Informations générales (source: ClinicalTrials.gov)
A Phase 3 Randomized, Open-Label, Multicenter Clinical Study of CGT9486+Sunitinib vs. Sunitinib in Subjects With Locally Advanced, Unresectable, or Metastatic Gastrointestinal Stromal Tumors
Interventional
Phase 3
Cogent Biosciences, Inc. (Voir sur ClinicalTrials)
avril 2022
janvier 2030
16 juin 2026
This is a Phase 3, open-label, international, multicenter study of CGT9486 in combination
with sunitinib. This is a multi-part study that will enroll approximately 482 patients.
Part 1 consists of two evaluations: 1) confirming the dose of an updated formulation of
CGT9486 to be used in subsequent parts in approximately 20 patients who have received at
least one prior line of therapy for GIST and 2) evaluating the potential for drug-drug
interactions between CGT9486 and sunitinib in approximately 18 patients who have received
at least two prior tyrosine kinase inhibitors (TKIs) for GISTs. The second part of the
study will enroll approximately 388 patients who are intolerant to, or who failed prior
treatment with imatinib only and will compare the efficacy of CGT9486 plus sunitinib to
sunitinib alone with patients being randomized in a 1:1 manner. This study also contains
two substudies: 1) a drug-drug interactions substudy will investigate the potential for
CGT9486 to be a CYP3A4 inducer in approximately 16 patients who have received at least
one prior line of therapy for GIST and 2) a substudy intended to test the efficacy of
bezuclastinib and sunitinib as first-line treatment of GIST in approximately 40
participants with KIT exon 9 mutations and no prior systemic therapy (with the exception
of up to 10 subjects with ongoing imatinib therapy of ≤4 weeks).
Etablissements
| Les établissements d'Île-de-France ayant mis à jour leurs données Origine et niveau de fiabilité des données | |||||
|---|---|---|---|---|---|
| CLCC INSTITUT GUSTAVE ROUSSY | Axel LE CESNE | 08/04/2024 07:25:09 | Contacter | ||
Critères
Tous
1. Histologically confirmed locally advanced, metastatic, and/or unresectable GIST.
Molecular pathology report must be available for Part 2; if molecular pathology
report is unavailable or inadequate, an archival or fresh tumor tissue sample will
be required to evaluate mutational status prior to randomization. (GIST 1L Substudy:
must have documented mutation in KIT Exon 9 with an available molecular pathology
report; archival or fresh tumor tissue sample will be required)
2. Documented disease progression on or intolerance to imatinib (Part 1a, Part 1b, Part
2, DDI Substudy)
3. Subjects must have received the following treatment:
- DDI Substudy/Part 1a: Treatment with ≥1 prior lines of therapy for GIST
- Part 1b: Treatment with ≥2 prior TKI for GISTs
- Part 2: Prior treatment with imatinib only
- GIST 1L Substudy: No prior systemic therapy for GIST including adjuvant
therapy. Exception: up to 10 subjects with ongoing imatinib therapy of ≤4 weeks
4. Have at least 1 measurable lesion according to mRECIST v1.1 (Part1a, Part 1b, Part
2, GIST 1L Substudy)
5. ECOG
- 0 to 2 (Part 1a, Part 1b, Part 2, DDI Substudy)
- 0 to 1 (GIST 1L Substudy)
6. Have clinically acceptable local laboratory screening results (clinical chemistry
and hematology) within certain limits
Key Exclusion Criteria:
1. Known PDGFR driving mutations or known succinate dehydrogenase deficiency (Part 1a,
Part 1b, Part 2, DDI Substudy)
2. Clinically significant cardiac disease
3. Major surgeries (eg, abdominal laparotomy) within 4 weeks of the first dose of study
drug (Part 1a, Part 1b, Part 2, DDI Substudy)
4. Gastrointestinal abnormalities including, but not limited to, significant nausea and
vomiting, malabsorption, external biliary shunt, or significant bowel resection that
would preclude adequate absorption
5. Any active bleeding excluding hemorrhoidal or gum bleeding
6. Seropositive for HIV 1 or 2, or positive for hepatitis B surface antigen or
hepatitis C virus (HCV) antibody.
7. Active, uncontrolled, systemic bacterial, fungal, or viral infections at Screening
8. Received strong CYP3A4 inhibitors or inducers (Part 1a, Part 1b, Part 2, DDI
Substudy)
9. Received sunitinib within 3 weeks (Part 1a, Part 1b, DDI Substudy)