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Study of Efficacy and Safety of Ociperlimab in Combination With Tislelizumab and Platinum-based Doublet Chemotherapy as First-line Treatment for Participants With Locally Advanced or Metastatic NSCLC. (AdvanTIG-306)

Primary Purpose

Non-small Cell Lung Cancer (NSCLC)

Status
Withdrawn
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Ociperlimab
Placebo
Tislelizumab
Pembrolizumab
Carboplatin
Cisplatin
Pemetrexed
Paclitaxel
Nab-paclitaxel
Sponsored by
Novartis Pharmaceuticals
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-small Cell Lung Cancer (NSCLC) focused on measuring AdvanTIG-306, ociperlimab, tislelizumab, pembrolizumab, carboplatin, cisplatin, paclitaxel, nab-paclitaxel, pemetrexed, squamous, non-squamous, non-small cell lung cancer, NSCLC, PD-L1

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Key Inclusion Criteria: Histologically confirmed locally advanced (stage IIIb/IIIc not eligible for definitive chemoradiation, radiation or surgery) or metastatic (stage IV) NSCLC (according to AJCC: Cancer Staging Manual, 8th edition) participants with no previous systemic treatment for advanced disease. Known PD-L1 status determined, prior to study randomization At least one measurable lesion as defined by RECIST 1.1 according to local radiology assessment at screening. ECOG performance status ≤1. Key Exclusion Criteria: Active autoimmune diseases requiring treatment with steroids or immunosuppressors in the past 2 years prior to randomization. History of severe hypersensitivity reaction or any contraindication to ociperlimab, tislelizumab, pembrolizumab (or any other monoclonal antibodies), platinum containing drugs, nab-paclitaxel, paclitaxel, pemetrexed or any known excipients of these drugs. Participants with known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with documented epidermal growth factor receptor (EGFR) sensitizing mutations, and/or ALK rearrangement assessed as part of the patients's standard of care by a validated test, as per local regulations will be excluded from the study. Participants with other known druggable molecular drivers (any histology) such as BRAF V600, KRASG12C, MET exon 14 mutations, NTRK, RET or ROS-1 rearrangement diagnosed per local tests who might be candidates for alternative targeted therapies as applicable per local regulations and treatment guidelines are excluded. Other inclusion/exclusion criteria may apply

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm 3

    Arm Type

    Experimental

    Active Comparator

    Placebo Comparator

    Arm Label

    Arm A: Ociperlimab + tislelizumab + chemotherapy

    Arm B: Placebo + pembrolizumab + chemotherapy

    Arm C: Placebo + tislelizumab + chemotherapy

    Arm Description

    Participants will receive ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy

    Participants will receive ociperlimab placebo in combination with pembrolizumab and platinum-based doublet chemotherapy

    Participants will receive ociperlimab placebo in combination with tislelizumab and platinum-based doublet chemotherapy

    Outcomes

    Primary Outcome Measures

    Progression-free survival (PFS) based on Blinded Independent Review Committee (BIRC) assessment as per RECIST 1.1 in participants with PD-L1 expression in ≥1% of tumor cells (Arm A and B)
    Time from date of randomization/start of treatment to the date of event defined as the first documented progression based on BIRC assessment as per RECIST 1.1 or death due to any cause in participants with PD-L1 expression in ≥1% of tumor cells, for participants in Arm A compared to Arm B
    Overall survival (OS) in participants with PD-L1 expression in ≥1% of tumor cells (Arm A and B)
    Time from date of randomization/start of treatment to date of death due to any cause in participants with PD-L1 expression in ≥1% of tumor cells, for participants in Arm A compared to Arm B

