RECRUITING

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

Conditions

Mesothelioma IAG933 NF2 mutated tumors LATS1/LATS2 mutated tumors YAP/TAZ

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

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.

Official Title

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

Quick Facts

Study Start:2021-10-21

Study Completion:2026-01-12

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:RECRUITING

Study ID

NCT04857372

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion 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 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. 4. Dose expansion part: the following patients will be enrolled into 3 different treatment groups: 5. 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. 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.	1. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes: 1. ≤ 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. 2. ≤ 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. 3. ≤ 6 weeks for cytotoxic agents with risk of major delayed toxicities, such as nitrosoureas and mitomycin C. 4. ≤ 4 weeks for immuno-oncologic therapy, such as CTLA4, PD-1, or PD-L1 antagonists 5. 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. 4. Insufficient renal function at Screening. 5. Clinically significant cardiac disease or risk factors at screening 6. Insufficient bone marrow function at screening. 7. Insufficient hepatic function at screening. 8. Patients who have the following laboratory values \> Common Terminology Criteria for Adverse Events (CTCAE) grade 1: 1. Potassium 2. Magnesium 3. Total calcium (corrected for low serum albumin) 9. Known active COVID-19 infection. 10. Pregnant or nursing (lactating) women, 11. Japan only: patients with a history of drug- and/or non-drug-induced interstitial lung disease (ILD) ≥ Grade 2.

Inclusion Criteria

Exclusion 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 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.
4. Dose expansion part: the following patients will be enrolled into 3 different treatment groups:
5. 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.
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.

1. Treatment with any of the following anti-cancer therapies prior to the first dose of study treatment within the stated timeframes:
1. ≤ 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.
2. ≤ 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.
3. ≤ 6 weeks for cytotoxic agents with risk of major delayed toxicities, such as nitrosoureas and mitomycin C.
4. ≤ 4 weeks for immuno-oncologic therapy, such as CTLA4, PD-1, or PD-L1 antagonists
5. 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.
4. Insufficient renal function at Screening.
5. Clinically significant cardiac disease or risk factors at screening
6. Insufficient bone marrow function at screening.
7. Insufficient hepatic function at screening.
8. Patients who have the following laboratory values \> Common Terminology Criteria for Adverse Events (CTCAE) grade 1:
1. Potassium
2. Magnesium
3. Total calcium (corrected for low serum albumin)
9. Known active COVID-19 infection.
10. Pregnant or nursing (lactating) women,
11. Japan only: patients with a history of drug- and/or non-drug-induced interstitial lung disease (ILD) ≥ Grade 2.

Contacts and Locations

Study Contact

Novartis Pharmaceuticals

CONTACT

1-888-669-6682

novartis.email@novartis.com

Novartis Pharmaceuticals

CONTACT

+41613241111

novartis.email@novartis.com

Study Locations (Sites)

University Of California LA Santa Monica Location

Los Angeles, California, 90095

United States

Uni of Chi Medi Ctr Hema and Onco Main Centre

Chicago, Illinois, 60637

United States

Sidney Kimmel CCC At JH .

Baltimore, Maryland, 21231

United States

Massachusetts General Hospital Massachusetts General Hospital

Boston, Massachusetts, 02114

United States

Cleveland Clinic Foundation .

Cleveland, Ohio, 44195

United States

MD Anderson Cancer Center Potential Gynecologic Oncology

Houston, Texas, 77030 4009

United States

Collaborators and Investigators

Sponsor: Novartis Pharmaceuticals

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2021-10-21

Study Completion Date2026-01-12

Study Record Updates

Study Start Date2021-10-21

Study Completion Date2026-01-12

Terms related to this study

Keywords Provided by Researchers

Mesothelioma
IAG933
NF2 mutated tumors
LATS1/LATS2 mutated tumors
YAP/TAZ

Additional Relevant MeSH Terms

Mesothelioma