- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04547166
A Clinical Study to Evaluate Efficacy and Safety of Serplulimab(HLX10) Combined With Bevacizumab(HLX04) and Chemotherapy (XELOX) in Patients With Metastatic Colorectal Cancer (mCRC)
A Randomized, Double-blind, Multicenter, PhaseⅡ/Ⅲ Clinical Study of Serplulimab (HLX10) in Combination With Bevacizumab (HLX04) and Chemotherapy (XELOX) Versus Placebo in Combination With Bevacizumab (HLX04) and Chemotherapy (XELOX) in First-line Treatment of Patients With Metastatic Colorectal Cancer (mCRC)
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Patients with confirmed unresectable metastatic/recurrent colorectal adenocarcinoma who have not received systemic anti-neoplastic therapy for metastatic/recurrent lesions will be included in this study.Approximately 6-12 patients will be enrolled in the Part I (Safety Run-in Period).Approximately 100 patients will be enrolled in the Part II (Phase II study, 50 in the test group and 50 in the control group).Approximately 654 patients will be enrolled in the Part III (Phase III study, 327 in the test group and 327 in the control group).
Part II (Phase II study): Approximately 40 study sites in China will participate.
Part III (Phase III study): A total of approximately 75 study sites in 7 countries(including China, the United States, Brazil, Indonesia, Russia, Poland, Spain, etc.) will participate.
The study consists of a screening period (up to 28 days), a treatment period (3-week cycle, up to 2 years), and a follow-up period (including a safety follow-up period, and a survival follow-up every 12 weeks).
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 3
Contacts and Locations
Study Locations
-
-
-
Linyi, China
- Linyi Cancer Hospital
-
Shanghai, China
- Fudan University Affiliated Oncology Hospital
-
-
Guangdong
-
Guangzhou, Guangdong, China, 510075
- Center for Cancer Prevention and Treatment of Sun Yat-sen University
-
-
Zhejiang
-
Hangzhou, Zhejiang, China, 310022
- Zhejiang Cancer Hospital
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
Patients are eligible for the study if they meet all of the following criteria:
- Male or female aged 18-75 years (inclusive) at the time of signing the informed consent form (ICF)
- Histopathologically confirmedunresectable metastatic/recurrent colorectal adenocarcinoma
- Expected survival ≥ 12 weeks
- Have not received any previous systemic antineoplastic drug therapy for metastatic/recurrent colorectal adenocarcinoma
- Time from last treatment to recurrence or progression ≥ 12 monthsforpatients who have previously received neoadjuvant/adjuvant therapy
- Time from the end of previous traditional Chinese medicine to the first dose of the study drugs ≥ 2 weeks
- Recovering to ≤ Grade 1 of any AE related with the previous treatment according to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) (except for alopecia)
- At least one measurable lesion assessed by central imaging according to RECIST v1.1, the measurable lesion should not have received local treatment such as radiotherapy (lesions located in the previous irradiated area may also be considered as acceptable measurable lesions if progression is confirmed)
- Paitent agrees to provide sufficient archival tumor tissue specimen or perform biopsy for determination of PD-L1 expression and second generation genome sequencing
- ECOG PS score of 0-1 within 7 days prior to the first dose of the studydrugs
- Negative (-) hepatitis B surface antigen (HBsAg), negative (-) hepatitis B core antibody (HBcAb), and the absence of active hepatitis as clinically determined. In case of positive (+) HBsAg or HBcAb, hepatitis B virus deoxyribonucleic acid (HBV-DNA) should be < 1000 copies/mL or 200 IU/mL before enrollment (if the lower limit of detection of the study site is > 200 IU/mL, patient with HBV-DNA below the lower limit of detection is allowed to be enrolled)
- Negative (-) hepatitis C virus (HCV) antibody; in case of positive (+) HCV antibody, a negative HCV-RNA test is required for enrollment. Patients with co-infection with hepatitis B and C should be excluded (positive for HBsAg or HBcAb and positive for HCV antibody)
- Adequate major organs function as indicated by the following laboratory criteria (no treatment with blood transfusions, albumin, recombinant human thrombopoietin, or colony-stimulating factor [CSF] within 14 days prior to the first dose of study drugs): Hematological System:Neutrophils (ANC): ≥ 1.5×10 9 /L; Platelets (PLT) ≥ 100×10 9 /L;Hemoglobin (Hb) ≥ 90g/L Hepatic Function:Total bilirubin (TBIL) ≤ 1.5×upper limit of normal(ULN) Glutamate aminotransferase (ALT) : ≤ 2.5×ULN; ≤ 5.0×ULN for patients with liver metastases Aspartate aminotransferase (AST) ≤ 2.5×ULN; ≤ 5.0×ULN for patients with liver metastases Alkaline Phosphatase(ALP): ≤ 2.5×ULN; ≤ 5.0×ULN for patients with liver and/or bone metastases; Albumin ≥ 30 g/L Renal Function: Creatinine (Cr) ≤ 1.5×ULN; Creatinine clearance ≥ 50mL/min if Cr > 1.5 × ULN; (Calculated by Cockcroft-Gault formula) Coagulation Activated partial thromboplastin time(APTT) ≤ 1.5×ULN Prothrombin time (PT) ≤ 1.5×ULN International Normalized Ratio (INR) ≤ 1.5×ULN Urinalysis/24-hour urine protein Urine protein Qualitative examination on urine protein ≤ 1+; in case of ≥ 2+, a 24-hour urine protein test will be required, and if the 24-hour urine protein is <1g, the enrollment will be allowed
