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

Ideaya Biosciences

Status and phase: Enrolling; Phase 3; Phase 2

Conditions: Metastatic Uveal Melanoma

Treatments: Drug: IDE196; Drug: Nivolumab; Drug: Dacarbazine; Drug: Pembrolizumab; Drug: Crizotinib; Drug: Ipilimumab

Study type: Interventional

Funder types: Industry

Identifiers

NCT05987332

IDE196-002

Details and patient eligibility

About

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).

Full 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.

Enrollment: 420 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No 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 or regional or liver-directed therapy. Ablations or surgical resection of oligometastatic disease, and 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
• High risk of syncope
• Known AIDS related illness or active 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
• History of stroke within the last 6 months of the first dose of study drug
• 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, including institutionalization on the basis of an official or court order

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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420 participants in 3 patient groups

Phase 2a Dose Optimization of IDE196 + crizotinib

Experimental group

Description:

Multiple doses of IDE196 will be tested in combination with fixed dose of crizotinib to identify the optimal combination dose.

Treatment:

Drug: Crizotinib

Drug: IDE196

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

Experimental group

Description:

Chosen combination dose of IDE196 + crizotinib will be tested in additional participants.

Treatment:

Drug: Crizotinib

Drug: IDE196

Phase 2a / 2b / 3 Comparator Arm

Active Comparator group

Description:

Participants will receive investigator's choice of Pembrolizumab, Ipilimumab + Nivolumab, or Dacarbazine.

Treatment:

Drug: Ipilimumab

Drug: Pembrolizumab

Drug: Dacarbazine

Drug: Nivolumab