Approval Probability 71%
TA Base Rate26%
Adjusted LOA41%
ML RiskLOW_RISK
| NCT ID | Title | Phase | Status | Enrollment | Velocity | Design | Start | Completion | Last Updated | Sites | Countries |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT05617885 | Neo-DAB: Darolutamide and Abemaciclib in Prostate Cancer | PHASE1 | ACTIVE NOT_RECRUITING | 9 | — | — | Aug 9, 2023 | Jun 1, 2026 | Feb 27, 2026 | 1 | United States |
The Maximum Tolerated Dose (MTD) for the study drug combination is defined as the maximum dose combination at which \<33% of patients experience a Dose limiting toxicity (DLT) during Cycle 1 (the DLT-evaluation period). If a DLT is observed in 1 of 3 patients, then 3 additional patients will be enrolled at that same dose level. Dose escalation will continue to a dose of abemaciclib 200mg bid, which is the maximal dose levels. If DLTs are seen in 0-1 of 6 patients at dose level +1 (darolutamide 600mg bid and abemaciclib 200mg bid), then this will be the RP2D; otherwise the maximally tolerated dose (MTD) will be the RP2D.
Dose Limiting Toxicity (DLT) for Phase 1 is defined as an adverse event that is related to Darolutamide and Abemaciclib with an attribution of possible, probable or definite and occurs during and/or begins during the first 28 days of the study treatment, using NCI CTCAE criteria version 5.0.
RP2D will be determined after an Maximum Tolerated Dose (MTD) is identified or the maximum planned dose is achieved. Recommended Phase 2 Dose (RP2D) is defined as no more than 0-1 patients with dose limiting toxicity out of 6 at maximal dose level. Otherwise, the maximally tolerated dose will be used.
Pathologic response is defined as achieving either a complete response (pCR) or minimal residual disease (MRD, defined as ≤5mm residual tumor) at Radical Prostatectomy (RP) in both arms
| Arm | Type | Description |
|---|---|---|
| Phase 1 Lead In in CRPC | EXPERIMENTAL | Standard 3+3 dose escalation scheme with 3 dose levels of abemaciclib and a constant dose of darolutamide, per protocol, for 6, 28-day cycles |
| Phase 2 - Neoadjuvant Darolutamide and ADT prior to Radical Prostatectomy | EXPERIMENTAL | per protocol, for 6, 28-day cycles |
| Phase 2 - Neoadjuvant Darolutamide, Ademaciclib, and ADT prior to Radical Prostatectomy | EXPERIMENTAL | per protocol, for 6, 28-day cycles |
| Name | Type | Description |
|---|---|---|
| Darolutamide | DRUG | Tablet administered orally, per protocol, 2 x daily. Darolutamide is an orally administered molecular drug therapy that blocks the action of testosterone, the male sex hormone which can stimulate growth of prostate cancer. |
| Abemaciclib | DRUG | Tablet administered orally, per protocol, 2 x daily. Abemaciclib is an orally administered molecular drug therapy that is called a "CDK4/6 inhibitor". CDK4 and CDK6 are enzymes that are involved in helping healthy and cancerous cells divide and blocking these enzymes can stop cancerous cells from growing. |
| GNRH-A Leuprolide Acetate | DRUG | Administered via intramuscular injection, per standard of care. GnRH agonist is a hormonal therapy drug. |
| GNRH-A Goserelin | DRUG | Administered via subcutaneous injection, per standard of care. GnRH agonist is a hormonal therapy drug. |
| Degarelix | DRUG | Administered via subcutaneous injection, per standard of care. GnRH antagonist is a hormonal therapy drug. |
Inclusion Criteria For Phase 1: * Provision of signed informed consent prior to any study specific procedures, or have a legally authorized representative sign on the participant's behalf. * Ability to swallow oral medications and comply with study procedures and requirements. * Males ≥18 years * H...