asbestos-cancer mesothelioma
Conditions
Interventions
For this study, *investigational drug* and *study treatment* refer to IAG933.
The investigational drugs used in this study are listed in Table 6-1 in the
protocol. Additional drug strengths may beco
Sponsors
Novartis
Eligibility
Age
18 Years to 99 Years
Inclusion criteria
Inclusion criteria: 1.Signed informed consent must be obtained prior to participation in the study. 2. Male or female patients must be >= 18 years of age 3. (dose escalation) Patients with histologically or cytologically confirmed diagnosis of advanced (unresectable or metastatic) mesothelioma or other solid tumors. Patients with solid tumors other than mesothelioma must have local available data for loss-of-function NF2/LATS1/LATS2 genetic alterations (truncating mutation or gene deletion; LATS1/LATS2 mutations will only be included in the dose escalation part), or functional YAP/TAZ fusions (see Appendix 4 for requirements for molecular alterations ). Patients with malignant EHE can be enrolled with only histological confirmation of the disease. Patients must have failed available standard therapies, be intolerant of or ineligible for standard therapy, or for whom no standard therapy exists. 4. Dose expansion part: the following patients will be enrolled into 3 different treatment groups: Group 1: Advanced (unresectable or metastatic) MPM patients who have failed available standard therapies for advanced/metastatic disease, be intolerant or ineligible to receive such therapy, or for whom no standard therapy exists. Group 2: Advanced (unresectable or metastatic) solid tumor patients with available local data for NF2 truncating mutation or deletions (refer to Appendix 4 for more details). Patient must have failed available standard therapies, be intolerant or ineligible to receive such therapy, or for whom no standard therapy exists. Group 3: Advanced (unresectable or metastatic) solid tumor patients with available local data for functional YAP/TAZ fusions (refer to Appendix 4 for more details). EHE patients can be included with only histological confirmation of the disease. Patient must have failed available standard therapies, be intolerant or ineligible to receive such therapy, or for whom no standard therapy exists. 5. Presence of at least one measurable lesion according to mRECIST v1.1 (for mesothelioma patients, refer to Appendix 2), RECIST v1.1 (for patients with other solid tumors, refer to Appendix 1), or RANO (for patients with primary brain tumors, refer to Appendix 3). 6. Patient must have a site of disease amenable to biopsy and be a candidate for tumor biopsy according to the treating institution*s guidelines. Patient must be willing to undergo a new tumor biopsy at screening/baseline, and again during therapy on this study. Archival tissue obtained within 3 months and after last systemic treatment may be used at screening. Exceptions may be considered after documented discussion with Novartis. 7. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
Exclusion criteria
Exclusion criteria: 1. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes: a. 1.5 x ULN b. Estimated glomerular filtration rate (eGFR) 0.5 g/g (56.5 mg/mmol) 8. Clinically significant cardiac disease or risk factors at screening, including any of the following: a. Clinically significant and/or uncontrolled heart disease, including coronary artery disease, uncontrolled hypertension, clinically significant arrhythmia, and congestive heart failure (NYHA grade >= 2). b. Acute myocardial infarction or unstable angina pectoris within 6 months prior to study entry. c. Left ventricular ejection fraction (LVEF) =450 msec (male) or >=460 msec (female) at screening, or QTc not assessable e. Resting heart rate (physi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Safety: Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs), including clinically significant changes in laboratory parameters, vital signs, and ECGs. Incidence and nature of dose limiting toxicities (DLTs) during the first cycle of dosing Tolerability: Dose interruptions, reductions and dose intensity See also section 2 of the protocol. | — |
Secondary
| Measure | Time frame |
|---|---|
| Overall Response Rate (ORR), disease control rate (DCR), progression-free survival (PFS), duration of response (DOR) as per RECIST v1.1* Plasma concentration vs. time profiles and derived PK parameters for IAG933 such as Cmax, Tmax, Cmin, AUC, T1/2, Racc ORR, DCR, PFS, DOR as per RECIST v1.1* OS | — |
Countries
Netherlands
Outcome results
None listed