search
Back to results

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

Primary Purpose

Metastatic Uveal Melanoma

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
IDE196
Crizotinib
Pembrolizumab
Ipilimumab
Nivolumab
Dacarbazine
Sponsored by
IDEAYA Biosciences
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Metastatic Uveal Melanoma focused on measuring IDE196, Darovasertib, Protein Kinase C, Metastatic Uveal Melanoma, Melanoma, Ocular Oncology, Ophthalmology, Crizotinib, Ocular melanoma

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Moores Cancer Center
  • UCLA Medical Center
  • The Angeles Clinic and Research Institute
  • California Pacific Medical Center (CPMC)
  • University of California San Francisco
  • SCRI at HealthONERecruiting
  • University of Miami Sylvester Comprehensive Cancer Center
  • Moffitt Cancer Center
  • Northside Hospital Atlanta
  • University of Iowa
  • Massachusetts General Hospital
  • Dana Farber Cancer InstituteRecruiting
  • The Cancer and Hematology CentersRecruiting
  • Roswell Park Cancer Institute
  • Northwell Health
  • Duke University Health System
  • University of Cincinnati
  • The Cleveland Clinic Foundation
  • Thomas Jefferson UniversityRecruiting
  • University of Pittsburgh Medical Center
  • SCRI at Tennessee OncologyRecruiting
  • UT Southwestern Medical Center
  • Houston Methodist Cancer Center
  • MD Anderson Cancer Center
  • Westmead Hospital
  • Princess Alexander Hospital
  • Alfred Health
  • Princess Margaret Cancer Centre

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Active Comparator

Arm Label

Phase 2a Dose Optimization of IDE196 + crizotinib

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

Phase 2a / 2b / 3 Comparator Arm

Arm Description

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.

Outcomes

Primary Outcome Measures

Progression-Free Survival (PFS) by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment
PFS per RECIST 1.1
Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment
OS from randomization to date of death due to any cause

Secondary Outcome Measures

Safety of IDE196 + Crizotinib: Incidence of Adverse Events
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
Phase 2a: Dose exposure response of IDE196
Dose-exposure-response of IDE196 as measured by concentration of IDE196 in plasma
Phase 2a: Dose exposure response of Crizotinib
Dose-exposure-response of Crizotinib as measured by concentration of Crizotinib in plasma
Progression-Free Survival (PFS) per Investigator of IDE196 + Crizotinib compared to investigator's choice of treatment
PFS per RECIST 1.1
Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment
ORR per RECIST 1.1
Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment
DOR per RECIST 1.1
Change from baseline over time and between treatment arms in EORTC QLQ-C30
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.
Change from baseline over time and between treatment arms in EuroQoL (EQ)-5D-5L scores
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.

Full Information

First Posted
July 12, 2023
Last Updated
October 19, 2023
Sponsor
IDEAYA Biosciences
search

1. Study Identification

Unique Protocol Identification Number
NCT05987332
Brief Title
IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma
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)
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2023 (Anticipated)
Primary Completion Date
January 15, 2027 (Anticipated)
Study Completion Date
January 15, 2028 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
IDEAYA Biosciences

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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).
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Metastatic Uveal Melanoma
Keywords
IDE196, Darovasertib, Protein Kinase C, Metastatic Uveal Melanoma, Melanoma, Ocular Oncology, Ophthalmology, Crizotinib, Ocular melanoma

