What side effects are associated with this type of intervention?

Common treatments for uveal melanoma include PKC inhibitors and tyrosine kinase inhibitors (TKIs). Known side effects of PKC inhibitors like IDE196 can include gastrointestinal issues, fatigue, and liver enzyme abnormalities. TKIs such as crizotinib may cause side effects like nausea, vomiting, diarrhea, liver toxicity, and visual disturbances. Other treatments for uveal melanoma, such as immune checkpoint inhibitors (e.g., pembrolizumab, ipilimumab), can lead to immune-related adverse effects including colitis, dermatitis, and endocrinopathies. It is important to monitor and manage these side effects in collaboration with healthcare providers.

What prior FDA approvals exist?

As of now, there are no specific FDA-approved treatments for Uveal Melanoma that combine a PKC inhibitor and a TKI like IDE196 and crizotinib. However, treatments for metastatic melanoma, including immune checkpoint inhibitors such as pembrolizumab and ipilimumab, have been approved and are used in clinical practice. These treatments focus on enhancing the body's immune response to fight cancer cells. The ongoing study of IDE196 in combination with crizotinib represents an innovative approach targeting specific molecular pathways in Uveal Melanoma.

What other types of research exist?

Promising novel alternatives to IDE196 + crizotinib for Uveal Melanoma patients include pembrolizumab, ipilimumab + nivolumab, and dacarbazine. These treatments are part of the investigator's choice in the referenced study and have shown efficacy in treating metastatic uveal melanoma.

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Other

Darovasertib + Crizotinib for Uveal Melanoma

Phase 2 & 3

Recruiting

Research Sponsored by IDEAYA Biosciences

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

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

ECOG performance status 0 or 1

Must not have

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

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up approximately 4 years

Awards & highlights

No Placebo-Only Group

Summary

This trial is testing a new drug combination (IDE196 and crizotinib) on patients with a specific type of eye cancer that has spread. The goal is to see if this combination can stop or slow down the cancer better than other treatments. Crizotinib has been used in treating various cancers with ALK gene rearrangements, showing high response rates.

Who is the study for?

This trial is for people with metastatic uveal melanoma who are HLA-A*02:01 negative and haven't had systemic therapy for advanced cancer. They should have measurable disease, be able to take the study drugs safely, have good organ function and physical status, and a life expectancy of at least 3 months.

What is being tested?

The trial is testing IDE196 combined with crizotinib against other treatments like pembrolizumab or ipilimumab + nivolumab. It's an open-label study where patients are randomly chosen to receive either the combination or one of the standard therapies.

What are the potential side effects?

Possible side effects include allergic reactions similar to those from biologic drugs or monoclonal antibodies, lung issues such as pneumonitis, infections requiring antibiotics, liver problems due to prior treatments not resolved fully, and complications from CNS metastases.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

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I haven't had systemic therapy for advanced or metastatic disease, but local treatments are okay.

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I am fully active or can carry out light work.

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My cancer is a type of eye melanoma that has spread.

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I do not have the HLA-A*02:01 gene.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

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My side effects from previous cancer treatments are mild or gone.

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I have used CSF before starting the study drug.

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I do not have brain metastases needing steroids or untreated.

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I do not have active adrenal insufficiency, colitis, or inflammatory bowel disease.

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I have had lung inflammation or scarring in the past.

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I am currently on antibiotics for an infection.

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I am not pregnant or breastfeeding.

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I cannot receive standard treatments due to health reasons.

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I do not have any other types of cancer.

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I have not been treated with PKC, MET, or GNAQ/11 inhibitors before.

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I have an active HIV, Hepatitis B, or Hepatitis C infection.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ approximately 4 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~approximately 4 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and approximately 4 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment

Progression-Free Survival (PFS) by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment

Secondary study objectives

Change from baseline over time and between treatment arms in EORTC QLQ-C30

Change from baseline over time and between treatment arms in EuroQoL (EQ)-5D-5L scores

Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment

+5 more

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

3Treatment groups

Experimental Treatment

Active Control

Group I: Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinibExperimental Treatment2 Interventions

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

Group II: Phase 2a Dose Optimization of IDE196 + crizotinibExperimental Treatment2 Interventions

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

Group III: Phase 2a / 2b / 3 Comparator ArmActive Control4 Interventions

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

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Crizotinib

2014

Completed Phase 3

~2960

0 / 15Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

The combination of IDE196 (darovasertib) and crizotinib targets Uveal Melanoma by inhibiting key pathways involved in tumor growth and survival. IDE196 is a protein kinase C (PKC) inhibitor, which disrupts signaling pathways that promote cancer cell proliferation and survival. Crizotinib is a tyrosine kinase inhibitor (TKI) that targets specific enzymes involved in the growth and spread of cancer cells. This dual approach is significant for Uveal Melanoma patients as it aims to block multiple pathways that the cancer cells use to grow and metastasize, potentially leading to more effective treatment outcomes.

Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Ocular side effects of target therapy and immunotherapy in patients with cutaneous malignant melanoma.Merkel cell carcinoma: a review.