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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04857372




Registration number
NCT04857372
Ethics application status
Date submitted
20/04/2021
Date registered
23/04/2021

Titles & IDs
Public title
A Phase I Study of IAG933 in Patients With Advanced Mesothelioma and Other Solid Tumors
Scientific title
An Open-label, Multi-center, Phase I Study of Oral IAG933 in Adult Patients With Advanced Mesothelioma and Other Solid Tumors
Secondary ID [1] 0 0
CIAG933A12101
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Mesothelioma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Lung - Mesothelioma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - IAG933

Experimental: Group 1 - Malignant pleural mesothelioma

Experimental: Group 2 - NF2 truncating mutations or deletions

Experimental: Group 3 - Solid tumors with functional YAP/TAZ fusions

Experimental: Group 4 - Non-pleural mesothelioma


Treatment: Drugs: IAG933
Capsule
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of patients with adverse events and serious adverse events
Timepoint [1] 0 0
3 years
Primary outcome [2] 0 0
Incidence of dose limiting toxicities during the first treatment cycle (dose escalation only)
Timepoint [2] 0 0
1 year
Primary outcome [3] 0 0
Number of patients with dose interruptions and dose changes
Timepoint [3] 0 0
3 years
Secondary outcome [1] 0 0
Overall response rate (ORR)
Timepoint [1] 0 0
3 years
Secondary outcome [2] 0 0
Disease control rate (DCR)
Timepoint [2] 0 0
3 years
Secondary outcome [3] 0 0
Progression free survival (PFS)
Timepoint [3] 0 0
3 years
Secondary outcome [4] 0 0
Duration of response (DOR)
Timepoint [4] 0 0
3 years
Secondary outcome [5] 0 0
Overall survival (OS) (dose expansion only)
Timepoint [5] 0 0
3 years
Secondary outcome [6] 0 0
Minimum serum concentration (Cmin) (dose escalation only)
Timepoint [6] 0 0
1 year
Secondary outcome [7] 0 0
Maximum serum concentration (Cmax)
Timepoint [7] 0 0
3 years
Secondary outcome [8] 0 0
Time to reach Cmax (Tmax)
Timepoint [8] 0 0
3 years
Secondary outcome [9] 0 0
Area under the curve (AUC)
Timepoint [9] 0 0
3 years
Secondary outcome [10] 0 0
Half life (T1/2) (dose escalation only)
Timepoint [10] 0 0
1 year
Secondary outcome [11] 0 0
Accumulation ratio (Racc) (dose escalation only)
Timepoint [11] 0 0
1 year

Eligibility
Key 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 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:

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.

Group 4: Advanced (unresectable or metastatic) non-pleural mesothelioma patients who have failed available standard therapies for advanced/metastatic disease, are 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, 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
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.

Other protocol-defined inclusion/exclusion criteria may apply.

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
21/10/2021
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
6/10/2025
Actual
Sample size
Target
156
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 0 0
Novartis Investigative Site - Melbourne
Recruitment postcode(s) [1] 0 0
3000 - Melbourne
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Illinois
Country [3] 0 0
United States of America
State/province [3] 0 0
Massachusetts
Country [4] 0 0
United States of America
State/province [4] 0 0
Ohio
Country [5] 0 0
United States of America
State/province [5] 0 0
Texas
Country [6] 0 0
Canada
State/province [6] 0 0
Quebec
Country [7] 0 0
France
State/province [7] 0 0
Villejuif
Country [8] 0 0
Germany
State/province [8] 0 0
Essen
Country [9] 0 0
Italy
State/province [9] 0 0
MI
Country [10] 0 0
Japan
State/province [10] 0 0
Tokyo
Country [11] 0 0
Netherlands
State/province [11] 0 0
Zuid Holland
Country [12] 0 0
Spain
State/province [12] 0 0
Catalunya
Country [13] 0 0
Switzerland
State/province [13] 0 0
Zuerich
Country [14] 0 0
United Kingdom
State/province [14] 0 0
Manchester

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Novartis Pharmaceuticals
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Country 0 0
Phone 0 0
1-888-669-6682
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04857372