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
380 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Phase 2a Dose Optimization of IDE196 + crizotinib
Arm Type
Experimental
Arm Description
Multiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose.
Arm Title
Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib
Arm Type
Experimental
Arm Description
Chosen combination dose of IDE196 + crizotinib will be tested in additional participants.
Arm Title
Phase 2a / 2b / 3 Comparator Arm
Arm Type
Active Comparator
Arm Description
Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine.
Intervention Type
Drug
Intervention Name(s)
IDE196
Other Intervention Name(s)
Darovasertib
Intervention Description
Dosed orally, twice daily
Intervention Type
Drug
Intervention Name(s)
Crizotinib
Other Intervention Name(s)
XALKORI
Intervention Description
Dosed orally, twice daily
Intervention Type
Drug
Intervention Name(s)
Pembrolizumab
Other Intervention Name(s)
Keytruda
Intervention Description
IV administration every 3 weeks
Intervention Type
Drug
Intervention Name(s)
Ipilimumab
Other Intervention Name(s)
Yervoy
Intervention Description
IV administration every 3 weeks for 4 Cycles
Intervention Type
Drug
Intervention Name(s)
Nivolumab
Other Intervention Name(s)
Opdivo
Intervention Description
IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance
Intervention Type
Drug
Intervention Name(s)
Dacarbazine
Other Intervention Name(s)
DTIC-Dome
Intervention Description
IV administration every 3 Weeks
Primary Outcome Measure Information:
Title
Progression-Free Survival (PFS) by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment
Description
PFS per RECIST 1.1
Time Frame
Approximately 2 years
Title
Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment
Description
OS from randomization to date of death due to any cause
Time Frame
Approximately 4 years
Secondary Outcome Measure Information:
Title
Safety of IDE196 + Crizotinib: Incidence of Adverse Events
Description
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
Time Frame
Approximately 2 years
Title
Phase 2a: Dose exposure response of IDE196
Description
Dose-exposure-response of IDE196 as measured by concentration of IDE196 in plasma
Time Frame
Approximately 5 months
Title
Phase 2a: Dose exposure response of Crizotinib
Description
Dose-exposure-response of Crizotinib as measured by concentration of Crizotinib in plasma
Time Frame
Approximately 5 months
Title
Progression-Free Survival (PFS) per Investigator of IDE196 + Crizotinib compared to investigator's choice of treatment
Description
PFS per RECIST 1.1
Time Frame
Approximately 2 years
Title
Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment
Description
ORR per RECIST 1.1
Time Frame
Approximately 2 years
Title
Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment
Description
DOR per RECIST 1.1
Time Frame
Approximately 2 years
Title
Change from baseline over time and between treatment arms in EORTC QLQ-C30
Description
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.
Time Frame
Approximately 2 years
Title
Change from baseline over time and between treatment arms in EuroQoL (EQ)-5D-5L scores
Description
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.
Time Frame
Approximately 2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
IDEAYA Clinical Trials
Phone
1 650-534-3616
Email
IDEAYAClinicalTrials@ideayabio.com
First Name & Middle Initial & Last Name or Official Title & Degree
Matthew Maurer, MD
Email
mmaurer@ideayabio.com
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Matthew Maurer, MD
Organizational Affiliation
IDEAYA Biosciences
Official's Role
Study Director
Facility Information:
Facility Name
Moores Cancer Center
City
La Jolla
State/Province
California
ZIP/Postal Code
92093
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
UCLA Medical Center
City
Los Angeles
State/Province
California
ZIP/Postal Code
90024
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
The Angeles Clinic and Research Institute
City
Los Angeles
State/Province
California
ZIP/Postal Code
90025
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
California Pacific Medical Center (CPMC)
City
San Francisco
State/Province
California
ZIP/Postal Code
94115
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of California San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94143
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
SCRI at HealthONE
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
SCRI Front Desk
Phone
720-754-2610
Email
cann.ddudenvergeneral@sarahcannon.com
Facility Name
University of Miami Sylvester Comprehensive Cancer Center
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Northside Hospital Atlanta
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30342
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Iowa
City
Iowa City
State/Province
Iowa
ZIP/Postal Code
52242
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Massachusetts General Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02114
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Dana Farber Cancer Institute
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02215
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rizwan Haq
Phone
617-632-6168
Email
rizwan_haq@dfci.harvard.edu
First Name & Middle Initial & Last Name & Degree
Linnea Drew
Phone
617-632-6705
Email
linneam_drew@dfci.harvard.edu
Facility Name
The Cancer and Hematology Centers
City
Grand Rapids
State/Province
Michigan
ZIP/Postal Code
49546
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
The Cancer and Hematology Centers
Phone
616-954-5550
Email
ClinicalTrials@chcwm.com
First Name & Middle Initial & Last Name & Degree
Jessica Miller, RN
Phone
616-954-5550
Ext
1651
Email
Jmiller@chcwm.com
Facility Name
Roswell Park Cancer Institute
City
Buffalo
State/Province
New York
ZIP/Postal Code
14263
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Northwell Health
City
Manhasset
State/Province
New York
ZIP/Postal Code
11030
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Duke University Health System
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45267
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
The Cleveland Clinic Foundation
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44195
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Thomas Jefferson University
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19107
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Marlana Orloff
Phone
215-955-9980
Email
Marlana.Orloff@Jefferson.edu
First Name & Middle Initial & Last Name & Degree
Kristie Hensel
Phone
215-955-9980
Email
Kristie.Hensel@Jefferson.edu
Facility Name
University of Pittsburgh Medical Center
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15232
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
SCRI at Tennessee Oncology
City
Nashville
State/Province
Tennessee
ZIP/Postal Code
37203
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
SCRI Front Desk
Phone
844-482-4812
Facility Name
UT Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Houston Methodist Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
MD Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Not yet recruiting
Facility Name
Westmead Hospital
City
Sydney
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Princess Alexander Hospital
City
Brisbane
State/Province
Queensland
ZIP/Postal Code
4102
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Alfred Health
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3168
Country
Australia
Individual Site Status
Not yet recruiting
Facility Name
Princess Margaret Cancer Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5G 2M9
Country
Canada
Individual Site Status
Not yet recruiting

12. IPD Sharing Statement

Learn more about this trial

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

We'll reach out to this number within 24 hrs