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

NCT04857372 | Active Not Recruiting Phase 1 FDA Drug

• 1 other identifier: CIAG933A12101
• Study Type: interventional
• Target: 137
• Locations: 11 countries
• Sites: 16

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.

Conditions

Mesothelioma

Keywords

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

Outcome Measures

Primary Outcomes (3)

• Number of patients with adverse events and serious adverse events

  Safety and tolerability of IAG933

  3 years

• Incidence of dose limiting toxicities during the first treatment cycle (dose escalation only)

  Safety, tolerability and the maximum tolerated dose or recommended dose of IAG933

  1 year

• Number of patients with dose interruptions and dose changes

  Tolerability of IAG933

  3 years

Secondary Outcomes (11)

• Overall response rate (ORR)

  3 years

• Disease control rate (DCR)

  3 years

• Progression free survival (PFS)

  3 years

• Duration of response (DOR)

  3 years

• Overall survival (OS) (dose expansion only)

  3 years

Study Arms (4)

Group 1

EXPERIMENTAL

Malignant pleural mesothelioma

Drug: IAG933

Group 2

EXPERIMENTAL

NF2 truncating mutations or deletions

Drug: IAG933

Group 3

EXPERIMENTAL

Solid tumors with functional YAP/TAZ fusions

Drug: IAG933

Group 4

EXPERIMENTAL

Non-pleural mesothelioma

Drug: IAG933

Interventions

IAG933 DRUG

Capsule

Group 1; Group 2; Group 3; Group 4

Eligibility Criteria

• Age: 18 Years - 120 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.
• 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.
• 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. An archival tumor sample may be used at screening. During the dose expansion part of the study, a decision may be made to stop the collection of on-treatment biopsies.

You may not qualify if:

• 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 biological therapy (including monoclonal antibodies) or continuous or intermittent small molecule therapeutics or any other investigational agent.
• ≤3 weeks for treatment with cytotoxic agents or ≤ 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
• Prior treatment with TEAD inhibitor at any time
• 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 \> Common Terminology Criteria for Adverse Events (CTCAE) grade 1:
• Potassium
• Magnesium

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (16)

University of California LA

Los Angeles, California, 90095, United States

Location

Uni of Chi Medi Ctr Hema and Onco

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Cleveland Clinic Foundation

Cleveland, Ohio, 44195, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030 4009, United States

Location

Novartis Investigative Site

Melbourne, Victoria, 3000, Australia

Location

Novartis Investigative Site

Montreal, Quebec, H2W 1T8, Canada

Location

Novartis Investigative Site

Villejuif, 94800, France

Location

Novartis Investigative Site

Essen, 45147, Germany

Location

Novartis Investigative Site

Milan, MI, 20133, Italy

Location

Novartis Investigative Site

Rozzano, MI, 20089, Italy

Location

Novartis Investigative Site

Chuo Ku, Tokyo, 104 0045, Japan

Location

Novartis Investigative Site

Rotterdam, South Holland, 3015 GD, Netherlands

Location

Novartis Investigative Site

Barcelona, Catalonia, 08035, Spain

Location

Novartis Investigative Site

Zurich, 8091, Switzerland

Location

Novartis Investigative Site

Manchester, M20 2BX, United Kingdom

Location

MeSH Terms

Conditions

Mesothelioma

Condition Hierarchy (Ancestors)

Adenoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Mesothelial

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 20, 2021
• First Posted: April 23, 2021
• Study Start: October 21, 2021
• Primary Completion (Estimated): September 4, 2026
• Study Completion (Estimated): September 4, 2026
• Last Updated: September 19, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

IT (2); AU (1); CH (1); DE (1); FR (1); JP (1); US (5); GB (1); CA (1); NL (1); ES (1)