- Female patients of childbearing potential should have a negative serum pregnancy test within 7 days prior to the first dose of study drugs. For female patients of childbearing potential, and male patients with partners of childbearing potential, at least one medically acceptable contraceptive measure (e.g., intrauterine device, contraceptives or condom) is required and will continue for the duration of the study treatment, and for at least 3 months after the last dose of HLX10/placebo, HLX04/Avastin ® , and for at least 6 months after the last dose of chemotherapy, whichever occurs later
- Provide signed ICF and is willing to comply with all study procedures and rules as specified in the protocol
Exclusion Criteria:
Patients will be excluded from the study if they meet any of the following exclusion criteria:
- Other active malignancies within 5 years prior to the first dose of study drugs. Patients with localized tumors that have been cured, such as basal cell carcinoma of skin, squamous cell carcinoma of skin, superficial bladder cancer, carcinoma in situ of prostate, carcinoma in situ of cervix, carcinoma in situ of breast, etc., may be enrolled in the study
- Presence of central nervous system (CNS) or leptomeningeal metastases
- Radiation therapy within 6 months prior to initiation of study treatment with the exception of palliative radiation therapy for bone disorders at least 14 days prior to initiation of study treatment; radiation therapy covering more than 30% of the bone marrow area within 28 days prior to the first dose is not allowed
- Prior postoperative adjuvant therapy with targeted agents targeting EGFR or VEGF/vascular endothelial growth factor receptor (VEGFR) (including bevacizumab, cetuximab, panitumumab, aflibercept, regorafenib, or biosimilars of these agents, etc.)
- Prior treatment with any T-cell costimulation or immune checkpoint inhibitors, including but not limited to CTLA-4 inhibitors, PD-1 inhibitors, PD-L1/2 inhibitors, or other drugs targeting T cells
- Known history of severe allergy to any monoclonal antibody or study drug excipients
- Uncontrolled pleural effusion, pericardial effusion, or ascites requiring frequent drainage after appropriate intervention
- Cerebrovascular accident, myocardial infarction, unstable angina, poorly controlled arrhythmia (including QTc interval ≥ 450 ms in males and ≥ 470 ms in females) within 6 months (QTc interval is calculated by Fridericia's formula)
- A cardiac insufficiency of Grade III or IV according to the New York Heart Association (NYHA) criteria, or a left ventricular ejection fraction (LVEF) < 50% based on echocardiography
- Known history of immunodeficiency, including positive human immunodeficiency virus (HIV) antibody test, or other acquired, congenital immunodeficiency disorders, or history of organ transplantation and allogeneic bone marrow transplantation
- History of active tuberculosis
- Patients with previous and current interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonia, severely impaired lung function, etc. that may interfere with the detection and management of suspected drug-related pulmonary toxicity
- Patients with currently active or a history of autoimmune diseases (e.g., interstitial pneumonia, colitis, hepatitis, hypophysitis, vasculitis, nephritis, hyperthyroidism, hypothyroidism, including but not limited to these diseases or syndromes). The following patients are allowed: patients with vitiligo or recovered childhood asthma/allergy without need of any intervention in adulthood; patients with autoimmune- mediated hypothyroidism treated with a stable dose of thyroid replacement hormone; patients with type I diabetes mellitus with a stable dose of insulin
- Treatment with live attenuated vaccine within 28 days before the first dose of study drug
- Patients who require continuous (for > 7 days) systemic treatment with corticosteroids (> 10mg/day prednisone or equivalents) or other immunosuppressive agents within 14 days before the first dose of study drug or during the study period. Inhaled or topical steroids or adrenal replacement at doses ≤ 10mg/day prednisone or equivalent dose are permitted in the absence of active autoimmune disease
