Metastatic Colorectal CancerPhase 1NCT03977090
Geptanolimab(GB226) Combined With Fruquintinib in the Treatment of Metastatic Colorectal Cancer
A Phase 1 study testing Geptanolimab Injection and Fruquintinib in people with Metastatic Colorectal Cancer, run by Genor Biopharma Co., Ltd. at 1 site in China.
Trial summary
This study is a multicenter, dose-escalating phase Ib clinical study to evaluate the safety and tolerability of GB226 in combination with fruquintinib in the treatment of mCRC, evaluate the pharmacokinetic characteristics of GB226 in combined therapy, evaluate immunogenicity of GB226, and explore the antitumor… Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Metastatic Colorectal Cancer
- What is being tested?
- Geptanolimab Injection and Fruquintinib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteChina
- Study dates
- 4 Apr 2019to Dec 2021
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients who meet the following criteria can be enrolled in this study:
- Aged 18 to 75 years, males or females;
- Understand the study procedures and contents, and voluntarily sign the written informed consent form;
- Patients with histologically/pathologically confirmed colorectal cancer;
- Patients with metastatic colorectal cancer, who failed to respond to the previous first-line treatment or above. Treatment failure refers to disease progression or intolerable toxicity after ≥1 cycle of treatment, or relapse during adjuvant or neoadjuvant chemotherapies period or within 6 months after the end of treatment;
- ECOG score of 0-1;
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- Life expectancy≥3 months;
- There is at least one measurable and evaluable tumor lesion (in accordance with RECIST1.1 criteria);
- Systemic chemotherapy, targeted therapies or other anti-tumor biotherapy (tumor vaccine, cytokine or growth factor aimed at controlling tumor) are completed at least 4 weeks before the first dose of investigational product (the oral fluorouracil is discontinued at least 2 weeks ago); systemic or local palliative radiotherapy is completed at least 4 weeks ago; no anti-angiogenic small molecular target drugs are previously received;
- Systemic corticosteroids (prednisone > 10mg/day or equivalent dose) is discontinued at least 2 weeks before the use of the first investigational product;
- The major surgery requiring general anesthesia must be completed at least 8 weeks before the use of the first investigational product; surgery requiring local anesthesia/epidural anesthesia must be completed at least 4 weeks before the use of the first investigational product;
- Routine blood tests require hemoglobin (HGB) ≥90g/L (no transfusion is allowed within 14 days before routine blood tests at baseline), neutrophil count (ANC)≥1.5×109/L (received no supportive treatment with recombinant human granulocyte colony stimulating factor within 14 days before routine blood tests at baseline), platelet ≥100×109/L (received no supportive treatment such as recombinant human thrombopoietin (TPO) or transfusion within 14 days before routine blood tests at baseline);
- Serum creatinine ≤ 1.5×ULN or creatinine clearance ≥ 60 mL/min (calculated based on Cockcroft-Gault formula), and urinary protein ˂ 2+ or ˂1.0g/L; For patients with baseline urinary protein ≥ 2+ or ≥ 1.0g/L, quantitative test of 24h urinary protein will be performed and will be enrolled only when the result ≤ 1.0g/L is obtained.
- Total bilirubin ≤1.5×ULN (unless it is confirmed to have Gilbert's Syndrome), aspartate aminotransferase (AST) and alanine aminotransferase (ALT) ≤2.5×ULN (AST and/or ALT≤5×ULN is allowed for patients with hepatic metastasis);
- Thyroid function variables: thyroid-stimulating hormone (TSH) and free thyroxine (FT3/FT4) are within the normal range; if TSH is not within the normal range, but FT3/FT4 is within the normal range, the subjects can be enrolled.
- The adverse reactions caused by the previous treatment should recover to grade 1 and below before enrollment (except alopecia and ≤ grade 2 neurological toxicity caused by chemotherapy drugs);
- Female subjects who are confirmed not pregnant within 7 days before administration; males or females should agree to adopt medically confirmed effective contraceptive measures during the entire study period and within 6 months after the end of this study.
- Patients can receive follow-up visits as scheduled, well communicate with the investigators and complete the study as required by the study.
