An open-label, multi-center, Phase I study of oral IAG933 in adult patients with advanced Mesothelioma and other solid tumors

Recruiting

• Conditions: asbestos-cancer; mesothelioma; 10027412

• Registration Number: NL-OMON54125
• Lead Sponsor: ovartis

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Last Update Posted: 15 April 2024

Recruitment & Eligibility

• Status: Recruiting
• Sex: Not specified
• Target Recruitment: 10

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

1. Treatment with any of the following anti-cancer therapies prior to the first
dose of study treatment within the stated timeframes:
a. <= 4 weeks for thoracic radiotherapy to lung fields or limited field
radiation for palliation within <= 2 weeks prior to the first dose of study
treatment. An exception to this exists for patients who have received
palliative radiotherapy to bone, who must have recovered from
radiotherapy-related toxicities but for whom a 2-week washout period is not
required.
b. <= 4 weeks or <= 5 half-lives (whichever is shorter) for chemotherapy or
biological therapy (including monoclonal antibodies) or continuous or
intermittent small molecule therapeutics or any other investigational agent.
c. <= 6 weeks for cytotoxic agents with risk of major delayed toxicities, such
as nitrosoureas and mitomycin C.
d. <= 4 weeks for immuno-oncologic therapy, such as CTLA4, PD-1, or PD-L1
antagonists
e. Prior treatment with TEAD inhibitor at any time
2. For mesothelioma patients: use of non-invasive antineoplastic therapy (e.g.,
tumor treating fields, brand name Optune LuaTM) within 2 weeks of the tumor
assessment at screening.
3. Malignant disease, other than that being treated in this study. Exceptions
to this exclusion include the following: malignancies that were treated
curatively and have not recurred within 2 years prior to study entry;
completely resected basal cell and squamous cell skin cancers; any malignancy
considered to be indolent and that has never required therapy; and completely
resected carcinoma in situ of any type.
4. Presence of symptomatic CNS metastases, or CNS tumors or metastases that
require local CNS-directed therapy (such as radiotherapy within 3 months of
tumor assessment at screening or surgery), or increasing doses of
corticosteroids 2 weeks prior to study entry.
Patients with treated symptomatic brain tumors should be neurologically stable
(for 4 weeks post-treatment and prior to study entry) and at a dose of <= 10 mg
per day prednisone or equivalent for at least 2 weeks before administration of
any study treatment
5. Patients who have undergone major surgery <= 4 weeks prior to first dose of
study treatment
6. History of allogeneic bone marrow or solid organ transplant.
7. Insufficient renal function at Screening:
a. Serum creatinine > 1.5 x ULN
b. Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73m2 (calculated
using the Cockcroft-Gault formula, or the CKD-EPI Creatinine-Cystatin C formula
as listed in Appendix 7).
c. Urine protein-creatinine ratio > 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) < 50% as determined by
Cardiovascular magnetic resonance imaging (cardiac magnetic resonance imaging
(MRI)) or trans-thoracic echocardiography (TTE).
d. Resting QTcF >=450 msec (male) or >=460 msec (female) at screening, or QTc not
assessable
e. Resting heart rate (physi

Study & Design

• Study Type: Interventional
• Study Design: Not specified