Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Eye Diseases

Rare Diseases

Melanoma

Uveal Neoplasms

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Eye Neoplasms

Uveal Diseases

Ocular Melanoma

Intraocular Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Nivolumab

Pembrolizumab

Ipilimumab

Dacarbazine

Crizotinib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Antineoplastic Agents, Alkylating

Alkylating Agents

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

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

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

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

IDE196

IV administration every 3 weeks for 4 Cycles

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

IDEAYA Clinical Trials

Darrin Beaupre, MD, Ph.D

Oncology Clinical Trials Nurse Navigator

Katie O'Neil, BA

Jazelle Molina

Adyel Annelus

Elizabeth Seja

Saba Mukarram

Denise Fortun

CPMC Clinical Research Group

Sonia Contreras Martinez, BSN

Sarah Mayer, BA

Victoria Mayer, VA

SCRI Front Desk

Nikhil Khushalani, MD

Leticia Tetteh, BSN

Central Research Department

Asad Javed, MD

Kamaneh Montazeri, MD

Rizwan Haq

Linnea Drew

The Cancer and Hematology Centers

Jessica Miller, RN

Amer Alyasiry, MHS

Tyler Klein

Benjamin Switzer, DO

igor Puzanov, MD

Richard Carvajal, MD

Tracy Green, BS

Alexander Shoushtari, MD

James Smithy, MD

Carol Ann Wiggs, BSN

Emily Bolch

Lucy Kennedy, MD

Marlana Orloff

Kristie Hensel

Amy Rose, RN,BSN

Jennifer Cleric, ND, RN

Sanjay Chandrasekaran, MD

Desiree Pierre, BS

Sapna Patel, MD

Matteo Carlino, MD

Janine Thomas

Joanne Tonkin

Rose McDowell

Roberts-Thomson, MD

Jean Francois Baurain, MD

John Walker, MD,PhD,FRCPC

Marcus Butler

Rahima Jamal, MD

Chantal Gosselin

Eve-Marie Neidhardt, MD

Sophie Piperno-Neumann, MD

Jessica Hassel, Prof. Dr. med

Halime Kalkavan, Dr. med

Nicole Kreuzberg, MD

Friedegund Meier, Prof. Dr. med

Caroline Anna Peuker, MD

Jonathan Cohen, MD

Annaelle Dynovisz, SC

Ronnie Shapira, MD

Lorenza DiGuardo, MD

Paolo Ascierto, MD

Ernesto Rossi, MD

Michele Maio, MD

Ellen Kapiteijn, MD

Josep Maria Piulats, MD

Yolanda Alvarez, BSc

Estiban Mendez, Bsc

María del Carmen Álamo, MD

María Candón, SC

Alfonso Berrocal, MD

Iris Ramos

Reinhard Dummer, Prof. Dr. med

Ruth Orr

Joseph Sacco, Professor

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).

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.

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

IDE196 (Darovasertib) in Combination With Crizotinib Versus Investigator's Choice of Treatment as First-line Therapy in HLA-A2 Negative Metastatic Uveal Melanoma (DAR-UM-2)

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 as measured by CTCAE V5.0

Dose-exposure-response of IDE196 as measured by concentration of IDE196 in plasma

Dose-exposure-response of Crizotinib as measured by concentration of Crizotinib in plasma

Global health status and quality of life will be assessed using the EORTC QLQ-C30 questionnaire. The score range for the EORTC QLQ-C30 is from 0 to 100, with higher scores indicating better functioning and better global health status and health-related quality of life. A positive change indicates improvement.

General health status will be assessed using the EQ-5D,5L questionnaire, which includes five dimensions (5D): mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each dimension has 3 scoring levels, where 1 indicates a better health state (no problems) and 3 indicates a worse health state. A positive change indicates improvement.

IDEAYA Biosciences

Patch of umbilical cord lining membrane sutured on top of the scleral defect.

Chemically-treated, viro-inactivated, freeze-dried and irradiated umbilical cord lining membrane allograft used as substitute for scleral graft in reinforcement of scleral thinning.

SclerFIX

Laurence BARNOUIN, MD

Justine BOSC, MSc

Thibaud Mathis, MD

Sacha NAHON-ESTEVE, MD

Jean-Pierre CAUJOLLE, MD

Célia MASCHI, MD

The purpose of this open, multicenter phase II trial is to confirm the tolerance and evaluate the efficacy of the SclerFIX product, an allograft of umbilical cord lining membrane, in reinforcement of scleral thinning in patients who underwent eye tumor exeresis.

As scleral graft is forbidden in France, it cannot be used to reinforce the sclera. This study investigational product, SclerFIX, was developed to substitute scleral grafts.

Evaluation of SclerFIX Graft in Scleral Thinning After Exeresis of Tumors of the Ocular Surface

Phase II Study: Evaluation of SclerFIX Graft in Scleral Thinning After Exeresis of Tumors of the Ocular Surface

The graft will be considered successful at 3 months if the curvature of the eye is respected without thinning, i.e., in the absence of edema, ulceration and loss of substance (thickness of the grafted area/thickness of the adjacent surface \> 80%). The scleral thickness will be determined from images obtained by optical coherence tomography (OCT).