Who cannot join
- Any patient fulfilling any of the following exclusion criteria is excluded from this study:
- Active central nervous system (CNS) metastasis, including symptomatic brain metastasis or meningeal metastasis or spinal cord compression etc.; subjects with asymptomatic brain metastasis (no progression within at least 4 weeks after radiotherapy and/or no neurological symptom or sign after surgical resection, treatment with glucocorticoids, antiepileptic drugs, anticonvulsants or mannitol is not necessary) can be enrolled;
- Patients who previously had other malignant tumors (excluding cured cervical carcinoma in situ and skin basal cell carcinoma) are not allowed to participate in the study unless he/she completely relieved at least 2 years before enrollment and requires no other treatment now or during the study period.
- Medical history of active, known autoimmune diseases, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory gastrointestinal disorders, Hashimoto's thyroiditis etc. The following should be excluded: type I diabetes mellitus, hypothyroidism which can be controlled by hormone replacement therapies only, skin diseases requiring no systemic treatment (e.g., vitiligo, psoriasis) and controlled celiac disease;
- Patients who are previously treated with anti PD-1 antibody, anti PD-L1 antibody, anti PD-L2 antibody or anti CTLA-4 antibody (or any other antibodies acting on T cell co-stimulation or checkpoint pathway);
- Uncontrolled hypertension ( systolic blood pressure ≥140mmHg and/or diastolic blood pressure ≥90mmHg) or pulmonary arterial hypertension or unstable angina pectoris; previous presence of myocardial infarction or received coronary artery bypass grafting or coronary stent implantation within 6 months before administration; medical history of chronic heart failure NYHA (New York Heart Association) class 3 and 4; clinically significant valvular heart diseases; subjects with serious arrhythmia requiring treatment, including QTc interval ≥450ms for males and ≥470ms for females (calculated based on Fridericia formula); cerebrovascular accident (CVA) or transient ischemic attack (TIA) within 12 months before administration;
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- Patients who have medical history of arterial thrombosis or deep vein thrombosis within 6 months before the first dose of investigational product, or patients who have evidence or medical history of bleeding tendency within 2 months before the first dose of investigational product, regardless of severity; activated partial thromboplastin time (APTT) or prothrombin time (PT) >1.5×ULN;
- The skin wounds, surgery site, trauma site, serious mucosal ulcer or facture are not completely healed.
- The imaging tests showing the evidence of tumor invasion to large vessels, including tumors which are completely close to, surround or invade to internal cavity of large vessels (e.g., pulmonary artery or superior vena cava);
- Patients with dysphagia or known drug malabsorption;
- Gastrointestinal disorder which may significantly affect absorption of oral drugs or other conditions which may affect gastrointestinal hemorrhage or perforation (e.g., duodenal ulcer, bowel obstruction, acute Crohn's disease, ulcerative colitis, resection of large area of stomach and small intestine etc.) at the discretion of the investigators; Patients who have chronic Crohn's disease and ulcerative colitis (excluding patients with resection of entire colon and rectum), even in non-active stage, should be excluded. Patients with hereditary nonpolyposis colorectal cancer or familial adenomatous polyposis syndrome; Previous medical history of intestinal perforation, intestinal fistula, which is not cured after surgical treatment;
- Subjects with current or previous interstitial lung pneumonia;
- Uncontrolled pleural, peritoneal and pericardial effusion requiring repeated drainage or showing significant symptoms;
- Patients with active infection requiring systemic treatment; active pulmonary tuberculosis (TB) infection;
- Positive human immunodeficiency virus antibody (HIV-Ab); active syphilis; positive hepatitis C antibody (HCV-Ab) and HCV-RNA> the upper limit of normal of the test units; positive hepatitis B surface antigen (HBsAg) and HBV-DNA copies > the upper limit of normal of the test units;
- Patients with complications requiring treatment with immunosuppressive drugs or systemic or local corticosteroids at the immunosuppressive doses (prednisone > 10mg/day or equivalent dose of similar agents);
- It is expected that live vaccines or attenuated vaccines are given 4 weeks before the use of investigational drug, during treatment period or within 5 months after the last dose;
- Subjects who have medical history of drug addiction or drug abuse;
- Lactating women (subjects who agree to stop breastfeeding during the study period can be enrolled);
- Patients who received other investigationsl drugs within 30 days before the use of investigational drug or within 5 half-lives of other investigational drugs (whichever is shorter) or used investigational medical device within 30 days;
- Subjects who are known to be allergic to investigational product or any of its excipients; subjects who are known to have medical history of allergic diseases;
- Subjects who are considered unsuitable for participating in this study at the discretion of the investigator.
