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 |
|---|---|---|---|---|---|---|---|---|---|---|---|
| NCT05987332 | IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma | PHASE2 | ACTIVE NOT_RECRUITING | 420 | — | — | Oct 31, 2023 | Jan 15, 2028 | Feb 17, 2026 | 68 | United States, Australia +11 |
| NCT03947385 | Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions | PHASE1 | RECRUITING | 336 | — | — | Jun 28, 2019 | Jun 15, 2027 | Jun 8, 2026 | 15 | United States, Australia +1 |
dose exposure response (safety and efficacy) relationship, plasma concentration profiles and pharmacokinetic (PK) parameters, treatment-emergent Adverse Events (TEAEs), laboratory abnormalities, electrocardiogram (ECG), and vital sign changes and study treatment discontinuation due to AEs.
by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment per RECIST v1.1
OS from randomization to date of death due to any cause
Determine DLT of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Determine MTD of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Determine RP2D of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Pharmacokinetics of IDE196 as monotherapy, in combination with Binimetinib, or in combination with Crizotinib
Pharmacokinetics of Crizotinib in combination with IDE196
Pharmacokinetics of Binimetinib in combination with IDE196
Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 (v1.1) criteria
RECIST v1.1
| Arm | Type | Description |
|---|---|---|
| Phase 2a Dose Optimization of IDE196 + crizotinib | EXPERIMENTAL | Multiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose. |
| Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib | EXPERIMENTAL | Chosen combination dose of IDE196 + crizotinib will be tested in additional participants. |
| Phase 2a / 2b / 3 Comparator Arm | ACTIVE_COMPARATOR | Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine. |
| Dose Escalation Monotherapy (Enrollment Complete) | EXPERIMENTAL | IDE196 dosed orally, twice daily (BID) for each 28-day cycle |
| Dose Expansion Monotherapy (Enrollment Complete) | EXPERIMENTAL | RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors) |
| Dose Escalation Binimetinib Combination (Enrollment Complete) | EXPERIMENTAL | IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle |
| Dose Expansion Binimetinib Combination (Enrollment Complete) | EXPERIMENTAL | RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors) |
| Dose Escalation Crizotinib Combination (Enrollment Complete) | EXPERIMENTAL | IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle |
| Dose Expansion Crizotinib Combination (Enrolling) | EXPERIMENTAL | MUM patients (previously treated or treatment naive) with human leukocyte antigen (HLA)-A\*02:01 positive status. Includes a nested PK sub-study with Pravastatin (\~22 participants) to evaluate the impact of pravastatin PK profiles after continuous dosing of IDE196. Includes a nested PK Cocktail DDI sub-study (\~15 participants) to evaluate the impact on the PK of bupripion, repaglinide, flurbiprofen, omeprazole, midazolam, dabigatran etexilate, and the exposures of the OAT3 biomarker PDA by IDE196 in combination with crizotinib. |
| Dose Optimization Crizotinib Combination (Enrollment Complete) | EXPERIMENTAL | IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle |
| Crizotinib Monotherapy with Crossover to Combination (Enrollment Complete) | EXPERIMENTAL | Crizotinib dosed orally, twice daily (BID) for each 28-day cycle until disease progression then IDE196 added and dosed orally, twice daily (BID) for each 28-day cycle |
| Name | Type | Description |
|---|---|---|
| IDE196 | DRUG | Dosed orally, twice daily |
| Crizotinib | DRUG | Dosed orally, twice daily |
| Pembrolizumab | DRUG | IV administration every 3 weeks |
| Ipilimumab | DRUG | IV administration every 3 weeks for 4 Cycles |
| Nivolumab | DRUG | IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance |
| Dacarbazine | DRUG | IV administration every 3 Weeks |
| Binimetinib | DRUG | Binimetinib dosed orally, twice daily for each 28-day cycle |
Inclusion Criteria: * Histological or cytological confirmed Metastatic Uveal Melanoma * HLA-A\*02:01 negative * No prior systemic therapy in the metastatic or advanced setting regional or liver-directed therapy. Ablations or surgical resection of oligometastatic disease, and neoadjuvant or adjuvant...