- Severe infection (CTCAE>Grade 2) occurred within 4 weeks prior to the first dose of study drugs, such as severe pneumonia, bacteremia and infection complications requiring hospitalization; active pulmonary inflammation accompanied with relevant clinical symptoms or signs based on chest X-ray at baseline; symptoms and signs of infection requiring oral or intravenous antibiotic therapy within 2 weeks prior to the first dose of study drugs, except prophylactic use of antibiotics
- Major surgery within 28 days prior to the first dose of study drugs. A major surgery is defined as a surgery that takes at least 3 weeks of postoperative recovery before receiving treatment in this study
- Have previously received intestinal stent implantation and the intestinal stent has not been explanted until screening
- Inadequately controlled hypertension (defined as systolic blood pressure ≥ 150 mmHg and/or diastolic blood pressure ≥ 100 mmHg) after more than 2 years of antihypertensive therapy
- Prior history of hypertensive crisis or hypertensive encephalopathy
- CT/MRI images showing tumor encircling or invading a large vascular lumen (e.g., pulmonary artery or superior vena cava)
- Bleeding outside the gastrointestinal tract (including hemoptysis, abnormal vaginal bleeding, etc.) at screening, or Grade 2 bleeding outside the gastrointestinal tract within 3 months, or Grade 3 or higher bleeding outside the gastrointestinal tract within 6 months prior to signing the ICF
- Currently receiving or have received aspirin (> 325mg/day) or dipyridamole, ticlopidine, clopidogrel, and cilostazol within 7 days before the first dose of study drugs
- Currently receving or have received full-dose of anticoagulants or thrombolytic agents via oral or injection for therapeutic purposes within 7 days prior to the first dose of study drugs. Prophylactic anticoagulation therapyis allowed for open intravenous infusion systems as long as the international normalized ratio (INR) < 1.5×ULN) and partial thromboplastin time (APTT) is within normal range thereafter within 14 days prior to the first dose of study drug. Prophylactic use of low molecular weight heparin (i.e. enoxaparin at 40mg/day) is allowed
- Long-term treatment with daily administration of nonsteroidal anti-inflammatory drugs (NSAIDs). Occasional use of NSAIDs to relieve medical symptoms such as headache or fever is allowed
- Evidence showing the presence of meteorismthat cannot be explained by puncture or recent surgery
- Presence of severe, unhealed or split wounds and active ulcers or untreated fractures
Presence of any of the following medical conditions within 6 months prior to the first dose of study drugs:
- Gastrointestinal bleeding (macroscopic melena, bloody stool, etc., except for hemorrhoidal bleeding)
- Abdominal or tracheoesophageal fistula, gastrointestinal perforation or intra-abdominalabscess, massive ascites identified by investigator (defined as patients requiring drainage or management within 2 weeks), or significant peritoneal metastases
- Intestinal obstruction and/or previous clinical signs or symptoms of gastrointestinal obstruction, including incomplete obstruction associated with a preexisting disease or requiring routine parenteral hydration, parenteral nutrition, or tube feeding. Patients with incomplete obstruction/obstruction syndrome/signs or symptoms of intestinal obstruction at the time of initial diagnosis may be eligible for study enrollment if they receive definitive (surgical) treatment to resolve symptoms
- Intra-abdominal inflammation, including but not limited to peptic ulcer, diverticulitis or colitis
- Major vascular disease (e.g., aortic aneurysm requiring surgical repair or associated with recent peripheral artery thrombosis)
- Known history of psychotropic substance abuse or drug use
- Participating in another clinical study, or have completed the treatment of another clinical study within 14 days before the planned study treatment in this study
- Pregnant or lactating women
- Any other factors that may lead to study discontinuation assessed by the investigator, such as other severe diseases (including mental disease) that require concomitant therapy, seriousabnormalities in laboratory findings, family or social factors, and other conditions possibly affecting the safety or study data collection of the patient
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Serplulima +Bevacizumab+XELOX
Serplulimab (HLX10) in Combination With Bevacizumab and chemotherapy (XELOX)
|
a single fixed dose of 300 mg, intravenous infusion (IV), every 3 weeks (Day 1 of each cycle [D1]), non-reducible.
Other Names:
7.5mg/kg, IV, every 3 weeks (D1 of each cycle), non-reducible.
Other Names:
|
Placebo Comparator: placebo + Bevacizumab+XELOX
placebo in combination with Bevacizumab and chemotherapy (XELOX)
|
7.5mg/kg, IV, every 3 weeks (D1 of each cycle), non-reducible.
