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

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ClinicalTrials.gov Identifier: NCT04857372
Recruitment Status : Recruiting
First Posted : April 23, 2021
Last Update Posted : July 5, 2022
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Pharmaceuticals )

Brief Summary:
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 or disease Intervention/treatment Phase
Mesothelioma Drug: IAG933 Phase 1

Detailed Description:
This is a phase I, open-label, multi-center study of IAG933 as a single agent consisting of a dose escalation part, followed by a dose expansion part. The escalation part will characterize the safety and tolerability. After the determination of the recommended dose/maximum tolerated dose, dose expansion will assess the preliminary anti-tumor activity in defined patient populations and further assess the safety and tolerability at RD/MTD.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 156 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Open-label, Multi-center, Phase I Study of Oral IAG933 in Adult Patients With Advanced Mesothelioma and Other Solid Tumors
Actual Study Start Date : October 21, 2021
Estimated Primary Completion Date : September 6, 2024
Estimated Study Completion Date : September 6, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Mesothelioma

Arm Intervention/treatment
Experimental: Group 1
Malignant pleural mesothelioma
Drug: IAG933
Capsule

Experimental: Group 2
NF2 truncating mutations or deletions
Drug: IAG933
Capsule

Experimental: Group 3
Solid tumors with functional YAP/TAZ fusions
Drug: IAG933
Capsule




Primary Outcome Measures :
  1. Number of patients with adverse events and serious adverse events [ Time Frame: 3 years ]
    Safety and tolerability of IAG933

  2. Incidence of dose limiting toxicities during the first treatment cycle (dose escalation only) [ Time Frame: 1 year ]
    Safety, tolerability and the maximum tolerated dose or recommended dose of IAG933

  3. Number of patients with dose interruptions and dose changes [ Time Frame: 3 years ]
    Tolerability of IAG933


Secondary Outcome Measures :
  1. Overall response rate (ORR) [ Time Frame: 3 years ]
    Assess anti-tumor activity as per RECIST v1.1 and mRECIST v1.1 (for the malignant pleural mesothelioma patients)

  2. Disease control rate (DCR) [ Time Frame: 3 years ]
    Assess anti-tumor activity as per RECIST v1.1 and mRECIST v1.1 (for the malignant pleural mesothelioma)

  3. Progression free survival (PFS) [ Time Frame: 3 years ]
    Assess anti-tumor activity as per RECIST v1.1 and mRECIST v1.1 (for the malignant pleural mesothelioma patients)

  4. Duration of response (DOR) [ Time Frame: 3 years ]
    Assess anti-tumor activity as per RECIST v1.1 and mRECIST v1.1 (for the malignant pleural mesothelioma patients)

  5. Overall survival (OS) (dose expansion only) [ Time Frame: 3 years ]
    Assess anti-tumor activity as per RECIST v1.1 and mRECIST v1.1 (for the malignant pleural mesothelioma patients)

  6. Minimum serum concentration (Cmin) (dose escalation only) [ Time Frame: 1 year ]
    Characterize PK of IAG933

  7. Maximum serum concentration (Cmax) [ Time Frame: 3 years ]
    Characterize PK of IAG933

  8. Time to reach Cmax (Tmax) [ Time Frame: 3 years ]
    Characterize PK of IAG933

  9. Area under the curve (AUC) [ Time Frame: 3 years ]
    Characterize PK of IAG933

  10. Half life (T1/2) (dose escalation only) [ Time Frame: 1 year ]
    Characterize PK of IAG933

  11. Accumulation ratio (Racc) (dose escalation only) [ Time Frame: 1 year ]
    Characterize PK of IAG933



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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 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.

  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.

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
  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 outside of the laboratory normal limits:

    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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04857372


Contacts
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Contact: Novartis Pharmaceuticals 1-888-669-6682 novartis.email@novartis.com
Contact: Novartis Pharmaceuticals +41613241111 novartis.email@novartis.com

Locations
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United States, Illinois
University of Chicago Medical Center Recruiting
Chicago, Illinois, United States, 60637-1470
Contact: Cha-Tia Dingle    +1 773 834 0783    cdingle@bsd.uchicago.edu   
Principal Investigator: Hedy Lee Kindler         
United States, Massachusetts
Massachusetts General Hospital Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Ibiayi Dagogo-Jack    617-724-4000    idagogo-jack@partners.org   
Principal Investigator: Ibiayi Dagogo-Jack         
United States, Texas
MD Anderson Cancer Center/University of Texas Recruiting
Houston, Texas, United States, 77030-4009
Contact    713-745-6753      
Principal Investigator: Anne Tsao         
Australia, Victoria
Novartis Investigative Site Recruiting
Melbourne, Victoria, Australia, 3000
Canada, Quebec
Novartis Investigative Site Recruiting
Montreal, Quebec, Canada, H2W 1T8
Germany
Novartis Investigative Site Recruiting
Essen, Germany, 45147
Italy
Novartis Investigative Site Recruiting
Rozzano, MI, Italy, 20089
Japan
Novartis Investigative Site Recruiting
Chuo ku, Tokyo, Japan, 104 0045
Spain
Novartis Investigative Site Recruiting
Barcelona, Catalunya, Spain, 08035
United Kingdom
Novartis Investigative Site Recruiting
Manchester, United Kingdom, M20 4BX
Sponsors and Collaborators
Novartis Pharmaceuticals
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Responsible Party: Novartis Pharmaceuticals
ClinicalTrials.gov Identifier: NCT04857372    
Other Study ID Numbers: CIAG933A12101
First Posted: April 23, 2021    Key Record Dates
Last Update Posted: July 5, 2022
Last Verified: June 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Novartis ( Novartis Pharmaceuticals ):
Mesothelioma
IAG933
NF2 mutated tumors
LATS1/LATS2 mutated tumors
YAP/TAZ
Additional relevant MeSH terms:
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Mesothelioma
Mesothelioma, Malignant
Adenoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Mesothelial
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Pleural Neoplasms
Lung Diseases
Respiratory Tract Diseases