    Secondary Outcome Measures

    PFS based on BIRC assessment as per RECIST 1.1 in all participants regardless of PD-L1 status (Arm A and B)
    Time from date of randomization/start of treatment to the date of event defined as the first documented progression based on BIRC assessment as per RECIST 1.1 or death due to any cause in all participants in Arm A compared to Arm B
    OS in all participants regardless of PD-L1 status (Arm A and B)
    Time from date of randomization/start of treatment to date of death due to any cause in all participants in Arm A compared to Arm B.
    Overall response rate (ORR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)
    Percentage of participants with best overall response of complete response (CR) or partial response (PR) based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm B
    Disease Control Rate (DCR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)
    Percentage of participants with best overall response of CR, PR or stable disease (SD)based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm B
    Time to response (TTR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)
    Time from the date of randomization to the date of first documented response (CR or PR) based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm B
    Duration of response (DOR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)
    Time between the date of first documented response (CR or PR) and the date of first documented progression or death due to any cause based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm B
    ORR based in BIRC assessment as per RECIST 1.1 (Arm A and C)
    Percentage of participants with best overall response of complete response (CR) or partial response (PR) based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm C
    DCR based in BIRC assessment as per RECIST 1.1 (Arm A and C)
    Percentage of participants with best overall response of CR, PR or stable disease (SD)based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm C
    TTR based in BIRC assessment as per RECIST 1.1 (Arm A and C)
    Time from the date of randomization to the date of first documented response (CR or PR) based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm C
    DOR based in BIRC assessment as per RECIST 1.1 (Arm A and C)
    Time between the date of first documented response (CR or PR) and the date of first documented progression or death due to any cause based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm C
    PFS based on BIRC assessment as per RECIST 1.1 (Arm A and C)
    Time from date of randomization/start of treatment to the date of event defined as the first documented progression based on BIRC assessment as per RECIST 1.1 or death due to any cause in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm C
    Pharmacokinetic (PK) parameter: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of ociperlimab and tislelizumab
    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of ociperlimab and tislelizumab. AUClast will be summarized using descriptive statistics.
    PK parameter: Maximum concentration (Cmax) of ociperlimab and tislelizumab
    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of ociperlimab and tislelizumab. Cmax will be summarized using descriptive statistics.
    PK parameter: Time to reach maximum concentration (Tmax) of ociperlimab and tislelizumab
    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of ociperlimab and tislelizumab. Tmax will be summarized using descriptive statistics.
    PK parameter: Lowest serum concentration reached before the next dose is administered (Ctrough) of ociperlimab and tislelizumab
    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of ociperlimab and tislelizumab. Ctrough will be summarized using descriptive statistics.
    PK parameter: AUC calculated at the end of the dosing interval (AUCtau)of ociperlimab and tislelizumab
    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of ociperlimab and tislelizumab. AUCtau will be summarized using descriptive statistics.
    Immunogenicity: Anti-drug antibodies (ADA) prevalence at baseline of ociperlimab and tislelizumab
    Prevalence of ADA (anti-ociperlimab, anti-tislelizumab) at baseline is defined as the percentage of participants who have an ADA positive result at baseline
    Immunogenicity: ADA incidence following treatment with ociperlimab and tislelizumab
    Incidence of ADA (anti-ociperlimab, anti-tislelizumab) on treatment is defined as the percentage of participants who are treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
    Time to definitive 10-point deterioration in physical and role functioning on the EORTC QLQ-C30 questionnaire