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
PFS
Time Frame: from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years
|
Progression-free survival (assessed by independent radiological review committee (IRRC) based on RECIST v1.1)
|
from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
OS
Time Frame: from the date of first dose unitl the date of death from any cause,assessed up to 2 years
|
Overall survival (OS)
|
from the date of first dose unitl the date of death from any cause,assessed up to 2 years
|
PFS
Time Frame: from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years
|
Progression-free survival (assessed by independent radiological review committee (IRRC) based on iRECIST,by the investigators based on RECIST v1.1))
|
from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years
|
ORR
Time Frame: up to 2 years
|
Objective response rate (assessed by independent radiological review and the investigators based on RECIST v1.1))
|
up to 2 years
|
Duration of response
Time Frame: from the date when CR or PR (whichever recorded earlier) is firstly achieved until the date when disease progression or death is firstly recorded (whichever occurs earlier),assessed up to 2 years
|
Duration of response
|
from the date when CR or PR (whichever recorded earlier) is firstly achieved until the date when disease progression or death is firstly recorded (whichever occurs earlier),assessed up to 2 years
|
DCR
Time Frame: the proportion of patients with the best overall response of CR, PR, or stable disease (SD) persisting for 12 weeks
|
Disease control rate
|
the proportion of patients with the best overall response of CR, PR, or stable disease (SD) persisting for 12 weeks
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms
- Neoplasms by Site
- Gastrointestinal Neoplasms
- Digestive System Neoplasms
- Gastrointestinal Diseases
- Colonic Diseases
- Intestinal Diseases
- Intestinal Neoplasms
- Rectal Diseases
- Colorectal Neoplasms
- Physiological Effects of Drugs
- Antineoplastic Agents
- Antineoplastic Agents, Immunological
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Bevacizumab
Other Study ID Numbers
- HLX10-015-CRC301
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Metastatic Colorectal Cancer
-
Mayo ClinicCompletedMetastatic Colorectal Adenocarcinoma | Metastatic Colon Adenocarcinoma | Metastatic Colorectal Carcinoma | Metastatic Rectal Adenocarcinoma | Stage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Metastatic... and other conditionsUnited States
-
Hutchison Medipharma LimitedActive, not recruitingMetastatic Colorectal Cancer | Metastatic Colon CancerUnited States, Spain, Japan, Australia, Austria, Belgium, Czechia, Estonia, France, Germany, Hungary, Italy, Poland, United Kingdom
-
Emory UniversityBristol-Myers Squibb; National Cancer Institute (NCI); National Institutes of...Active, not recruitingColorectal Cancer Metastatic | Colorectal Adenocarcinoma | Stage IV Colorectal Cancer | Stage IVA Colorectal Cancer | Stage IVB Colorectal Cancer | Refractory Colorectal Carcinoma | Metastatic Microsatellite Stable Colorectal Carcinoma | Stage IVC Colorectal CancerUnited States
-
Array Biopharma, now a wholly owned subsidiary...CompletedMetastatic Colorectal Cancer | Advanced Solid Tumors | Advanced or Metastatic Biliary CancerUnited States
-
Zhejiang Cancer HospitalNot yet recruitingMetastatic Colorectal Cancer | Metastatic Colorectal Adenocarcinoma | CRCChina
-
AmgenCompletedCancer | Metastatic Colorectal Cancer | Colorectal Cancer | Rectal Cancer | Metastatic Cancer | Colon Cancer
-
Academic and Community Cancer Research UnitedNational Cancer Institute (NCI)Active, not recruitingMetastatic Pancreatic Adenocarcinoma | Stage IV Pancreatic Cancer AJCC v6 and v7 | Stage IV Colorectal Cancer AJCC v7 | Stage IVA Colorectal Cancer AJCC v7 | Stage IVB Colorectal Cancer AJCC v7 | Metastatic Gastroesophageal Junction Adenocarcinoma | Metastatic Colorectal Carcinoma | Metastatic Malignant... and other conditionsUnited States
-
Dana-Farber Cancer InstituteAmerican Cancer Society, Inc.Not yet recruitingMetastatic Colorectal Cancer | Colorectal Cancer | Metastatic Colon CancerUnited States
-
Symphogen A/STerminatedCarcinoma | Metastatic Colorectal Cancer | Colorectal Cancer MetastaticUnited States, Spain, Germany, Italy
-
AmgenCompletedCancer | Metastatic Colorectal Cancer | Colorectal Cancer | Rectal Cancer | Metastatic Cancer | Colon Cancer | Oncology
Clinical Trials on HLX10
-
Shanghai Henlius BiotechRecruitingSquamous Non-small-cell Lung CancerChina
-
Shandong UniversityRecruiting
-
Zhejiang Cancer HospitalRecruitingExtensive Stage Lung Small Cell CancerChina
-
Shanghai Henlius BiotechRecruitingNon Small Cell Lung CancerChina
-
Shanghai Henlius BiotechUnknown
-
RenJi HospitalShanghai Zhongshan HospitalNot yet recruitingFirst-line Treatment of Non-clear Renal Cell Carcinoma
-
Shanghai Henlius BiotechRecruitingAdvanced or Metastatic Solid TumorsAustralia
-
Shanghai Henlius BiotechNot yet recruiting
-
Shanghai Henlius BiotechRecruiting
-
Henlix, IncUnknown