An open-label, multicenter Phase I study of oral IAG933 in adult patients with advanced mesothelioma or other solid tumors

Australia, Canada, France, Germany, Italy, Japan, Netherlands, Spain, Switzerland, United Kingdom, United States (ICTRP)

Identifiant de l'essai ICTRP
NCT04857372 (ICTRP)

Titre officiel (approuvé par le comité d'éthique)
An open-label, multi-center, Phase I study of oral IAG933 in adult patients with advanced Mesothelioma and other solid tumors (BASEC)

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

Titre public
A Phase I Study of IAG933 in Patients With Advanced Mesothelioma and Other Solid Tumors (ICTRP)

Maladie en cours d'investigation
Mesothelioma (ICTRP)

Intervention étudiée
Drug: IAG933 (ICTRP)

Type d'essai
Interventional (ICTRP)

Plan de l'étude
Allocation: Non-Randomized. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Critères d'inclusion/exclusion
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. 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.

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 biological therapy
(including monoclonal antibodies) or continuous or intermittent small molecule
therapeutics or any other investigational agent.

3. =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. = 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. (ICTRP)

non disponible

Critères d'évaluation principaux et secondaires
Number of patients with adverse events and serious adverse events;Incidence of dose limiting toxicities during the first treatment cycle (dose escalation only);Number of patients with dose interruptions and dose changes (ICTRP)

Overall response rate (ORR);Disease control rate (DCR);Progression free survival (PFS);Duration of response (DOR);Overall survival (OS) (dose expansion only);Minimum serum concentration (Cmin) (dose escalation only);Maximum serum concentration (Cmax);Time to reach Cmax (Tmax);Area under the curve (AUC);Half life (T1/2) (dose escalation only);Accumulation ratio (Racc) (dose escalation only) (ICTRP)

Date d'enregistrement
non disponible

Inclusion du premier participant
non disponible

Sponsors secondaires
non disponible

Contacts supplémentaires
Novartis Pharmaceuticals, novartis.email@novartis.com, 1-888-669-6682 (ICTRP)

ID secondaires
CIAG933A12101 (ICTRP)

Résultats-Données individuelles des participants
non disponible

Informations complémentaires sur l'essai
https://clinicaltrials.gov/ct2/show/NCT04857372 (ICTRP)