Composite score evaluating the presence of local reactions (edema, redness, vascularization, discharge) and of ulceration, pain and foreign body sensation (0: excellent local tolerance, 46: worst possible local tolerance)

Scoring of blurred and poor vision (0: never, 4: all the time)

Measure of eye pressure using a tonometer

TBF Genie Tissulaire

Oral, potent, selective inhibitor of Protein Kinase C

Darovasertib

Jasgit Sachdev, MD

Claire A Billman, B.S

Denise Haas, MBA

Sarah Cannon

Clinical Trials Group

The Cancer and Hematology Centers of Western Michigan

Leila Nasr, BS

Marlana Orloff, MD

Liam Hulse, BS

Ask Sarah

James Harbour, MD

Juan Mo, PhD

Chris Brooks

Marcus Butler, MD

Neoadjuvant/adjuvant IDE196 (darovasertib) in patients with primary uveal melanoma

Phase 2 multi-center open-label IDE196 study in patients with primary uveal melanoma requiring either enucleation or plaque brachytherapy. Patients will be treated in neoadjuvant setting up to 6 months (or maximum benefit) followed by primary local therapy. An additional 6 months of adjuvant treatment to follow with long term follow-up (up to 3 years) to assess visual outcome, disease recurrence, and development of metastatic disease.

(Neo)Adjuvant IDE196 (Darovasertib) in Patients With Localized Ocular Melanoma

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

Measurement of tumor diameter and thickness before and after neoadjuvant therapy with IDE196, specifically as measured by ocular ultrasound, evaluating largest basal diameter and apical thickness of the uveal melanoma (measured in millimeters)

Best corrected visual acuity loss over time

Evaluate uveal melanoma progression or recurrence

Evaluate occurrence of metastatic uveal melanoma

Diseases and Abnormalities at or Before Birth

Retinoblastoma

Neoplasms, Neuroepithelial

Neoplasms, Glandular and Epithelial

Retinal Neoplasms

Eye Diseases, Hereditary

Retinal Diseases

Jesse L Berry, MD

Jesse Berry, MD

Retinoblastoma (RB) is a primary eye cancer that forms in the back of the eye of infants and toddlers. Traditionally, RB is diagnosed without a biopsy; tumor can only be studied once an eye has been surgically removed.

Given this limitation, we use aqueous humor (AH), the clear fluid in the front of the eye to detect specific markers, or information, that comes from the tumor itself.

Retinoblastoma (RB) is a primary intraocular malignancy that forms in the retina of infants and toddlers. Traditionally, RB is diagnosed without tissue as direct tumor biopsy is prohibited due to risk of extraocular spread; tissue can only be obtained once an eye has been surgically removed.

Given this limitation, there are no eye-specific molecular biomarkers in current clinical practice for RB. The lack of in vivo molecular data without removing the eye limits our ability to prognosticate clinical outcomes and develop personalized treatment plans. It also limits our understanding of intratumoral dynamics throughout therapy.

The aqueous humor (AH) is a high-yield source of tumor-derived nucleic acid that can be utilized as a liquid biopsy in eyes with retinoblastoma. Detection of biomarkers from the AH may be used to prognosticate the likelihood of eye salvage and in the future may facilitate targeted, patient-centered therapies based on molecular biomarkers.

OBJECTIVES:

1. Systematically and prospectively record accurate and complete data regarding the clinical presentation, treatment, and outcomes of patients diagnosed with RB.
2. Collect, bank, preserve, and analyze biomaterials including AH, blood and saliva from patients with RB.
3. Correlate phenotypic data with genotypic findings from human biomaterials in retinoblastoma patients to identify clinically relevant biomarkers

RB Liquid Biopsy Biorepository

Retinoblastoma Patient Clinical Database, Liquid Biopsy and Tissue Biorepository

De-identified data will be available to other researchers via NIH GDS/dbGAP controlled databases.

We aim to evaluate whether any identifiable molecular biomarkers (e.g. chromosomal alterations or tumor fraction) in the aqueous or blood can predict ocular salvage, or the likelihood of saving the eye with therapy

We aim to identify both somatic and germline RB1 gene mutations in the AH

We aim to evaluate whether any identifiable molecular biomarkers in the aqueous or blood can predict the presence of high risk histopathologic features that are known to increase risk of metastatic disease

We aim to evaluate whether any identifiable molecular biomarkers in the aqueous or blood are associated with the presence of type of seeding

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma	NCT05987332	Metastatic Uvea...	IDE196 Crizotinib Pembrolizumab Ipilimumab Nivolumab Dacarbazine	18 Years -	IDEAYA Biosciences
Evaluation of SclerFIX Graft in Scleral Thinning After Exeresis of Tumors of the Ocular Surface	NCT05302609	Scleral Thinnin...	SclerFIX	18 Years - 80 Years	TBF Genie Tissulaire
(Neo)Adjuvant IDE196 (Darovasertib) in Patients With Localized Ocular Melanoma	NCT05907954	Uveal Melanoma	Darovasertib	18 Years -	IDEAYA Biosciences
RB Liquid Biopsy Biorepository	NCT04959097	Retinoblastoma Retinoblastoma ... Retinoblastoma ...		0 Years - 18 Years	Children's Hospital Los Angeles
(Neo)Adjuvant IDE196 (Darovasertib) in Patients With Localized Ocular Melanoma	NCT05907954	Uveal Melanoma	Darovasertib	18 Years -	IDEAYA Biosciences
Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions	NCT03947385	Metastatic Uvea... Cutaneous Melan... Colorectal Canc... Other Solid Tum...	IDE196 Binimetinib Crizotinib	18 Years -	IDEAYA Biosciences

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