    The EORTC QLQ-C30 is a questionnaire developed to assess the health-related quality of life of cancer participants. It assesses 15 domains consisting of 5 functional domains (physical, role, emotional, cognitive, social) and 9 symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and a global health status/quality of life (QoL) scale. All of the domain scores range from 0 to 100. A high score for a functional scale indicates a high and healthy level of functioning but a high score for a symptom scale indicates a high level of symptoms. The time to definitive 10 point deterioration of physical functioning and role functioning is defined as the time from the date of randomization to first onset of ≥10 points increase from baseline (worsening) of the corresponding scale score, with no later change below this threshold or death due to any cause.
    Time to definitive 10-point deterioration in symptom scores for chest pain, cough and dyspnea on the EORTC QLQ-LC13 questionnaire
    The Lung Cancer module of the EORTC's quality of life questionnaire (EORTC QLQ-LC13) is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The lung cancer module incorporates one multi-item scale to assess dyspnea, and 9 single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All of the domain scores range from 0 to 100. A high score indicates a high level of symptoms. The time to first 10 point deterioration symptom scores of chest pain, cough and dyspnea is defined as the time from the date of randomization to first onset of ≥10 points increase from baseline (worsening) of the corresponding scale score, with no later change below this threshold or death due to any cause.
    Time to confirmed 10-point deterioration in physical and role functioning on the EORTC QLQ-C30 questionnaire
    The EORTC QLQ-C30 is a questionnaire developed to assess the health-related quality of life of cancer participants. It assesses 15 domains consisting of 5 functional domains (physical, role, emotional, cognitive, social) and 9 symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and a global health status/quality of life (QoL) scale. All of the domain scores range from 0 to 100. A high score for a functional scale indicates a high and healthy level of functioning but a high score for a symptom scale indicates a high level of symptoms. The time to confirmed 10-point deterioration of physical functioning and role functioning is defined as the time from the date of randomization to first onset of≥10 points deterioration from baseline and confirmed by a second consecutive ≥10 points deterioration from baseline, or one assessment followed by death from any cause before the next scheduled data collection.
    Time to confirmed 10-point deterioration in symptom scores for chest pain, cough and dyspnea on the EORTC QLQ-LC13 questionnaire
    The Lung Cancer module of the EORTC's quality of life questionnaire (EORTC QLQ-LC13) is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The lung cancer module incorporates one multi-item scale to assess dyspnea, and 9 single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All of the domain scores range from 0 to 100. A high score indicates a high level of symptoms. The time to first 10 point deterioration symptom scores of chest pain, cough and dyspnea is defined as the time from the date of randomization to first onset of≥10 points deterioration from baseline and confirmed by a second consecutive ≥10 points deterioration from baseline, or one assessment followed by death from any cause before the next scheduled data collection.
    Time to definitive 10-point deterioration in global health status/quality of life, shortness of breath and pain on the EORTC QLQ-C30 questionnaire
    The EORTC QLQ-C30 is a questionnaire developed to assess the health-related quality of life of cancer participants. It assesses 15 domains consisting of 5 functional domains (physical, role, emotional, cognitive, social) and 9 symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and a global health status/quality of life (QoL) scale. All of the domain scores range from 0 to 100. A high score for a functional scale indicates a high and healthy level of functioning but a high score for a symptom scale indicates a high level of symptoms. The time to definitive 10-point deterioration in global health status/quality of life, shortness of breath and pain scores is defined as the time from the date of randomization to first onset of ≥10 points increase from baseline (worsening) of the corresponding scale score, with no later change below this threshold or death due to any cause.
    Utility scores of the EQ-5D-5L
    EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.
    Progression-free survival deferred (PFS2)
    Time from date of randomization to the first documented progression on next line therapy or death from any cause, whichever occurs first
    Time to definitive deterioration of the ECOG performance status
    Time to definitive deterioration of the ECOG PS by one category of the score. The ECOG PS is a measure of functional status. It ranges from 0 to 5, with 0 denoting perfect health and 5 death. A deterioration is considered definitive if no improvements in the ECOG PS status is observed at any subsequent time of measurement during the treatment period following the time point where the deterioration is observed.

