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JOURNAL ONKOLOGIE – STUDIE

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

Rekrutierend

NCT-Nummer:
NCT04857372

Studienbeginn:
Oktober 2021

Letztes Update:
12.03.2024

Wirkstoff:
IAG933

Indikation (Clinical Trials):
Mesothelioma, Mesothelioma, Malignant

Geschlecht:
Alle

Altersgruppe:
Erwachsene (18+)

Phase:
Phase 1

Sponsor:
Novartis Pharmaceuticals

Collaborator:
-

Kontakt

Studienlocations
(3 von 14)

Novartis Investigative Site
45147 Essen
(Nordrhein-Westfalen)
GermanyRekrutierend» Google-Maps
Uni of Chi Medi Ctr Hema and Onco Main Centre
60637 Chicago
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Owen Mitchell
Phone: +1 773 834 0783
E-Mail: owenmitchell@medicine.bsd.uchicago.edu» Ansprechpartner anzeigen
Massachusetts General Hospital Massachusetts General Hospital
02114 Boston
United StatesRekrutierend» Google-Maps
Ansprechpartner:
Ibiayi Dagogo-Jack
Phone: 617-724-4000
E-Mail: idagogo-jack@partners.org» Ansprechpartner anzeigen
Novartis Investigative Site
3000 Melbourne
AustraliaRekrutierend» Google-Maps
Novartis Investigative Site
H2W 1T8 Montreal
CanadaRekrutierend» Google-Maps
Novartis Investigative Site
94800 Villejuif
FranceRekrutierend» Google-Maps
Novartis Investigative Site
104 0045 Chuo ku
JapanRekrutierend» Google-Maps
Novartis Investigative Site
3015 GD Rotterdam
NetherlandsRekrutierend» Google-Maps
Novartis Investigative Site
8091 Zuerich
SwitzerlandRekrutierend» Google-Maps
Novartis Investigative Site
M20 4BX Manchester
United KingdomRekrutierend» Google-Maps
Alle anzeigen

Studien-Informationen

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.

Ein-/Ausschlusskriterien

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.

Studien-Rationale

Primary outcome:

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:

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), and RANO (for patients with primary brain/CNS tumors)

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), and RANO (for patients with primary brain/CNS tumors)

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), and RANO (for patients with primary brain/CNS tumors)

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), and RANO (for patients with primary brain/CNS tumors)

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), and RANO (for patients with primary brain/CNS tumors)

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

Studien-Arme

  • 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

Geprüfte Regime

  • IAG933:
    Capsule

Quelle: ClinicalTrials.gov


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