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

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

Melanoma, Cutaneous Malignant

Herbal and Botanical

Chrysanthemum

IDE196 dosed orally, twice daily (BID) for each 28-day cycle

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations or PRKC fusions (cutaneous melanoma, CRC, other solid tumors)

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Binimetinib dosed orally, twice daily (BID) for each 28-day cycle

RP2D in MUM and non-MUM tumors harboring GNAQ/11 mutations (cutaneous melanoma, CRC, other solid tumors)

IDE196 dosed orally, twice daily (BID) for each 28-day cycle and Crizotinib dosed orally, twice daily (BID) for each 28-day cycle

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

IDE196 dosed orally, once on Cycle 1 Day 1; thereafter, twice daily (BID) for each 28-day cycle

IDE196 dosed orally, twice daily for each 28-day cycle

Binimetinib dosed orally, twice daily for each 28-day cycle

Binimetinib

Crizotinib dosed orally, twice daily for each 28-day cycle

Bartosz Chmielowski, MD

Shaheer Khan, MD

Carol A Wiggs

askSARAH

Jordi Ahnert, MD

Melissa Da Ponte

This is a Phase 1/2, multi-center, open-label basket study designed to evaluate the safety and anti-tumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanoma (MUM), cutaneous melanoma, colorectal cancer, and other solid tumors.

Phase 1 (dose escalation - monotherapy) will assess safety, tolerability and pharmacokinetics of IDE196 via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.

Phase 1 Tablet and Food Effect Pharmacokinetic (PK) Substudy will assess the PK profile of IDE196 tablet and evaluate the effects of food on the PK profile of IDE196 tablet

Phase 1 (dose escalation - binimetib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and binimetinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.

Phase 1 (dose escalation - crizotinib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and crizotinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study. Evaluation of safety and efficacy across multiple doses may be explored in the dose optimization part of the study.

Crizotinib monotherapy with crossover to combination cohort may be assessed for safety and to show the contribution of each study drug to anti-tumor activity.

Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions

A Phase 1/2 Study of IDE196 in Patients With Solid Tumors Harboring GNAQ/11 Mutations or PRKC Fusions

From date of First Dose to End of Follow-up

Maximum reduction in tumor burden relative to response

Modulation of gene signatures and/or molecular profiles

Modulation of tissue or cell-free DNA expression

Determine DLT of IDE196 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

Safety and tolerability of IDE196 either as monotherapy, in combination with Binimetinib, or in combination with Crizotinib

Modulation of signaling proteins in PKC, MAPK, and MET pathways

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
(Neo)Adjuvant IDE196 (Darovasertib) in Patients With Localized Ocular Melanoma	NCT05907954	Uveal Melanoma	Darovasertib	18 Years -	IDEAYA Biosciences
(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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