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

a study on Ocular Melanoma Skin Cancer/Melanoma

Summary

Eligibility
for people ages 18 years and up (full criteria)
Location
at UCLA UCSD UCSF
Dates
study started
completion around

Description

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).

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)

Details

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.

Keywords

Metastatic Uveal Melanoma, IDE196, Darovasertib, Protein Kinase C, Melanoma, Ocular Oncology, Ophthalmology, Crizotinib, Ocular melanoma, Uveal Neoplasms, Pembrolizumab, Nivolumab, Ipilimumab, Dacarbazine

Eligibility

You can join if…

Open to people ages 18 years and up

  • 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

You CAN'T join if...

  • 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

Locations

  • UCLA Medical Center accepting new patients
    Los Angeles California 90024 United States
  • University of California San Francisco accepting new patients
    San Francisco California 94143 United States
  • The Angeles Clinic and Research Institute accepting new patients
    Los Angeles California 90025 United States
  • California Pacific Medical Center (CPMC) accepting new patients
    San Francisco California 94115 United States
  • Moores Cancer Center not yet accepting patients
    La Jolla California 92093 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
IDEAYA Biosciences
ID
NCT05987332
Phase
Phase 2/3 research study
Study Type
Interventional
Participants
Expecting 380 study participants
Last Updated