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A Study of HLX10 in Combination With Carboplatin Plus (+) Pemetrexed With or Without HLX04 Compared With Carboplatin+Pemetrexed in 1L Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

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ClinicalTrials.gov Identifier: NCT03952403
Recruitment Status : Recruiting
First Posted : May 16, 2019
Last Update Posted : May 12, 2020
Sponsor:
Information provided by (Responsible Party):
Shanghai Henlius Biotech

Tracking Information
First Submitted Date  ICMJE May 6, 2019
First Posted Date  ICMJE May 16, 2019
Last Update Posted Date May 12, 2020
Actual Study Start Date  ICMJE December 2, 2019
Estimated Primary Completion Date June 24, 2022   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 9, 2020)
  • Number of participants with treatment-related adverse events as assessed by CTCAE v5.0 [ Time Frame: baseline to 21 days ]
  • Part 2-Progression Free Survival (PFS) as Determined by the IRRC using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Baseline until disease progression or death, whichever occurs first (up to approximately 24months) ]
Original Primary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • Number of participants with treatment-related adverse events as assessed by CTCAE v4.03 [ Time Frame: baseline to 21 days ]
  • Part 2-Progression Free Survival (PFS) as Determined by the IRRC using Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) [ Time Frame: Baseline until disease progression or death, whichever occurs first (up to approximately 24months) ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 16, 2019)
  • Part 1 and 2-Incidence rates of AEs and SAEs [ Time Frame: Baseline up to approximately 27months ]
  • Part 1 and 2-Overall Survival (OS) [ Time Frame: Baseline until death (up to approximately 36 months) ]
  • Part 1-PFS (assessed by the investigator according to RECIST v1.1) [ Time Frame: Baseline until disease progression or death, whichever occurs first (up to approximately 36months) ]
  • Part 1 and 2-Objective response rate (ORR, assessed by IRRC and investigator according to RECIST v1.1 criteria) [ Time Frame: Baseline up to approximately 24 months ]
  • Part 1 and 2-Duration of response (DOR, assessed by IRRC and investigator according to RECIST v1.1 criteria) [ Time Frame: Baseline up to approximately 36 months ]
  • Part 1 and 2-Pharmacokinetics (PK): serum HLX10 concentration [ Time Frame: Baseline up to approximately 25 months ]
  • Part 1 and 2-Immunogenicity evaluation: positive anti-drug antibody (ADA) rate [ Time Frame: Baseline up to approximately 25 months ]
  • Part 1 and 2-PD-L1 expression level [ Time Frame: Baseline ]
  • Part 1 and 2-Microsatellite instability(MSI) [ Time Frame: Baseline ]
  • Part 1 and 2-Tumor mutation burden(TMB) [ Time Frame: Baseline ]
Original Secondary Outcome Measures  ICMJE
 (submitted: May 14, 2019)
  • Part 1 and 2-Incidence rates of AEs and SAEs [ Time Frame: Baseline up to approximately 27months ]
  • Part 1 and 2-Overall Survival (OS) [ Time Frame: Baseline until death (up to approximately 36 months) ]
  • Part 1-PFS (assessed by the investigator according to RECIST v1.1) [ Time Frame: Baseline until disease progression or death, whichever occurs first (up to approximately 36months) ]
  • Part 1 and 2-Objective response rate (ORR, assessed by IRRC and investigator according to RECIST v1.1 criteria) [ Time Frame: Baseline up to approximately 24 months ]
  • Part 1 and 2-Duration of response (DOR, assessed by IRRC and investigator according to RECIST v1.1 criteria) [ Time Frame: Baseline up to approximately 36 months ]
  • Part 1 and 2-Pharmacokinetics (PK): serum HLX10 concentration [ Time Frame: Baseline up to approximately 25 months ]
  • Part 1 and 2-Immunogenicity evaluation: positive anti-drug antibody (ADA) rate [ Time Frame: Baseline up to approximately 25 months ]
  • Part 1 and 2-PD-L1 expression level [ Time Frame: Baseline ]
  • Part 1 and 2-Microsatellite instability(MSI) [ Time Frame: Baseline ]
  • Part 1 and 2-Tumor mutation burden(TMB) [ Time Frame: Baseline ]
  • Part 1 and 2- Quality of life assessment [ Time Frame: Baseline up to approximately 24 months ]
    EORTC QLQ-C30
  • Part 1 and 2- Quality of life assessment [ Time Frame: Baseline up to approximately 24 months ]
    EQ-5D-5L
  • Part 1 and 2- Quality of life assessment [ Time Frame: Baseline up to approximately 24 months ]
    EORTC QLQ-LC13
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of HLX10 in Combination With Carboplatin Plus (+) Pemetrexed With or Without HLX04 Compared With Carboplatin+Pemetrexed in 1L Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
Official Title  ICMJE A Three Arm, Randomized, Double-Blind, Multicenter, Phase 3 Study of HLX10(Anti-PD-1 Antibody) in Combination With Carboplatin Plus (+) Pemetrexed With or Without HLX04(Avastin Biosimilar) Compared With Carboplatin+Pemetrexed in 1L Stage IIIB/IIIC or IV Non-Squamous Non-Small Cell Lung Cancer (NSCLC)
Brief Summary This study involves a two-part design. Part 1 is designed to evaluate the safety and tolerability of the 4 drug (HLX10+HLX04+carboplatin+pemetrexed). Part 2 is a randomized, open-label study, which will evaluate the safety and efficacy of HLX10 in combination with carboplatin+pemetrexed with or without HLX04(biosimilar of avastin) compared with treatment with carboplatin+pemetrexed in 1st line Stage IIIB/IIIC or IV non-squamous NSCLC. Participants will be randomized in a 1:1:1 ratio to Arm A (HLX10+HLX04+Carboplatin+Pemetrexed), Arm B (HLX10+Carboplatin+Pemetrexed), or Arm C (Carboplatin+Pemetrexed).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma
  • Non-Small-Cell Lung
Intervention  ICMJE
  • Drug: HLX10, an engineered anti-PD-1 antibody
    HLX10 will be administered as IV infusion at a dose of 4.5mg/kg on Day 1 of each 21-day cycle until loss of clinical benefit or up to 2 year.
  • Drug: HLX04, a bevacizumab biosimilar
    HLX04 will be administered as IV infusion at a dose of 15 milligrams per kilogram (mg/kg) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, death or up to 2 year.
  • Drug: Carboplatin
    Carboplatin will be administered at area under the concentration-time curve (AUC) 5 on Day 1 of each 21-day cycle for 4 cycles, or until loss of clinical benefit whichever occurs first.
  • Drug: Pemetrexed
    Pemetrexed will be administered as IV infusion at a dose of 500 milligrams per square meter (mg/m2) on Day 1 of each 21-day cycle until progressive disease, unacceptable toxicity, death or up to 2 year.
Study Arms  ICMJE
  • Experimental: Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed)
    Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
    Interventions:
    • Drug: HLX10, an engineered anti-PD-1 antibody
    • Drug: HLX04, a bevacizumab biosimilar
    • Drug: Carboplatin
    • Drug: Pemetrexed
  • Experimental: Part 2-Arm A (HLX10+HLX04+Carboplatin+Pemetrexed)
    Participants will receive IV infusion of HLX10 and HLX04 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and HLX04 and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
    Interventions:
    • Drug: HLX10, an engineered anti-PD-1 antibody
    • Drug: HLX04, a bevacizumab biosimilar
    • Drug: Carboplatin
    • Drug: Pemetrexed
  • Experimental: Part 2-Arm B (HLX10+Carboplatin+Pemetrexed)
    Participants will receive IV infusion of HLX10 on Day 1 of each 21-day cycle followed by IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion of HLX10 until loss of clinical benefit and Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
    Interventions:
    • Drug: HLX10, an engineered anti-PD-1 antibody
    • Drug: Carboplatin
    • Drug: Pemetrexed
  • Active Comparator: Part 2-Arm C (Carboplatin+Pemetrexed)
    Participants will receive IV infusion of Carboplatin and Pemetrexed on Day 1 of each 21-day cycle for 4 cycles or until loss of clinical benefit whichever occurs first, during induction treatment phase. Participants will receive IV infusion Pemetrexed until progressive disease, unacceptable toxicity, or death during maintenance treatment phase.
    Interventions:
    • Drug: Carboplatin
    • Drug: Pemetrexed
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: May 14, 2019)
636
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 22, 2022
Estimated Primary Completion Date June 24, 2022   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically or cytologically confirmed, Stage IIIB/IIIC or IV non-squamous NSCLC
  2. Participants with no EGFR, ALK and ROS1 mutation.
  3. Participants with no prior treatment for Stage IIIB/IIIC or IV non-squamous NSCLC
  4. Measurable disease as defined by RECIST v1.1
  5. Eastern Cooperative Oncology Group performance status 0 or 1
  6. Adequate hematologic and end organ function