Trial locations and contacts
1 site in 1 country.
China1 site, 1 recruiting
- Recruiting
Harbin Medical University Cancer Hospital
Harbin, Heilongjiang, 150081
Yuxian Bai, Doctor, 86 13945095085, bai_yuxian@126.com
Yuxian Bai, Doctor
About this study
Official title: Phase Ib Clinical Trial of Geptanolimab Combined With Fruquintinib in the Treatment of Metastatic Colorectal Cancer
This study is a multicenter, dose-escalating phase Ib clinical study to evaluate the safety and tolerability of GB226 in combination with fruquintinib in the treatment of mCRC, evaluate the pharmacokinetic characteristics of GB226 in combined therapy, evaluate immunogenicity of GB226, and explore the antitumor activity of GB226 in combination with fruquintinib in the treatment of mCRC.
- Conditions
- Metastatic Colorectal Cancer
- Being tested
- Geptanolimab Injection, Fruquintinib
- Medical subject headings
- Colorectal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Geptanolimab InjectionDrug
Also called Recombinant humanized anti-PD-1 monoclonal antibody injection, Geptanolimab
GB226 3mg/kg, q2w, iv.
FruquintinibDrug
Also called HMPL-013
Fruquintinib 3 or 4 or 5mg,qd,po. 3 weeks-on, 1 week-off
| Study group | Role | What they receive |
|---|---|---|
| GB226+Fruquintinib | Experimental | Geptanolimab combined with Fruquintinib Receives: Drug: Geptanolimab Injection; Drug: Fruquintinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Adverse Event
Adverse Event
Measured: up to 52 weeks
Dose Limited Toxicity,DLT
To evaluate the safety of GB226 as defined by dose limited toxicity in patients with metastatic colorectal cancer.
Measured: up to 52 weeks
Extended period recommended dose,RDE
To evaluate the safety of GB226 as defined by extended period recommended dose in patients with metastatic colorectal cancer.
Measured: up to 52 weeks
Secondary outcomes (10)
T max
T max
Measured: up to 52 weeks
C max
C max
Measured: up to 52 weeks
C ss,min
C ss,min
Measured: up to 52 weeks
R C,trough
R C,trough
Measured: up to 52 weeks
Objective Response Rate, ORR
To evaluate the efficacy of GB226 as defined by objective response rate in patients with metastatic colorectal cancer.
Measured: up to 52 weeks
Disease control rate (DCR)
To evaluate the efficacy of GB226 as defined by overall response rate, in patients with metastatic colorectal cancer.
Measured: up to 52 weeks
Duration of response, DOR
To evaluate the duration of response (DOR) of GB242 in patients with metastatic colorectal cancer.
Measured: up to 52 weeks
Progression-free survival, PFS
To evaluate the efficacy of GB226 as defined by progression-free survival in patients with metastatic colorectal cancer.
Measured: up to 52 weeks
Overall survival, OS
To evaluate the duration from the first administration to death because of any reason in patients with metastatic colorectal cancer.
