A Phase I Study of IAG933 in Patients With Advanced Mesothelioma and Other Solid Tumors

An Open-label, Multi-center, Phase I Study of Oral IAG933 in Adult Patients With Advanced Mesothelioma and Other Solid Tumors

ClinicalTrials.gov Identifier: NCT04857372

Novartis Reference Number: CIAG933A12101

Last Update: May 12, 2022

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All compounds are either investigational or being studied for (a) new use(s). Efficacy and safety have not been established. There is no guarantee that they will become commercially available for the use(s) under investigation. 

Study Description

The purpose of this study is to characterize the safety and tolerability of IAG933 in patients with mesothelioma, NF2/LATS1/LATS2 mutated tumors and tumors with functional YAP/TAZ fusions and to identify the maximum tolerated dose and/or recommended dose.

Condition 
Mesothelioma
Phase 
Phase 1
Overall status 
Recruiting
Start date 
Oct 21, 2021
Completion date 
Sep 06, 2024
Gender 
All
Age(s)
18 Years and older (Adult, Older Adult)

Interventions

Drug
IAG933
Capsule

Eligibility Criteria

Inclusion Criteria:

Signed informed consent must be obtained prior to participation in the study.
Male or female patients must be ≥ 18 years of age.
Dose escalation part: 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. 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.

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. 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. 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.

Presence of at least one measurable lesion according to mRECIST v1.1 for mesothelioma patients, RECIST v1.1 for patients with other solid tumors, or RANO for patients with primary brain tumors.
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.

Exclusion Criteria:

Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:

≤ 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.
≤ 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.
≤ 6 weeks for cytotoxic agents with risk of major delayed toxicities, such as nitrosoureas and mitomycin C.
≤ 4 weeks for immuno-oncologic therapy, such as CTLA4, PD-1, or PD-L1 antagonists
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.
Malignant disease, other than that being treated in this study.
Insufficient renal function at Screening.
Clinically significant cardiac disease or risk factors at screening
Insufficient bone marrow function at screening.
Insufficient hepatic function at screening.

Patients who have the following laboratory values outside of the laboratory normal limits:

Potassium
Magnesium
Total calcium (corrected for low serum albumin)
Known active COVID-19 infection.
Pregnant or nursing (lactating) women,
Japan only: patients with a history of drug- and/or non-drug-induced interstitial lung disease (ILD) ≥ Grade 2.

Other protocol-defined inclusion/exclusion criteria may apply.

Study Locations

United States
University of Chicago Medical Center
Recruiting
Chicago, 60637-1470 - Illinois
Contact: (+1 773 834 0783) Hedy Lee Kindler
United States
Massachusetts General Hospital Massachusetts General Hospital
Recruiting
Boston, 02114 - Massachusetts
Contact: Ibiayi Dagogo-Jack (617-724-4000) - [email protected] - Ibiayi Dagogo-Jack
United States
MD Anderson Cancer Center/University of Texas
Recruiting
Houston, 77030-4009 - Texas
Contact: (713-745-6753) Anne Tsao
United States
Australia
Novartis Investigative Site
Recruiting
Melbourne, 3000
Victoria
Australia
Germany
Novartis Investigative Site
Recruiting
Essen, 45147
-
Germany
Italy
Novartis Investigative Site
Recruiting
Rozzano, 20089
MI
Italy
Japan
Novartis Investigative Site
Recruiting
Chuo ku, 104 0045
Tokyo
Japan
Spain
Novartis Investigative Site
Recruiting
Barcelona, 08035
Catalunya
Spain
United Kingdom
Novartis Investigative Site
Recruiting
Manchester, M20 4BX
-
United Kingdom

Contacts

Name: 
Novartis Pharmaceuticals
Phone: 
Name: 
Novartis Pharmaceuticals
Phone: 

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Call 1-888-669-6682 or email [email protected]