Exclusion Criteria:

  1. Malignancies other than NSCLC within 5 years prior to randomization, with the exception of those with a negligible risk of metastasis or death treated with expected curative outcome
  2. Active central nervous system metastases
  3. Prior treatment with cluster of differentiation immune checkpoint blockade therapies or Bevacizumab
  4. Has received a surgical operation within 4 weeks from the initial drug administration
  5. Active or suspected autoimmune diseases. Subjects in a stable state with no need for systemic immunosuppressant therapy are allowed to enroll.
  6. Currently having or have had interstitial pneumonia, pneumoconiosis, radiation pneumonitis, drug-related pneumonitis and severe impaired pulmonary function that may interfere with the detection and management of suspected drug-related pulmonary toxicity
  7. Any active infection requiring systemic anti-infective therapy within 14 days prior to study drug administration
  8. Uncontrollable active infection(s)
  9. History of immunodeficiency, including HIV antibody positive
  10. active hepatitis B; or hepatitis C virus infections
  11. Has bleeding tendency
  12. History of severe cardiovascular diseases
  13. Known gastrointestinal diseases as follows, Gastrointestinal perforation, abdominal fistula or abdominal abscess within 6 months before signing the informed consent; History of poorly controlled or recurrent inflammatory bowel disease; Active peptic ulcers, or > moderate esophageal varices
  14. Pregnant or breastfeeding female
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Xia Zhang +86 150 6880 5856 Xia_Zhang@henlius.com
Contact: Peipei Zai +86 155 2206 7076 peipei_zhai@henlius.com
Listed Location Countries  ICMJE China
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03952403
Other Study ID Numbers  ICMJE HLX10-002-NSCLC301
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Shanghai Henlius Biotech
Study Sponsor  ICMJE Shanghai Henlius Biotech
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Yankai Shi, professor Cancer Hospital Chinese Academy of Medical Sciences (CAMS)
PRS Account Shanghai Henlius Biotech
Verification Date April 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP