Brief Summary
This is a Phase 1/2, multi-center, open-label basket study designed to evaluate the safety and anti-tumor activity of IDE196 in patients with solid tumors harboring GNAQ or GNA11 (GNAQ/11) mutations or PRKC fusions, including metastatic uveal melanomaa type of cancer that develops from melanocytes, which are the cells that produce pigment generally in the skin (but can develop in other areas of the body) (MUM), cutaneous melanoma, colorectalrelating to the colon or rectum in the large bowel/intestine cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs, and other solid tumors.
Phase 1 (dosethe amount of medication taken escalation – monotherapy) will assess safety, tolerability and pharmacokinetics of IDE196 via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.
Phase 1 (dose escalation – binimetib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and binimetinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study.
Phase 1 (dose escalation – crizotinib combination) will assess safety, tolerability and pharmacokinetics of IDE196 and crizotinib via standard dose escalation scheme and determine the recommended Phase 2 dose. Safety and anti-tumor activity will be assessed in the Phase 2 (dose expansion) part of the study. Evaluation of safety and efficacy across multiple doses may be explored in the dose optimization part of the study.
Crizotinib monotherapy with crossover to combination cohort may be assessed for safety and to show the contribution of each study drug to anti-tumor activity.
As of Protocol Amendment 10, Phase 1, Phase 2 dose expansion in IDE196 monotherapy, and Phase 2 dose expansion of IDE196 in combination with binimetinib have been fully enrolled. There were no patients enrolled in the crizotinib monotherapy cohorts.
Intervention / Treatment
- Drug: IDE196
- Drug: Binimetinib
- Drug: Crizotinib
Inclusion Criteria
- Patient must be ≥18 years of age and able to provide written informed consenta process in which a patient receives detailed information about a procedure or treatment, including its potential risks, benefits, and alternatives. The patient then has the opportunity to understand the information and voluntarily agree to the procedure or treatment.
- Diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results of the following:o MUM: Uveal melanoma with histological or cytological confirmed metastatic disease. Metastatic disease may be treatment naïve or have progressed on or after most recent therapy. If the most recent therapy was an immune-oncology agent, PD must be confirmed.
– If a patient is treatment naïve and human leukocyte antigen (HLA)-A*02:01 positive***, documentation is required to provide rationale why treatment with tebentafusp is not the ideal firstline treatment approach or of the patient’s intolerance to tebentafusp.
***To be enrolled in the HLA-A*02:01 positive cohort, HLA status must be documented by test results from a CAP/CLIA-certified laboratory.
- Measurable disease per RECIST v1.1
- Eastern Cooperative Oncologythe study, diagnosis and treatment of cancer Group ≤1 and expected life expectancy of > 3 months
- Adequate organ function at screeningtesting for cancer or conditions that can lead to cancer before symptoms appear, also known as cancer screening
- Adequate contraceptive measures for non-sterilized male and female patients of childbearing potential
Crizotinib Combination Additional Inclusion Criteria:
- Prior chemotherapya cancer treatment that uses drugs to kill or slow the growth of cancer cells, while minimising damage to healthy cells other therapies as applicable or major surgeries must have been completed at least 4 weeks prior to initiation of crizotinib
- Patients with preexisting peripheral neuropathy can be included if it is Gradea description of how abnormal cancer cells and tissue look under a microscope when compared to healthy cells 1 or lower, prior to initiation of crizotinib Biopsy-eligible patients
- Accessible lesion(s) that permit a total of at least two biopsies without unacceptable riskthe possibility that something bad will happen of a significant procedural complication.