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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)

NCT03952403

Description:

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).

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 3

Trial Eligibility

Document

Title

  • Brief Title: 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: 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 Metastatic Non-Squamous Non-Small Cell Lung Cancer (NSCLC)

Clinical Trial IDs

  • ORG STUDY ID: HLX10-002-NSCLC301
  • NCT ID: NCT03952403

Conditions

  • Carcinoma
  • Non-Small-Cell Lung

Interventions

DrugSynonymsArms
HLX10, an engineered anti-PD-1 antibodyPart 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed)
HLX04, a bevacizumab biosimilarPart 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed)
CarboplatinPart 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed)
PemetrexedPart 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed)

Purpose

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 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).

Trial Arms

NameTypeDescriptionInterventions
Part 1-Cohort 1 (HLX10+HLX04+Carboplatin+Pemetrexed)ExperimentalParticipants 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.
  • HLX10, an engineered anti-PD-1 antibody
  • HLX04, a bevacizumab biosimilar
  • Carboplatin
  • Pemetrexed
Part 2-Arm A (HLX10+HLX04+Carboplatin+Pemetrexed)ExperimentalParticipants 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.
  • HLX10, an engineered anti-PD-1 antibody
  • HLX04, a bevacizumab biosimilar
  • Carboplatin
  • Pemetrexed
Part 2-Arm B (HLX10+Carboplatin+Pemetrexed)ExperimentalParticipants 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.
  • HLX10, an engineered anti-PD-1 antibody
  • Carboplatin
  • Pemetrexed
Part 2-Arm C (Carboplatin+Pemetrexed)Active ComparatorParticipants 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.
  • Carboplatin
  • Pemetrexed

Eligibility Criteria

        Inclusion Criteria:

          1. Histologically or cytologically confirmed, Stage IV non-squamous NSCLC

          2. Participants with no EGFR, ALK and ROS1 mutation.

          3. Participants with no prior treatment for Stage 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
      
Maximum Eligible Age:75 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Number of participants with treatment-related adverse events as assessed by CTCAE v4.03
Time Frame:baseline to 21 days
Safety Issue:
Description:

Secondary Outcome Measures

Measure:Part 1 and 2-Incidence rates of AEs and SAEs
Time Frame:Baseline up to approximately 27months
Safety Issue:
Description:
Measure:Part 1 and 2-Overall Survival (OS)
Time Frame:Baseline until death (up to approximately 36 months)
Safety Issue:
Description:
Measure: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)
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure: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
Safety Issue:
Description:
Measure:Part 1 and 2-Pharmacokinetics (PK): serum HLX10 concentration
Time Frame:Baseline up to approximately 25 months
Safety Issue:
Description:
Measure:Part 1 and 2-Immunogenicity evaluation: positive anti-drug antibody (ADA) rate
Time Frame:Baseline up to approximately 25 months
Safety Issue:
Description:
Measure:Part 1 and 2-PD-L1 expression level
Time Frame:Baseline
Safety Issue:
Description:
Measure:Part 1 and 2-Microsatellite instability(MSI)
Time Frame:Baseline
Safety Issue:
Description:
Measure:Part 1 and 2-Tumor mutation burden(TMB)
Time Frame:Baseline
Safety Issue:
Description:
Measure:Part 1 and 2- Quality of life assessment
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description:EORTC QLQ-C30
Measure:Part 1 and 2- Quality of life assessment
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description:EQ-5D-5L
Measure:Part 1 and 2- Quality of life assessment
Time Frame:Baseline up to approximately 24 months
Safety Issue:
Description:EORTC QLQ-LC13

Details

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

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