Clinical Trials /

A Clinical Study to Evaluate Efficacy and Safety of HLX10 Combined With HLX04 and Chemotherapy (XELOX) in Patients With Metastatic Colorectal Cancer (mCRC)

NCT04547166

Description:

This is a two-arm, randomized, double-blinded, multicenter phase III clinical study to evaluate the clinical efficacy of HLX10 combined with HLX04 and XELOX chemotherapy versus placebo combined with Avastin® and XELOX chemotherapy in first-line treatment of patients with mCRC.

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: A Clinical Study to Evaluate Efficacy and Safety of HLX10 Combined With HLX04 and Chemotherapy (XELOX) in Patients With Metastatic Colorectal Cancer (mCRC)
  • Official Title: A Randomized, Double-blind, Multicenter, Phase III Clinical Study of HLX10 (Recombinant Humanized Anti-PD-1 Monoclonal Antibody) in Combination With HLX04 (Recombinant Humanized Anti-VEGF Monoclonal Antibody) and Chemotherapy (XELOX) Versus Placebo in Combination With Avastin® and Chemotherapy (XELOX) in First-line Treatment of Patients With Metastatic Colorectal Cancer (mCRC)

Clinical Trial IDs

  • ORG STUDY ID: HLX10-015-CRC301
  • NCT ID: NCT04547166

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
HLX10/PlaceboHLX10 + HLX04
HLX04/Avastinplacebo + Avastin ®

Purpose

This is a two-arm, randomized, double-blinded, multicenter phase III clinical study to evaluate the clinical efficacy of HLX10 combined with HLX04 and XELOX chemotherapy versus placebo combined with Avastin® and XELOX chemotherapy in first-line treatment of patients with mCRC.

Trial Arms

NameTypeDescriptionInterventions
HLX10 + HLX04Experimental
  • HLX10/Placebo
placebo + Avastin ®Placebo Comparator
  • HLX04/Avastin

Eligibility Criteria

        Inclusion Criteria:

          -  Patients are eligible for the study if they meet all of the following criteria:

               1. Male or female aged 18-75 years (inclusive) at the time of signing the informed
                  consent form (ICF)

               2. Histopathologically confirmedunresectable metastatic/recurrent colorectal
                  adenocarcinoma

               3. Expected survival ≥ 12 weeks

               4. Have not received any previous systemic antineoplastic drug therapy for
                  metastatic/recurrent colorectal adenocarcinoma

               5. Time from last treatment to recurrence or progression ≥ 12 monthsforpatients who
                  have previously received neoadjuvant/adjuvant therapy

               6. Time from the end of previous traditional Chinese medicine to the first dose of
                  the study drugs ≥ 2 weeks

               7. 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)

               8. 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)

               9. Paitent agrees to provide sufficient archival tumor tissue specimen or perform
                  biopsy for determination of PD-L1 expression and second generation genome
                  sequencing

              10. ECOG PS score of 0-1 within 7 days prior to the first dose of the studydrugs

              11. 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)

              12. 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)

              13. 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

              14. 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

              15. 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:

               1. 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

               2. Presence of central nervous system (CNS) or leptomeningeal metastases

               3. 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

               4. 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.)

               5. 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

               6. Known history of severe allergy to any monoclonal antibody or study drug
                  excipients

               7. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring
                  frequent drainage after appropriate intervention

               8. 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)

               9. 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

              10. 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

              11. History of active tuberculosis

              12. 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

              13. 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

              14. Treatment with live attenuated vaccine within 28 days before the first dose of
                  study drug

              15. 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

              16. 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

              17. 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

              18. Have previously received intestinal stent implantation and the intestinal stent
                  has not been explanted until screening

              19. 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

              20. Prior history of hypertensive crisis or hypertensive encephalopathy

              21. CT/MRI images showing tumor encircling or invading a large vascular lumen (e.g.,
                  pulmonary artery or superior vena cava)

              22. 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

              23. Currently receiving or have received aspirin (> 325mg/day) or dipyridamole,
                  ticlopidine, clopidogrel, and cilostazol within 7 days before the first dose of
                  study drugs

              24. 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

              25. 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

              26. Evidence showing the presence of meteorismthat cannot be explained by puncture or
                  recent surgery

              27. Presence of severe, unhealed or split wounds and active ulcers or untreated
                  fractures

              28. Presence of any of the following medical conditions within 6 months prior to the
                  first dose of study drugs:

                    1. Gastrointestinal bleeding (macroscopic melena, bloody stool, etc., except
                       for hemorrhoidal bleeding)

                    2. 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

                    3. 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

                    4. Intra-abdominal inflammation, including but not limited to peptic ulcer,
                       diverticulitis or colitis

                    5. Major vascular disease (e.g., aortic aneurysm requiring surgical repair or
                       associated with recent peripheral artery thrombosis)

              29. Known history of psychotropic substance abuse or drug use

              30. 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

              31. Pregnant or lactating women

              32. 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
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:PFS
Time Frame:from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years
Safety Issue:
Description:Progression-free survival (assessed by independent radiological review committee (IRRC) based on RECIST v1.1)

Secondary Outcome Measures

Measure:OS
Time Frame:from the date of first dose unitl the date of death from any cause,assessed up to 2 years
Safety Issue:
Description:Overall survival (OS)
Measure:PFS
Time Frame:from the first dose until firstly confirmed and recorded disease progression or death (whichever occurs earlier),assessed up to 2 years
Safety Issue:
Description:Progression-free survival (assessed by independent radiological review committee (IRRC) based on iRECIST,by the investigators based on RECIST v1.1))
Measure:ORR
Time Frame:up to 2 years
Safety Issue:
Description:Objective response rate (assessed by independent radiological review and the investigators based on RECIST v1.1))
Measure: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
Safety Issue:
Description:Duration of response
Measure:DCR
Time Frame:the proportion of patients with the best overall response of CR, PR, or stable disease (SD) persisting for 12 weeks
Safety Issue:
Description:Disease control rate

Details

Phase:Phase 3
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Shanghai Henlius Biotech

Last Updated

September 7, 2020