A Phase Ib/II Study of GFH276 in Combination With Chemotherapy (± Bevacizumab) or Cetuximab in Patients With RAS-mutant Metastatic Colorectal Cancer (A Phase Ib/II)
An Open-label, Multicenter, Phase Ib/II Study to Evaluate the Safety/Tolerability, Efficacy, and Pharmacokinetic Characteristics of GFH276 in Combination With Chemotherapy (+/- Bevacizumab) or Cetuximab in Patients With RAS-mutant Metastatic Colorectal Cancer
This is a Phase Ib/II study to explore the safety/tolerability, efficacy, and pharmacokinetic (PK) characteristics of GFH276 in combination with chemotherapy (+/- bevacizumab) or cetuximab in patients with RAS-mutant metastatic colorectal cancer (mCRC).
Aperçu de l'étude
Statut
Les conditions
Intervention / Traitement
Description détaillée
This is a multicenter, open-label, Phase Ib/II study to evaluate the safety/tolerability, efficacy, and PK characteristics of GFH276 in combination with chemotherapy (+/- bevacizumab) or cetuximab in patients with RAS-mutant mCRC. The study includes a Phase Ib dose-escalation part and a Phase II part.
Cohort 1 is an open-label, multicenter study to evaluate GFH276 in combination with FOLFIRI±bev in patients with RAS-mutant metastatic colorectal cancer.
Cohort 2 is an open-label, multicenter study to evaluate GFH276 in combination with mFOLFOX6±bev in patients with RAS-mutant metastatic colorectal cancer.
Cohort 3 is an open-label, multicenter study to evaluate GFH276 in combination with Cetuximab in patients with RAS-mutant metastatic colorectal cancer.
Cohort A is an open-label, multicenter study to evaluate GFH276 in combination with FOLFIRI or mFOLFOX6±bev in patients with RAS-mutant metastatic colorectal cancer.
Cohort B is an open-label, multicenter study to evaluate GFH276 in combination with Cetuximab in patients with RAS-mutant metastatic colorectal cancer.
Cohort C is an open-label, multicenter study to evaluate FOLFIRI or mFOLFOX6+bev in patients with RAS-mutant metastatic colorectal cancer.
Type d'étude
Inscription (Estimé)
Phase
- Phase 2
- La phase 1
Contacts et emplacements
Coordonnées de l'étude
- Nom: yuting peng, PM
- Numéro de téléphone: 13730813620
- E-mail: ytpeng@genfleet.com
Critères de participation
Critère d'éligibilité
Âges éligibles pour étudier
Accepte les volontaires sains
Sexes éligibles pour l'étude
La description
Inclusion Criteria:
- Subjects must voluntarily agree to participate in the trial and sign a written informed consent form.
- Male or female ≥ 18 years old and ≤75 years old.
- Histologically confirmed metastatic colorectal cancer (mCRC)
- Participants must have experienced disease progression or recurrence during or after prior standard therapy.
- Participants enrolled in this study must provide a written test report confirming RAS mutation or KRAS amplification
- ECOG performance status of 0-1.
- With a life expectancy of ≥12 weeks
- Participants must have at least one measurable lesion other than brain lesions per RECIST 1.1.
- Adequate laboratory parameters during the screening period.
Exclusion Criteria:
- Active brain metastases.
- Known concomitant other targetable driver gene alterations, including but not limited to HER2, BRAF V600E, etc
- Prior treatment with a PAN-RAS inhibitor.
3. Palliative radiotherapy was completed within 28 days before the first dose. 4. Have poorly controlled or severe Gastrointestinal disease. 5. Subjects with active hepatitis B or active hepatitis C. 6. Known allergies to the study drug or its components. 7. Pregnant or lactating women.
Plan d'étude
Comment l'étude est-elle conçue ?