Measured: up to 52 weeks
Antidrug antibody, ADA
Antidrug antibody, ADA
Measured: up to 52 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2019
- Study start4 Apr 2019
- Primary completionDec 2021 (estimated)
- Study completionDec 2021 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Colorectal CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Genor Biopharma Co., Ltd.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Hutchison Medipharma Limited
- Responsible party
- Sponsor
- Investigators
- Yuxian Bai, Principal investigator, Affiliated tumor hospital of Harbin medical university
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03977090
- Sponsor's protocol ID
- Gxplore-012-1
- Status last verified
- Feb 2021
- First submitted
- 24 May 2019
- Last updated
- 10 Feb 2021
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase Ib Clinical Trial of Geptanolimab Combined With Fruquintinib in the Treatment of Metastatic Colorectal Cancer
- ClinicalTrials.gov ID
- NCT03977090
- Acronym / sponsor ID
- Gxplore-012-1
- Conditions
- Metastatic Colorectal Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Genor Biopharma Co., Ltd.Industry (pharma, biotech, devices)
- Collaborators
- Hutchison Medipharma Limited
- Study start
- 4 Apr 2019 (actual)
- Primary completion
- Dec 2021 (estimated)
- Study completion
- Dec 2021 (estimated)
- First posted
- 6 Jun 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study is a multicenter, dose-escalating phase Ib clinical study to evaluate the safety and tolerability of GB226 in combination with fruquintinib in the treatment of mCRC, evaluate the pharmacokinetic characteristics of GB226 in combined therapy, evaluate immunogenicity of GB226, and explore the antitumor activity of GB226 in combination with fruquintinib in the treatment of mCRC.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| GB226+Fruquintinib | Experimental | Drug: Geptanolimab Injection, Drug: FruquintinibGeptanolimab combined with Fruquintinib |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (18 listed)
- Aged 18 to 75 years, males or females;
- Understand the study procedures and contents, and voluntarily sign the written informed consent form;
- Patients with histologically/pathologically confirmed colorectal cancer;
- Patients with metastatic colorectal cancer, who failed to respond to the previous first-line treatment or above. Treatment failure refers to disease progression or intolerable toxicity after ≥1 cycle of treatment, or relapse during adjuvant or neoadjuvant chemotherapies period or within 6 months after the end of treatment;
- ECOG score of 0-1;
Key exclusion criteria (22 listed)
- Any patient fulfilling any of the following exclusion criteria is excluded from this study:
- Active central nervous system (CNS) metastasis, including symptomatic brain metastasis or meningeal metastasis or spinal cord compression etc.; subjects with asymptomatic brain metastasis (no progression within at least 4 weeks after radiotherapy and/or no neurological symptom or sign after surgical resection, treatment with glucocorticoids, antiepileptic drugs, anticonvulsants or mannitol is not necessary) can be enrolled;
- Patients who previously had other malignant tumors (excluding cured cervical carcinoma in situ and skin basal cell carcinoma) are not allowed to participate in the study unless he/she completely relieved at least 2 years before enrollment and requires no other treatment now or during the study period.
- Medical history of active, known autoimmune diseases, including but not limited to systemic lupus erythematosus, psoriasis, rheumatoid arthritis, inflammatory gastrointestinal disorders, Hashimoto's thyroiditis etc. The following should be excluded: type I diabetes mellitus, hypothyroidism which can be controlled by hormone replacement therapies only, skin diseases requiring no systemic treatment (e.g., vitiligo, psoriasis) and controlled celiac disease;
- Patients who are previously treated with anti PD-1 antibody, anti PD-L1 antibody, anti PD-L2 antibody or anti CTLA-4 antibody (or any other antibodies acting on T cell co-stimulation or checkpoint pathway);
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Geptanolimab InjectionAlso: Recombinant humanized anti-PD-1 monoclonal antibody injection, GeptanolimabGB226 3mg/kg, q2w, iv. | Drug | GB226+Fruquintinib |
| FruquintinibAlso: HMPL-013Fruquintinib 3 or 4 or 5mg,qd,po. 3 weeks-on, 1 week-off | Drug | GB226+Fruquintinib |
Primary outcome
Adverse Event
Time frame: up to 52 weeks
Adverse Event
Dose Limited Toxicity,DLT
Time frame: up to 52 weeks
To evaluate the safety of GB226 as defined by dose limited toxicity in patients with metastatic colorectal cancer.
Extended period recommended dose,RDE
Time frame: up to 52 weeks
To evaluate the safety of GB226 as defined by extended period recommended dose in patients with metastatic colorectal cancer.
10 secondary outcomes
T max
Time frame: up to 52 weeks
C max
Time frame: up to 52 weeks
C ss,min
Time frame: up to 52 weeks
R C,trough
Time frame: up to 52 weeks
Objective Response Rate, ORR
Time frame: up to 52 weeks
Disease control rate (DCR)
Time frame: up to 52 weeks
Duration of response, DOR
Time frame: up to 52 weeks
Progression-free survival, PFS
Time frame: up to 52 weeks
Overall survival, OS
Time frame: up to 52 weeks
Antidrug antibody, ADA
Time frame: up to 52 weeks
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2021.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Yuxian Bai principal investigator
Affiliated tumor hospital of Harbin medical university
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Geptanolimab Injection and Fruquintinib in people with Metastatic Colorectal Cancer, run by Genor Biopharma Co., Ltd. at 1 site in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 18 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 10 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Shawn Yu, Master (86-010-85260820, shawn.yu@genorbio.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Adverse Event (time frame: up to 52 weeks). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2021.