    Full Information

    First Posted
    March 17, 2023
    Last Updated
    July 21, 2023
    Sponsor
    Novartis Pharmaceuticals
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    1. Study Identification

    Unique Protocol Identification Number
    NCT05791097
    Brief Title
    Study of Efficacy and Safety of Ociperlimab in Combination With Tislelizumab and Platinum-based Doublet Chemotherapy as First-line Treatment for Participants With Locally Advanced or Metastatic NSCLC.
    Acronym
    AdvanTIG-306
    Official Title
    AdvanTIG-306: A Randomized, Double-blind, Placebo-controlled, Phase III Study Evaluating the Efficacy and Safety of Ociperlimab (WCD118/BGB-A1217) Combined With Tislelizumab (VDT482/BGB-A317) Plus Platinum-based Doublet Chemotherapy Versus Placebo Combined With Pembrolizumab Plus Platinum-based Doublet Chemotherapy as First-line Therapy for Participants With Locally Advanced or Metastatic Non-small Cell Lung Cancer (NSCLC)
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    July 2023
    Overall Recruitment Status
    Withdrawn
    Why Stopped
    Business decision, not driven by safety concerns; no new safety signals have been observed in the ociperlimab program.
    Study Start Date
    July 28, 2023 (Anticipated)
    Primary Completion Date
    December 24, 2027 (Anticipated)
    Study Completion Date
    December 26, 2027 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Novartis Pharmaceuticals

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    Yes
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    Yes

    5. Study Description

    Brief Summary
    The primary scientific question of interest is whether the addition of ociperlimab to platinum-based chemotherapy and tislelizumab improve progression-free survival (PFS) or overall survival (OS) compared to pembrolizumab and platinum-based chemotherapy as first-line therapy for participants with locally advanced or metastatic squamous or non-squamous NSCLC with PD-L1 expression of ≥1%.
    Detailed Description
    This is a randomized, double-blind, placebo controlled, multicenter, phase III study evaluating the efficacy and safety of ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy as first-line treatment for participants with locally advanced or metastatic NSCLC without actionable driver mutations. Participants will receive study treatment every three weeks and will continue to receive it until RECIST 1.1 disease progression as determined by Investigator and confirmed by BIRC, unacceptable toxicity that precludes further treatment, treatment is discontinued at the discretion of the Investigator or participant, participant withdrawal of consent, pregnancy, lost to follow-up, or death.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Non-small Cell Lung Cancer (NSCLC)
    Keywords
    AdvanTIG-306, ociperlimab, tislelizumab, pembrolizumab, carboplatin, cisplatin, paclitaxel, nab-paclitaxel, pemetrexed, squamous, non-squamous, non-small cell lung cancer, NSCLC, PD-L1

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    ParticipantCare ProviderInvestigatorOutcomes Assessor
    Allocation
    Randomized
    Enrollment
    0 (Actual)

