Approval Probability
TA Base Rate
Adjusted LOA
ML Risk
Also known as IDE196, LXS196
Darovasertib · 5 trials · 5 indications
Time to local recurrence or metastatic disease per Blinded Independent Central Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1)
Loss of Best Corrected Visual Acuity (BCVA) of ≥ 15 letters using Early Treatment Diabetic Retinopathy Study (ETDRS) BCVA
Eye preservation rate
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
Treatment emergent adverse events will be summarized by all AEs, all Grade 3-4-5 AEs, all treatment related AEs, all AEs leading to study drug modifications or discontinuations, all SAEs. Lab results will be summarized by change from baseline values, frequency of newly occurring on-treatment Grade 3 or 4 events; worst on-treatment value compared to baseline.
Rate of eye salvage as determined by the ocular oncologist based on tumor response to neoadjuvant therapy
Change in modeled radiation dose at critical eye structures before and after neoadjuvant therapy
Proportion of patients with clinical benefit rate (CBR) defined as complete response (CR) + partial response (PR) + stable disease (SD) for ≥ 12 weeks per UM response criteria
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 |
|---|---|---|
| Treatment | EXPERIMENTAL | Participant Group/Arm: Treatment combination dose of IDE196 + crizotinib will be tested |
| Observation | NO_INTERVENTION | Participant Group/Arm: Observation Standard of care observation \& follow-up (no treatment) |
| Treatment Arm | EXPERIMENTAL | Darovasetib followed by definitive primary local therapy (i.e., PB, proton beam radiation, or enucleation) |
| Control Arm | ACTIVE_COMPARATOR | Immediate Primary Local therapy |
| 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. |
| darovasertib | EXPERIMENTAL | IDE196 (darovasertib) oral open label |
| 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 |
|---|---|---|
| Darovasertib | DRUG | Oral, selectively targets key proteins |
| Crizotinib (Xalkori) | DRUG | Oral small molecule |
| Primary Local Therapy | PROCEDURE | Plaque Brachytherapy or Enucleation |
| 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: * Primary Uveal Melanoma, classified as high-risk of relapse (AJCC Stage II or Stage 3) * Completed primary local therapy (enucleation, proton beam therapy, plaque brachytherapy) * ECOG performance status of 0 or 1 * Adequate organ function * Age 18 or older * Written informed c...
Darovasertib is an investigational small molecule being developed for uveal melanoma, including metastatic uveal melanoma. It is being studied both as a first-line combination therapy in the metastatic setting and in the neoadjuvant and adjuvant settings for primary, non-metastatic uveal melanoma. It has received Breakthrough Therapy and Orphan Drug designations from the FDA.
Darovasertib targets protein kinase C, or PKC. It is a small molecule designed to inhibit PKC signaling, a pathway relevant to uveal melanoma biology. In clinical studies it is being evaluated both as a single agent and in combination with crizotinib.
Darovasertib is being developed by IDEAYA Biosciences, Inc., which trades on the Nasdaq under the ticker IDYA. The company is running the clinical program across metastatic and localized uveal melanoma settings.
Darovasertib is in Phase 2 and Phase 3 clinical development and is not approved. Two Phase 3 trials are recruiting: one evaluating adjuvant darovasertib plus crizotinib in primary non-metastatic uveal melanoma, and one evaluating neoadjuvant darovasertib in primary uveal melanoma.
Darovasertib is being studied in four registered trials. NCT07804186 is a Phase 3 adjuvant study with crizotinib in non-metastatic uveal melanoma. NCT07015190 is a Phase 3 neoadjuvant study in primary uveal melanoma. NCT05987332 is a Phase 2 first-line metastatic study with crizotinib, and NCT05907954 is a Phase 2 (neo)adjuvant study in localized ocular melanoma.
Yes, Darovasertib is also known as IDE196. IDE196 was the earlier code name used for the compound, and it still appears in the titles of several clinical trials, including NCT05987332 and NCT05907954. Both names refer to the same PKC-targeting small molecule developed by IDEAYA Biosciences.