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).
Panoramica dello studio
Stato
Condizioni
Intervento / Trattamento
Descrizione dettagliata
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.
Tipo di studio
Iscrizione (Stimato)
Fase
- Fase 2
- Fase 1
Contatti e Sedi
Contatto studio
- Nome: yuting peng, PM
- Numero di telefono: 13730813620
- Email: ytpeng@genfleet.com
Criteri di partecipazione
Criteri di ammissibilità
Età idonea allo studio
Accetta volontari sani
Sessi ammissibili allo studio
Descrizione
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.
Piano di studio
Come è strutturato lo studio?
Dettagli di progettazione
- Scopo principale: Trattamento
- Assegnazione: Non randomizzato
- Modello interventistico: Assegnazione parallela
- Mascheramento: Nessuno (etichetta aperta)
Armi e interventi
Gruppo di partecipanti / Arm |
Intervento / Trattamento |
|---|---|
|
Sperimentale: Phase I:Cohort 1
GFH276+FOLFIRI±bev IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Altri nomi:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Altri nomi:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Altri nomi:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Altri nomi:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Altri nomi:
|
|
Sperimentale: Phase I:Cohort 2
GFH276+ mFOLFOX6±bev IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Altri nomi:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Altri nomi:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Altri nomi:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Altri nomi:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Altri nomi:
|
|
Sperimentale: Phase I:Cohort 3
Cetuximab IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Altri nomi:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Altri nomi:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Altri nomi:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Altri nomi:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Altri nomi:
|
|
Sperimentale: 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 ，
Altri nomi:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Altri nomi:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Altri nomi:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Altri nomi:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Altri nomi:
|
|
Sperimentale: Phase II:Cohort B
GFH276, oral, +Cetuximab, IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Altri nomi:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Altri nomi:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Altri nomi:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Altri nomi:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Altri nomi:
|
|
Comparatore attivo: Phase II:Cohort C
FOLFIRI/mFOLFOX6+bev, IV |
Cosa sta misurando lo studio?
Misure di risultato primarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
Phase Ib: Incidence and severity of AEs and SAEs
Lasso di tempo: 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
Lasso di tempo: First 28 days
|
The incidence of DLT events |
First 28 days
|
|
Phase II: Objective response rate （ORR）
Lasso di tempo: 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
|
Misure di risultato secondarie
Misura del risultato |
Misura Descrizione |
Lasso di tempo |
|---|---|---|
|
ORR:
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
Lasso di tempo: 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
|
Collaboratori e investigatori
Investigatori
- Investigatore principale: ruihua xu, MD, Sun Yat-Sen University Cancer Center
Studiare le date dei record
Studia le date principali
Inizio studio (Stimato)
Completamento primario (Stimato)
Completamento dello studio (Stimato)
Date di iscrizione allo studio
Primo inviato
Primo inviato che soddisfa i criteri di controllo qualità
Primo Inserito (Effettivo)
Aggiornamenti dei record di studio
Ultimo aggiornamento pubblicato (Effettivo)
Ultimo aggiornamento inviato che soddisfa i criteri QC
Ultimo verificato
Maggiori informazioni
Termini relativi a questo studio
Parole chiave
Termini MeSH pertinenti aggiuntivi
- Aminoacidi, peptidi e proteine
- Proteine
- Prodotti chimici organici
- Composti eterociclici, 1-anello
- Composti eterociclici
- Composti eterociclici, 2 anelli
- Composti eterociclici, anello fuso
- Camptothecin
- Alcaloidi
- Enzimi e coenzimi
- Anticorpi, monoclonali, umanizzati
- Anticorpi, monoclonali
- Anticorpi
- Immunoglobuline
- Immunoproteine
- Proteine del sangue
- Globuline sieriche
- Globuline
- Complessi di coordinamento
- Pirimidine
- Formyltetraidrofolates
- Tetraidrofolati
- Acido folico
- Pterins
- Pteridine
- Uracile
- Pirimidinoni
- Coenzimi
- Oxaliplatino
- Bevacizumab
- Irinotecano
- Cetuximab
- Fluorouracile
- Leucovorina
Altri numeri di identificazione dello studio
- GFH276X1202
Piano per i dati dei singoli partecipanti (IPD)
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Informazioni su farmaci e dispositivi, documenti di studio
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