IDE196 (DAROVASERTIB) IN COMBINATION WITH CRIZOTINIB VERSUS INVESTIGATOR’S CHOICE OF TREATMENT AS FIRST-LINE THERAPY IN HLA-A2 NEGATIVE METASTATIC UVEAL MELANOMA
- Conditions
- HLA-A2 negative metastatic uveal melanomaMedDRA version: 21.1Level: PTClassification code: 10081431Term: Uveal melanoma Class: 100000004864Therapeutic area: Diseases [C] - Eye Diseases [C11]Therapeutic area: Diseases [C] - Neoplasms [C04]Therapeutic area: Phenomena and Processes [G] - Ocular Physiological Phenomena [G14]
- Registration Number
- CTIS2023-506686-66-00
- Lead Sponsor
- Ideaya Biosciences Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- All
- Target Recruitment
- 251
1. Must be at least 18 years of age., 10. Has a life expectancy of =3 months., 11. Has adequate organ function (screening assessment must be obtained within 14 days of the first dose of study treatment): • Absolute neutrophil count =1500/mm3 without the use of hematopoietic growth factors • Platelet count =100,000/mm3 (must be at least 2 weeks post-platelet transfusion and not receiving platelet-stimulating agents) • Hemoglobin =9.0 g/dL (must be at least 2 weeks post-red blood cell transfusion) • Total and direct bilirubin =1.5 x the upper limit of normal (ULN). For participants with documented Gilbert’s disease, total bilirubin =3.0 mg/dL is allowed • Aspartate transferase (AST) and alanine transferase (ALT) =3 x ULN in the absence of documented liver metastases; =5 x ULN in the presence of liver metastases • Serum albumin =3.0 g/dL • Creatinine clearance =45 mL/min by Cockcroft-Gault equation (see Appendix 1, Section 14.1) • Prothrombin time/International Normalized Ratio (INR) or partial thromboplastin time test results at screening =1.5 x ULN (this applies only to participants who do not receive therapeutic anticoagulation; participants receiving therapeutic anticoagulation should be on a stable dose for at least 2 weeks prior to the first dose of study drug), 12. Women of childbearing potential who are sexually active with a non-sterilized male partner, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception during study treatment (see Appendix 5, Section 14.5), and must agree to continue using such precautions for 6 months after the final dose of study treatment; cessation of birth control after this point should be discussed with a responsible physician. Highly effective methods of contraception are described in Appendix 5, Section 14.5., 13. Male participants must be surgically sterile or must agree to use double barrier contraception methods from enrollment through treatment and for 6 months following administration of the last dose of study treatment., 2. Is able to provide written, informed consent before initiation of any study related-procedures, and is able, in the opinion of the Investigator, to comply with all the requirements of the study., 3. Has histological or cytological confirmed UM with metastatic disease, 4. HLA-A*02:01 negative, 5. Must meet the following criteria related to prior treatment: • No prior systemic therapy in the metastatic or advanced setting including chemotherapy, immunotherapy, or targeted therapy • No prior regional, liver-directed therapy including chemotherapy, radiotherapy, or embolization • Prior ablations or surgical resection of oligometastatic disease are allowed • Prior neoadjuvant or adjuvant therapy is allowed provided administered in the curative setting in participants with localized disease and a minimum of 4 weeks (28 days) has elapsed since the end of neoadjuvant/adjuvant treatment and the start of study treatment o Participants who have received a combination of anti-PD(L)1 plus anti-CTLA-4 as prior neoadjuvant/adjuvant treatment should not receive ipilimumab + nivolumab as investigator’s choice therapy o Participants who have received an anti-PD(L)1 agent as prior neoadjuvant/adjuvant treatment should not receive pembrolizumab as investigator’s choice therapy o Participants who have received a dacarbazine-containing regimen as prior neoadjuvant/adjuvant treatment should not receive dacarbazine as investigator’s ch
1. Has received previous treatment with a PKC inhibitor (including prior treatment with IDE196), an inhibitor directly targeting MET, or an inhibitor directly targeting GNAQ/11., 10. Active hepatitis B virus (HBV) or hepatitis C virus (HCV) infection per institutional protocol. Testing for HBV or HCV status is not necessary unless clinically indicated or the participant has a history of HBV or HCV infection. NOTE: participants with suspected hepatitis should be discussed with the Sponsor Medical Monitor., 11. Major surgery within 2 weeks of the first dose of study drug (minimally invasive procedures such as bronchoscopy, tumor biopsy, insertion of a central venous access device, and insertion of a feeding tube are not considered major surgery and are not exclusionary)., 12. Radiotherapy within 2 weeks of the first dose of study drug, with the exception of palliative radiotherapy to a limited field, such as for the treatment of bone pain or a focally painful tumor mass., 13. Use of hematopoietic colony-stimulating factors (CSF) (eg, granulocyte [G]-CSF, granulocyte-macrophage [GM]-CSF, macrophage [M]-CSF) within2 weeks prior to start of study drug. An erythroid-stimulating agent is allowed as long as it was initiated at least 2 weeks prior to the first dose of study treatment and the participant is not red blood cell transfusion dependent., 14. Receives treatment with medications that cannot be discontinued prior to study entry and that are considered to be any of the following (see Table 19): • Known risk for QT prolongation, except for the specific use of oral 5-HT3 Receptor Antagonists (eg., granisetron, ondansetron or dolansetron) for the management of nausea and vomiting (note: intravenous formulations are prohibited) • Known to be strong inducers or inhibitors of cytochrome P (CYP)3A4/5 • Known to be substrates of CYP3A4/5 with a narrow therapeutic index • Known to be sensitive substrates to P-gp, BCRP, OAT3, MATE-1 and MATE-2K, 15. Females who are pregnant or breastfeeding, 16. History of severe hypersensitivity reactions (eg, anaphylaxis) to other biologic drugs or monoclonal antibodies., 17. Impaired cardiac function or clinically significant cardiac diseases, including any of the following: •A history or presence of ventricular tachyarrhythmia •Presence of unstable atrial fibrillation (ventricular response >100 beats per minute [bpm]); participants with stable atrial fibrillation are eligible, provided they do not meet any of the other cardiac exclusion criteria •Has had angina pectoris or acute myocardial infarction =6 months prior to study treatment •Has congestive heart failure requiring treatment. For New York Heart Association Class 1, inclusion can be considered with discussion and agreement with the Medical Monitor •Has other clinically significant heart disease (eg, uncontrolled arrhythmia or hypertension; history of labile hypertension or poor compliance with an antihypertensive regimen, symptomatic bradycardia) •Has a drug eluting stent for cardiovascular purposes placed =2 months prior to study treatment •Corrected QT interval using Fridericia’s method (QTcF) (see Appendix 2, Section 14.2): -QTcF >470 msec on baseline electrocardiogram (ECG) (mean of baseline values). If electrolytes are abnormal, they may be corrected, and baseline ECGs should be repeated. In addition, participants with asymptomatic persistent heart rate <55 bpm must be discussed with the Medical Monitor for inclusion NOTE: for participants
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method