CLINICAL TRIAL / NCT04857372
A Phase I Study of IAG933 in Patients With Advanced Mesothelioma and Other Solid Tumors
- Interventional
- Recruiting
- NCT04857372
Contact Information
An Open-label, Multi-center, Phase I Study of Oral IAG933 in Adult Patients With Advanced Mesothelioma and Other Solid Tumors
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.
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.
Gender
All
Age Group
18 Years and up
Accepting Healthy Volunteers
No
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.
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.