    8. Arms, Groups, and Interventions

    Arm Title
    Arm A: Ociperlimab + tislelizumab + chemotherapy
    Arm Type
    Experimental
    Arm Description
    Participants will receive ociperlimab in combination with tislelizumab and platinum-based doublet chemotherapy
    Arm Title
    Arm B: Placebo + pembrolizumab + chemotherapy
    Arm Type
    Active Comparator
    Arm Description
    Participants will receive ociperlimab placebo in combination with pembrolizumab and platinum-based doublet chemotherapy
    Arm Title
    Arm C: Placebo + tislelizumab + chemotherapy
    Arm Type
    Placebo Comparator
    Arm Description
    Participants will receive ociperlimab placebo in combination with tislelizumab and platinum-based doublet chemotherapy
    Intervention Type
    Drug
    Intervention Name(s)
    Ociperlimab
    Other Intervention Name(s)
    WCD118
    Intervention Description
    Ociperlimab is a monoclonal antibody formulated for intravenous infusion. 900 mg of ociperlimab will be administered on Day 1 of each 21-day cycle
    Intervention Type
    Drug
    Intervention Name(s)
    Placebo
    Intervention Description
    Placebo infusions will consist of a sterile, normal saline solution. Placebo will be administered on Day 1 of each 21-day cycle
    Intervention Type
    Drug
    Intervention Name(s)
    Tislelizumab
    Other Intervention Name(s)
    VDT482
    Intervention Description
    Tislelizumab is a monoclonal antibody formulated for intravenous infusion. 200 mg of tislelizumab will be administered on Day 1 of each 21-day cycle
    Intervention Type
    Drug
    Intervention Name(s)
    Pembrolizumab
    Intervention Description
    Pembrolizumab is a monoclonal antibody formulated for intravenous infusion. 200 mg of pembrolizumab will be administered on Day 1 of each 21-day cycle
    Intervention Type
    Drug
    Intervention Name(s)
    Carboplatin
    Intervention Description
    Carboplatin is a chemotherapy agent formulated for intravenous infusion. Carboplatin will be administered (AUC 6 mg/mL*min) on Day 1 of each 21-day cycle
    Intervention Type
    Drug
    Intervention Name(s)
    Cisplatin
    Intervention Description
    Cisplatin is a chemotherapy agent formulated for intravenous infusion. Cisplatin will be administered (75 mg/m^2) on Day 1 of each 21-day cycle
    Intervention Type
    Drug
    Intervention Name(s)
    Pemetrexed
    Intervention Description
    Pemetrexed is a chemotherapy agent formulated for intravenous infusion. Pemetrexed will be administered (500 mg/m^2) on Day 1 of each 21-day cycle
    Intervention Type
    Drug
    Intervention Name(s)
    Paclitaxel
    Intervention Description
    Paclitaxel is a chemotherapy agent formulated for intravenous infusion. Paclitaxel will be administered (200 mg/m^2) on Day 1 of each 21-day cycle
    Intervention Type
    Drug
    Intervention Name(s)
    Nab-paclitaxel
    Intervention Description
    Nab-paclitaxel is a chemotherapy agent formulated for intravenous infusion. Nab-paclitaxel will be administered (100 mg/m^2) on Day 1, 8 and 15 of each 21-day cycle
    Primary Outcome Measure Information:
    Title
    Progression-free survival (PFS) based on Blinded Independent Review Committee (BIRC) assessment as per RECIST 1.1 in participants with PD-L1 expression in ≥1% of tumor cells (Arm A and B)
    Description
    Time from date of randomization/start of treatment to the date of event defined as the first documented progression based on BIRC assessment as per RECIST 1.1 or death due to any cause in participants with PD-L1 expression in ≥1% of tumor cells, for participants in Arm A compared to Arm B
    Time Frame
    Up to 30 months
    Title
    Overall survival (OS) in participants with PD-L1 expression in ≥1% of tumor cells (Arm A and B)
    Description
    Time from date of randomization/start of treatment to date of death due to any cause in participants with PD-L1 expression in ≥1% of tumor cells, for participants in Arm A compared to Arm B
    Time Frame
    Up to 52 months
    Secondary Outcome Measure Information:
    Title
    PFS based on BIRC assessment as per RECIST 1.1 in all participants regardless of PD-L1 status (Arm A and B)
    Description
    Time from date of randomization/start of treatment to the date of event defined as the first documented progression based on BIRC assessment as per RECIST 1.1 or death due to any cause in all participants in Arm A compared to Arm B
    Time Frame
    Up to 30 months
    Title
    OS in all participants regardless of PD-L1 status (Arm A and B)
    Description
    Time from date of randomization/start of treatment to date of death due to any cause in all participants in Arm A compared to Arm B.
    Time Frame
    Up to 52 months
    Title
    Overall response rate (ORR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)
    Description
    Percentage of participants with best overall response of complete response (CR) or partial response (PR) based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm B
    Time Frame
    Up to 30 months
    Title
    Disease Control Rate (DCR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)
    Description
