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Trial record 1 of 1 for:    05987332
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IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma

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ClinicalTrials.gov Identifier: NCT05987332
Recruitment Status : Recruiting
First Posted : August 14, 2023
Last Update Posted : May 14, 2024
Sponsor:
Information provided by (Responsible Party):
IDEAYA Biosciences

Brief Summary:
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).

Condition or disease Intervention/treatment Phase
Metastatic Uveal Melanoma Drug: IDE196 Drug: Crizotinib Drug: Pembrolizumab Drug: Ipilimumab Drug: Nivolumab Drug: Dacarbazine Phase 2 Phase 3

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 380 participants
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : October 31, 2023
Estimated Primary Completion Date : January 15, 2027
Estimated Study Completion Date : January 15, 2028


Arm Intervention/treatment
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.
Drug: IDE196
Dosed orally, twice daily
Other Name: Darovasertib

Drug: Crizotinib
Dosed orally, twice daily
Other Name: XALKORI

Experimental: Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib
Chosen combination dose of IDE196 + crizotinib will be tested in additional participants.
Drug: IDE196
Dosed orally, twice daily
Other Name: Darovasertib

Drug: Crizotinib
Dosed orally, twice daily
Other Name: XALKORI

Active Comparator: Phase 2a / 2b / 3 Comparator Arm
Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine.
Drug: Pembrolizumab
IV administration every 3 weeks
Other Name: Keytruda

Drug: Ipilimumab
IV administration every 3 weeks for 4 Cycles
Other Name: Yervoy

Drug: Nivolumab
IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance
Other Name: Opdivo

Drug: Dacarbazine
IV administration every 3 Weeks
Other Name: DTIC-Dome




Primary Outcome Measures :
  1. Progression-Free Survival (PFS) by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment [ Time Frame: Approximately 2 years ]
    PFS per RECIST 1.1

  2. Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment [ Time Frame: Approximately 4 years ]
    OS from randomization to date of death due to any cause


Secondary Outcome Measures :
  1. Safety of IDE196 + Crizotinib: Incidence of Adverse Events [ Time Frame: Approximately 2 years ]
    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

  2. Phase 2a: Dose exposure response of IDE196 [ Time Frame: Approximately 5 months ]
    Dose-exposure-response of IDE196 as measured by concentration of IDE196 in plasma

  3. Phase 2a: Dose exposure response of Crizotinib [ Time Frame: Approximately 5 months ]
    Dose-exposure-response of Crizotinib as measured by concentration of Crizotinib in plasma

  4. Progression-Free Survival (PFS) per Investigator of IDE196 + Crizotinib compared to investigator's choice of treatment [ Time Frame: Approximately 2 years ]
    PFS per RECIST 1.1

  5. Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment [ Time Frame: Approximately 2 years ]
    ORR per RECIST 1.1

  6. Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment [ Time Frame: Approximately 2 years ]
    DOR per RECIST 1.1

  7. Change from baseline over time and between treatment arms in EORTC QLQ-C30 [ Time Frame: Approximately 2 years ]
    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.

  8. Change from baseline over time and between treatment arms in EuroQoL (EQ)-5D-5L scores [ Time Frame: Approximately 2 years ]
    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.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT05987332


Contacts
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Contact: IDEAYA Clinical Trials 1 650-534-3616 IDEAYAClinicalTrials@ideayabio.com
Contact: Darrin Beaupre, MD, Ph.D 650-443-6306 dbeaupre@ideayabio.com

Locations
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Sponsors and Collaborators
IDEAYA Biosciences
Investigators
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Study Director: Darrin Beaupre, MD, Ph.D IDEAYA Biosciences
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Responsible Party: IDEAYA Biosciences
ClinicalTrials.gov Identifier: NCT05987332    
Other Study ID Numbers: IDE196-002
First Posted: August 14, 2023    Key Record Dates
Last Update Posted: May 14, 2024
Last Verified: April 2024

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by IDEAYA Biosciences:
IDE196
Darovasertib
Protein Kinase C
Metastatic Uveal Melanoma
Melanoma
Ocular Oncology
Ophthalmology
Crizotinib
Ocular melanoma
Additional relevant MeSH terms:
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Melanoma
Uveal Neoplasms
Neuroendocrine Tumors
Neuroectodermal Tumors
Neoplasms, Germ Cell and Embryonal
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Nerve Tissue
Nevi and Melanomas
Skin Neoplasms
Neoplasms by Site
Skin Diseases
Eye Neoplasms
Eye Diseases
Uveal Diseases
Pembrolizumab
Nivolumab
Ipilimumab
Dacarbazine
Crizotinib
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immune Checkpoint Inhibitors
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Alkylating
Alkylating Agents
Tyrosine Kinase Inhibitors
Protein Kinase Inhibitors
Enzyme Inhibitors