IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma

Study Purpose

This is a Phase 2/3, multi-arm, multi-stage, open-label study of human leukocyte antigen (HLA)-A*02:01 negative participants with metastatic uveal melanoma (MUM) who will be randomized to receive either IDE196 + crizotinib or investigator's choice of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine).

Recruitment Criteria

Accepts Healthy Volunteers Healthy volunteers are participants who do not have a disease or condition, or related conditions or symptoms	No
Study Type An interventional clinical study is where participants are assigned to receive one or more interventions (or no intervention) so that researchers can evaluate the effects of the interventions on biomedical or health-related outcomes. An observational clinical study is where participants identified as belonging to study groups are assessed for biomedical or health outcomes. Searching Both is inclusive of interventional and observational studies.	Interventional
Eligible Ages	18 Years and Over
Gender	All

More Inclusion & Exclusion Criteria

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, or neoadjuvant or adjuvant therapy is allowed.

- Measurable disease per RECIST 1.1.

- Able to be safely administered and absorb study therapy.

- ECOG performance status 0 or 1.

- Life expectancy of ≥3 months.

- Adequate organ function.

Exclusion Criteria:

- Previous treatment with a PKC inhibitor (including prior treatment with IDE196), an inhibitor directly targeting MET, or an inhibitor directly targeting GNAQ/11.

- Concurrent malignant disease.

- AEs from prior anti-cancer therapy that have not resolved to Grade ≤1.

- Symptomatic or untreated central nervous system (CNS) metastases, or CNS metastases that require corticosteroids.

- Active HIV infection or Hep B/C.

- Active adrenal insufficiency, active colitis, or active inflammatory bowel disease.

- History of interstitial lung disease, active pneumonitis, or history of pneumonitis.

- Active infection requiring systemic antibiotic therapy.

- Use of hematopoietic colony-stimulating factors (CSF) prior to start of study drug.

- Females who are pregnant or breastfeeding.

- History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies.

- Contraindication for treatment with investigator's choice therapies as per applicable labelling.

- Has any other condition that may increase the risk associated with study participation or may interfere with the interpretation of study results and, in the opinion of the investigator, would make the participant inappropriate for entry into the study

Trial Details

Trial ID: This trial id was obtained from ClinicalTrials.gov, a service of the U.S. National Institutes of Health, providing information on publicly and privately supported clinical studies of human participants with locations in all 50 States and in 196 countries.	NCT05987332
Phase Phase 1: Studies that emphasize safety and how the drug is metabolized and excreted in humans. Phase 2: Studies that gather preliminary data on effectiveness (whether the drug works in people who have a certain disease or condition) and additional safety data. Phase 3: Studies that gather more information about safety and effectiveness by studying different populations and different dosages and by using the drug in combination with other drugs. Phase 4: Studies occurring after FDA has approved a drug for marketing, efficacy, or optimal use.	Phase 2/Phase 3
Lead Sponsor The sponsor is the organization or person who oversees the clinical study and is responsible for analyzing the study data.	IDEAYA Biosciences
Principal Investigator The person who is responsible for the scientific and technical direction of the entire clinical study.	Darrin Beaupre, MD, Ph.D
Principal Investigator Affiliation	IDEAYA Biosciences
Agency Class Category of organization(s) involved as sponsor (and collaborator) supporting the trial.	Industry
Overall Status	Recruiting
Countries	Australia, Belgium, Canada, France, Germany, Israel, Italy, Netherlands, Poland, Spain, Switzerland, United Kingdom, United States
Conditions The disease, disorder, syndrome, illness, or injury that is being studied.	Metastatic Uveal Melanoma

Additional Details

This study is designed as a multi-stage Phase 2 study within a Phase 3 study to evaluate the safety, tolerability, pharmacokinetics, dose-exposure relationship, and anti-tumor activity of IDE196 in combination with crizotinib compared to the comparator arm of investigator's choice of treatment (pembrolizumab, ipilimumab + nivolumab, or dacarbazine). The Phase 2a dose optimization stage will evaluate two doses of IDE196 in combination with crizotinib compared to the comparator arm. Participants will be randomized to the three treatment arms. At the point of optimal IDE196 + crizotinib dose selection, the other dose arm will be dropped with discontinuation of enrollment to that arm. Participants receiving the IDE196 dose (in combination with crizotinib) that is not selected, will be offered the choice to remain on the same dose or change to the chosen optimal dose. The optimal dose will be chosen to complete the Phase 2b portion. The Phase 2b part of the study will continue to enroll the chosen combination dose of IDE196 + crizotinib compared with the comparator arm. Participants will be randomized to the two treatment arms. The Phase 3 part of the study will continue to enroll the chosen combination dose of IDE196 + crizotinib compared with the comparator arm. Participants will be randomized to the two treatment arms.

Arms & Interventions

Arms

Experimental: Phase 2a Dose Optimization of IDE196 + crizotinib

Multiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose.

Experimental: Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib

Chosen combination dose of IDE196 + crizotinib will be tested in additional participants.

Active Comparator: Phase 2a / 2b / 3 Comparator Arm

Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine.

Interventions

Drug: - IDE196

Dosed orally, twice daily

Drug: - Crizotinib

Dosed orally, twice daily

Drug: - Pembrolizumab

IV administration every 3 weeks

Drug: - Ipilimumab

IV administration every 3 weeks for 4 Cycles

Drug: - Nivolumab

IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance

Drug: - Dacarbazine

IV administration every 3 Weeks

Contact a Trial Team

If you are interested in learning more about this trial, find the trial site nearest to your location and contact the site coordinator via email or phone. We also strongly recommend that you consult with your healthcare provider about the trials that may interest you and refer to our terms of service below.

Honor Health, Scottsdale, Arizona

Status

Recruiting

Address

Honor Health

Scottsdale, Arizona, 85258

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