 1 trial in mycosis fungoides and Sézary syndrome. NCT07190300 is a Phase 1/II study in metastatic hormone-sensitive prostate cancer.
Yes, Tulmimetostat is also known as DZR123 and CPI-0209. These names refer to the same investigational drug being developed by Novartis. In clinical trial records, the drug is sometimes listed under these alternative identifiers.