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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05987332




Registration number
NCT05987332
Ethics application status
Date submitted
12/07/2023
Date registered
14/08/2023
Date last updated
11/06/2024

Titles & IDs
Public title
IDE196 (Darovasertib) in Combination With Crizotinib as First-line Therapy in Metastatic Uveal Melanoma
Scientific 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)
Secondary ID [1] 0 0
IDE196-002
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Metastatic Uveal Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma
Cancer 0 0 0 0
Other cancer types
Eye 0 0 0 0
Diseases / disorders of the eye

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IDE196
Treatment: Drugs - Crizotinib
Treatment: Drugs - Pembrolizumab
Treatment: Drugs - Ipilimumab
Treatment: Drugs - Nivolumab
Treatment: Drugs - Dacarbazine

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.

Experimental: Phase 2b / 3 Chosen Combination dose of IDE196 + crizotinib - Chosen combination dose of IDE196 + crizotinib will be tested in additional participants.

Active comparator: Phase 2a / 2b / 3 Comparator Arm - Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine.


Treatment: Drugs: IDE196
Dosed orally, twice daily

Treatment: Drugs: Crizotinib
Dosed orally, twice daily

Treatment: Drugs: Pembrolizumab
IV administration every 3 weeks

Treatment: Drugs: Ipilimumab
IV administration every 3 weeks for 4 Cycles

Treatment: Drugs: Nivolumab
IV administration every 3 Weeks for 4 Cycles, thereafter every 4 Weeks maintenance

Treatment: Drugs: Dacarbazine
IV administration every 3 Weeks
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Progression-Free Survival (PFS) by blinded independent central review (BICR) of IDE196 + Crizotinib compared to investigator's choice of treatment
Timepoint [1] 0 0
Approximately 2 years
Primary outcome [2] 0 0
Overall Survival (OS) of IDE196 + Crizotinib compared to investigator's choice of treatment
Timepoint [2] 0 0
Approximately 4 years
Secondary outcome [1] 0 0
Safety of IDE196 + Crizotinib: Incidence of Adverse Events
Timepoint [1] 0 0
Approximately 2 years
Secondary outcome [2] 0 0
Phase 2a: Dose exposure response of IDE196
Timepoint [2] 0 0
Approximately 5 months
Secondary outcome [3] 0 0
Phase 2a: Dose exposure response of Crizotinib
Timepoint [3] 0 0
Approximately 5 months
Secondary outcome [4] 0 0
Progression-Free Survival (PFS) per Investigator of IDE196 + Crizotinib compared to investigator's choice of treatment
Timepoint [4] 0 0
Approximately 2 years
Secondary outcome [5] 0 0
Objective Response Rate (ORR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment
Timepoint [5] 0 0
Approximately 2 years
Secondary outcome [6] 0 0
Duration of Response (DOR) per BICR and Investigator assessment of IDE196 + Crizotinib compared to investigator's choice of treatment
Timepoint [6] 0 0
Approximately 2 years
Secondary outcome [7] 0 0
Change from baseline over time and between treatment arms in EORTC QLQ-C30
Timepoint [7] 0 0
Approximately 2 years
Secondary outcome [8] 0 0
Change from baseline over time and between treatment arms in EuroQoL (EQ)-5D-5L scores
Timepoint [8] 0 0
Approximately 2 years

Eligibility
Key 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
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 2
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
31/10/2023
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
15/01/2028
Actual
Sample size
Target
380
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Westmead Hospital - Sydney
Recruitment hospital [2] 0 0
Princess Alexander Hospital - Brisbane
Recruitment hospital [3] 0 0
Alfred Health - Melbourne
Recruitment hospital [4] 0 0
Sir Charles Gairdner Hospital - Perth
Recruitment hospital [5] 0 0
Queen Elizabeth Hospital - Adelaide
Recruitment postcode(s) [1] 0 0
2145 - Sydney
Recruitment postcode(s) [2] 0 0
4102 - Brisbane
Recruitment postcode(s) [3] 0 0
3168 - Melbourne
Recruitment postcode(s) [4] 0 0
6009 - Perth
Recruitment postcode(s) [5] 0 0
- Adelaide
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Arizona
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
Colorado
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Iowa
Country [7] 0 0
United States of America
State/province [7] 0 0
Massachusetts
Country [8] 0 0
United States of America
State/province [8] 0 0
Michigan
Country [9] 0 0
United States of America
State/province [9] 0 0
Minnesota
Country [10] 0 0
United States of America
State/province [10] 0 0
Missouri
Country [11] 0 0
United States of America
State/province [11] 0 0
New York
Country [12] 0 0
United States of America
State/province [12] 0 0
North Carolina
Country [13] 0 0
United States of America
State/province [13] 0 0
Ohio
Country [14] 0 0
United States of America
State/province [14] 0 0
Pennsylvania
Country [15] 0 0
United States of America
State/province [15] 0 0
Tennessee
Country [16] 0 0
United States of America
State/province [16] 0 0
Texas
Country [17] 0 0
Belgium
State/province [17] 0 0
Brussels
Country [18] 0 0
Canada
State/province [18] 0 0
Alberta
Country [19] 0 0
Canada
State/province [19] 0 0
Ontario
Country [20] 0 0
Canada
State/province [20] 0 0
Quebec
Country [21] 0 0
France
State/province [21] 0 0
Lyon
Country [22] 0 0
France
State/province [22] 0 0
Paris
Country [23] 0 0
Germany
State/province [23] 0 0
Baden- Württemberg
Country [24] 0 0
Germany
State/province [24] 0 0
North Rhine-Westphalia
Country [25] 0 0
Germany
State/province [25] 0 0
Saxony
Country [26] 0 0
Germany
State/province [26] 0 0
Berlin
Country [27] 0 0
Israel
State/province [27] 0 0
Jerusalem
Country [28] 0 0
Israel
State/province [28] 0 0
Ramat-Gan
Country [29] 0 0
Italy
State/province [29] 0 0
Milano
Country [30] 0 0
Italy
State/province [30] 0 0
Napoli
Country [31] 0 0
Italy
State/province [31] 0 0
Roma
Country [32] 0 0
Italy
State/province [32] 0 0
Siena
Country [33] 0 0
Netherlands
State/province [33] 0 0
Leiden
Country [34] 0 0
Poland
State/province [34] 0 0
Gdansk
Country [35] 0 0
Poland
State/province [35] 0 0
Warsaw
Country [36] 0 0
Spain
State/province [36] 0 0
L'Hospitalet de Llobregat
Country [37] 0 0
Spain
State/province [37] 0 0
Madrid
Country [38] 0 0
Spain
State/province [38] 0 0
Santiago de Compostela
Country [39] 0 0
Spain
State/province [39] 0 0
Sevilla
Country [40] 0 0
Spain
State/province [40] 0 0
Valencia
Country [41] 0 0
Switzerland
State/province [41] 0 0
Zuerich
Country [42] 0 0
United Kingdom
State/province [42] 0 0
Glasgow
Country [43] 0 0
United Kingdom
State/province [43] 0 0
Northwood
Country [44] 0 0
United Kingdom
State/province [44] 0 0
Wirral

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
IDEAYA Biosciences
Address
Country

Ethics approval
Ethics application status

Summary
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).
Trial website
https://clinicaltrials.gov/study/NCT05987332
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Darrin Beaupre, MD, Ph.D
Address 0 0
IDEAYA Biosciences
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
IDEAYA Clinical Trials
Address 0 0
Country 0 0
Phone 0 0
1 650-534-3616
Fax 0 0
Email 0 0
IDEAYAClinicalTrials@ideayabio.com
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05987332