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).
Studie Overzicht
Toestand
Conditie
Interventie / Behandeling
Gedetailleerde beschrijving
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.
Studietype
Inschrijving (Geschat)
Fase
- Fase 2
- Fase 1
Contacten en locaties
Studiecontact
- Naam: yuting peng, PM
- Telefoonnummer: 13730813620
- E-mail: ytpeng@genfleet.com
Deelname Criteria
Geschiktheidscriteria
Leeftijden die in aanmerking komen voor studie
Accepteert gezonde vrijwilligers
Geslachten die in aanmerking komen voor studie
Beschrijving
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.
Studie plan
Hoe is de studie opgezet?
Ontwerpdetails
- Primair doel: Behandeling
- Toewijzing: Niet-gerandomiseerd
- Interventioneel model: Parallelle opdracht
- Masker: Geen (open label)
Wapens en interventies
Deelnemersgroep / Arm |
Interventie / Behandeling |
|---|---|
|
Experimenteel: Phase I:Cohort 1
GFH276+FOLFIRI±bev IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Andere namen:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Andere namen:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Andere namen:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Andere namen:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Andere namen:
|
|
Experimenteel: Phase I:Cohort 2
GFH276+ mFOLFOX6±bev IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Andere namen:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Andere namen:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Andere namen:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Andere namen:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Andere namen:
|
|
Experimenteel: Phase I:Cohort 3
Cetuximab IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Andere namen:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Andere namen:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Andere namen:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Andere namen:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Andere namen:
|
|
Experimenteel: 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 ，
Andere namen:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Andere namen:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Andere namen:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Andere namen:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Andere namen:
|
|
Experimenteel: Phase II:Cohort B
GFH276, oral, +Cetuximab, IV, |
Phase Ib - Dose Escalation Cohort 1 GFH276 in combination with FOLFIRI±bev, (bevacizumab): Irinotecan 、Leucovorin ， Fluorouracil ，
Andere namen:
Phase Ib - Dose Escalation Cohort 2 GFH276, QD. in combination with mFOLFOX6±bev, mFOLFOX6: Oxaliplatin, Leucovorin, Fluorouracil bev (bevacizumab)
Andere namen:
Phase II Cohort B：GFH276, oral, QD + Cetuximab, Cetuximab:
Andere namen:
Phase II Cohort A：GFH276, oral +FOLFIRI/mFOLFOX6±bev, IV, Q4W, d1,d15
Andere namen:
Phase Ib - Dose Escalation Cohort 3：GFH276 in combination with cetuximab， Cetuximab:
Andere namen:
|
|
Actieve vergelijker: Phase II:Cohort C
FOLFIRI/mFOLFOX6+bev, IV |
Wat meet het onderzoek?
Primaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
Phase Ib: Incidence and severity of AEs and SAEs
Tijdsspanne: 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
Tijdsspanne: First 28 days
|
The incidence of DLT events |
First 28 days
|
|
Phase II: Objective response rate （ORR）
Tijdsspanne: 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
|
Secundaire uitkomstmaten
Uitkomstmaat |
Maatregel Beschrijving |
Tijdsspanne |
|---|---|---|
|
ORR:
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
Tijdsspanne: 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
|
Medewerkers en onderzoekers
Onderzoekers
- Hoofdonderzoeker: ruihua xu, MD, Sun Yat-Sen University Cancer Center
Studie record data
Bestudeer belangrijke data
Studie start (Geschat)
Primaire voltooiing (Geschat)
Studie voltooiing (Geschat)
Studieregistratiedata
Eerst ingediend
Eerst ingediend dat voldeed aan de QC-criteria
Eerst geplaatst (Werkelijk)
Updates van studierecords
Laatste update geplaatst (Werkelijk)
Laatste update ingediend die voldeed aan QC-criteria
Laatst geverifieerd
Meer informatie
Termen gerelateerd aan deze studie
Trefwoorden
Aanvullende relevante MeSH-voorwaarden
- Aminozuren, peptiden en eiwitten
- Eiwitten
- Organische chemicaliën
- Heterocyclische verbindingen, 1-ring
- Heterocyclische verbindingen
- Heterocyclische verbindingen, 2-ring
- Heterocyclische verbindingen, gefuseerd ring
- Camptothecin
- Alkaloïden
- Enzymen en co -enzymen
- Antilichamen, monoklonaal, gehumaniseerd
- Antilichamen, monoklonaal
- Antilichamen
- Immunoglobulinen
- Immunoproteïnen
- Bloedeiwitten
- Serum -globulines
- Globulines
- Coördinatiecomplexen
- Pyrimidines
- Formyltetrahydrofolates
- Tetrahydrofolaten
- Foliumzuur
- Pterins
- Pteridines
- Uracil
- Pyrimidinonen
- Co -enzymen
- Oxaliplatine
- Bevacizumab
- Irinotecan
- Cetuximab
- Fluorouracil
- Leucovorin
Andere studie-ID-nummers
- GFH276X1202
Plan Individuele Deelnemersgegevens (IPD)
Bent u van plan om gegevens van individuele deelnemers (IPD) te delen?
Informatie over medicijnen en apparaten, studiedocumenten
Bestudeert een door de Amerikaanse FDA gereguleerd geneesmiddel
Bestudeert een door de Amerikaanse FDA gereguleerd apparaatproduct
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