Détails de conception
- Objectif principal: Traitement
- Répartition: Non randomisé
- Modèle interventionnel: Affectation parallèle
- Masquage: Aucun (étiquette ouverte)
Armes et Interventions
Groupe de participants / Bras |
Intervention / Traitement |
|---|---|
|
Expérimental: Phase I:Cohort 1
GFH276+FOLFIRI±bev IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Autres noms:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Autres noms:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Autres noms:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Autres noms:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Autres noms:
|
|
Expérimental: Phase I:Cohort 2
GFH276+ mFOLFOX6±bev IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Autres noms:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Autres noms:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Autres noms:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Autres noms:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Autres noms:
|
|
Expérimental: Phase I:Cohort 3
Cetuximab IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Autres noms:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Autres noms:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Autres noms:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Autres noms:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Autres noms:
|
|
Expérimental: Phase II:Cohort A
GFH276, oral, QD +FOLFIRI/mFOLFOX6±bev, IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Autres noms:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Autres noms:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Autres noms:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Autres noms:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Autres noms:
|
|
Expérimental: Phase II:Cohort B
GFH276, oral, +Cetuximab, IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Autres noms:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Autres noms:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Autres noms:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Autres noms:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Autres noms:
|
|
Comparateur actif: Phase II:Cohort C
FOLFIRI/mFOLFOX6+bev, IV |
Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
Phase Ib: Incidence and severity of AEs and SAEs
Délai: up to 24 months
|
Incidence and severity of AEs and SAEs |
up to 24 months
|
|
Phase Ib: The incidence of DLT events: The incidence of DLT events
Délai: First 28 days
|
The incidence of DLT events |
First 28 days
|
|
Phase II: Objective response rate （ORR）
Délai: From first use of medication to disease progression，up to 24 months
|
Overall Response Rate assessed by investigators according to RECIST 1.1 |
From first use of medication to disease progression，up to 24 months
|
Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
|---|---|---|
|
ORR:
Délai: From first use of medication to disease progression，up to 24 months
|
Overall Response Rate assessed by investigators according to RECIST 1.1 |
From first use of medication to disease progression，up to 24 months
|
|
OS
Délai: From first use of medication to disease progression，up to 24 months
|
Overall Survival |
From first use of medication to disease progression，up to 24 months
|
|
Cmax
Délai: From first use of medication to C6，up to 6 months
|
Maximum plasma concentration |
From first use of medication to C6，up to 6 months
|
|
DOR
Délai: From first use of medication to disease progression，up to 24 months
|
Duration of Response assessed by investigators |
From first use of medication to disease progression，up to 24 months
|
|
DCR
Délai: From first use of medication to disease progression，up to 24 months
|
Disease Control Rate |
From first use of medication to disease progression，up to 24 months
|
|
TTR
Délai: From first use of medication to disease progression，up to 24 months
|
Time To Response assessed by investigators |
From first use of medication to disease progression，up to 24 months
|
|
PFS
Délai: From first use of medication to disease progression，up to 24 months
|
Progression-Free Survival assessed by investigators according to RECIST 1.1 |
From first use of medication to disease progression，up to 24 months
|
|
Tmax
Délai: From first use of medication to C6，up to 6 months
|
Time to Maximum Concentration |
From first use of medication to C6，up to 6 months
|
Collaborateurs et enquêteurs
Parrainer
Les enquêteurs
- Chercheur principal: ruihua xu, MD, Sun Yat-Sen University Cancer Center
Dates d'enregistrement des études
Dates principales de l'étude
Début de l'étude (Estimé)
Achèvement primaire (Estimé)
Achèvement de l'étude (Estimé)
Dates d'inscription aux études
Première soumission
Première soumission répondant aux critères de contrôle qualité
Première publication (Réel)
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
Dernière mise à jour soumise répondant aux critères de contrôle qualité
Dernière vérification
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
- Acides aminés, peptides et protéines
- Protéines
- Produits chimiques organiques
- Composés hétérocycliques, 1 anneau
- Composés hétérocycliques
- Composés hétérocycliques, 2 anneaux
- Composés hétérocycliques, anneau fusionné
- Camptothécine
- Alcaloïdes
- Enzymes et coenzymes
- Anticorps, monoclonal, humanisé
- Anticorps, monoclonal
- Anticorps
- Immunoglobulines
- Immunoprotéines
- Protéines sanguines
- Globulines sériques
- Globulines
- Complexes de coordination
- Pyrimidines
- Formyltétrahydrofolate
- Tétrahydrofolat
- Acide folique
- Pterines
- Ptéridines
- Uracile
- Pyrimidinones
- Coenzymes
- Oxaliplatine
- Bévacizumab
- Irinotécan
- Cétuximab
- Fluorouracile
- Leucovorine
Autres numéros d'identification d'étude
- GFH276X1202
Plan pour les données individuelles des participants (IPD)
Prévoyez-vous de partager les données individuelles des participants (DPI) ?
Informations sur les médicaments et les dispositifs, documents d'étude
Étudie un produit pharmaceutique réglementé par la FDA américaine
Étudie un produit d'appareil réglementé par la FDA américaine
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