    Percentage of participants with best overall response of CR, PR or stable disease (SD)based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm B
    Time Frame
    Up to 30 months
    Title
    Time to response (TTR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)
    Description
    Time from the date of randomization to the date of first documented response (CR or PR) based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm B
    Time Frame
    Up to 30 months
    Title
    Duration of response (DOR) based in BIRC assessment as per RECIST 1.1 (Arm A and B)
    Description
    Time between the date of first documented response (CR or PR) and the date of first documented progression or death due to any cause based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm B
    Time Frame
    Up to 30 months
    Title
    ORR based in BIRC assessment as per RECIST 1.1 (Arm A and C)
    Description
    Percentage of participants with best overall response of complete response (CR) or partial response (PR) based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm C
    Time Frame
    Up to 30 months
    Title
    DCR based in BIRC assessment as per RECIST 1.1 (Arm A and C)
    Description
    Percentage of participants with best overall response of CR, PR or stable disease (SD)based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm C
    Time Frame
    Up to 30 months
    Title
    TTR based in BIRC assessment as per RECIST 1.1 (Arm A and C)
    Description
    Time from the date of randomization to the date of first documented response (CR or PR) based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm C
    Time Frame
    Up to 30 months
    Title
    DOR based in BIRC assessment as per RECIST 1.1 (Arm A and C)
    Description
    Time between the date of first documented response (CR or PR) and the date of first documented progression or death due to any cause based in BIRC assessment as per RECIST 1.1 in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm C
    Time Frame
    Up to 30 months
    Title
    PFS based on BIRC assessment as per RECIST 1.1 (Arm A and C)
    Description
    Time from date of randomization/start of treatment to the date of event defined as the first documented progression based on BIRC assessment as per RECIST 1.1 or death due to any cause in participants with PD-L1 expression ≥1% and in all participants randomized, for participants in Arm A compared to Arm C
    Time Frame
    Up to 30 months
    Title
    Pharmacokinetic (PK) parameter: Area under the serum concentration-time curve from time zero to the time of last quantifiable concentration (AUClast) of ociperlimab and tislelizumab
    Description
    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of ociperlimab and tislelizumab. AUClast will be summarized using descriptive statistics.
    Time Frame
    Up to 30 months
    Title
    PK parameter: Maximum concentration (Cmax) of ociperlimab and tislelizumab
    Description
    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of ociperlimab and tislelizumab. Cmax will be summarized using descriptive statistics.
    Time Frame
    Up to 30 months
    Title
    PK parameter: Time to reach maximum concentration (Tmax) of ociperlimab and tislelizumab
    Description
    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of ociperlimab and tislelizumab. Tmax will be summarized using descriptive statistics.
    Time Frame
    Up to 30 months
    Title
    PK parameter: Lowest serum concentration reached before the next dose is administered (Ctrough) of ociperlimab and tislelizumab
    Description
    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of ociperlimab and tislelizumab. Ctrough will be summarized using descriptive statistics.
    Time Frame
    Up to 30 months
    Title
    PK parameter: AUC calculated at the end of the dosing interval (AUCtau)of ociperlimab and tislelizumab
    Description
    Venous whole blood samples will be collected for activity-based pharmacokinetics characterization of ociperlimab and tislelizumab. AUCtau will be summarized using descriptive statistics.
    Time Frame
    Up to 30 months
    Title
    Immunogenicity: Anti-drug antibodies (ADA) prevalence at baseline of ociperlimab and tislelizumab
    Description
    Prevalence of ADA (anti-ociperlimab, anti-tislelizumab) at baseline is defined as the percentage of participants who have an ADA positive result at baseline
    Time Frame
    Baseline
    Title
    Immunogenicity: ADA incidence following treatment with ociperlimab and tislelizumab
    Description
    Incidence of ADA (anti-ociperlimab, anti-tislelizumab) on treatment is defined as the percentage of participants who are treatment-induced ADA positive (post-baseline ADA positive with ADA-negative sample at baseline) and treatment-boosted ADA positive (post-baseline ADA positive with titer that is at least the fold titer change greater than the ADA-positive baseline titer)
    Time Frame
    Up to 30 months
    Title
    Time to definitive 10-point deterioration in physical and role functioning on the EORTC QLQ-C30 questionnaire
    Description
    The EORTC QLQ-C30 is a questionnaire developed to assess the health-related quality of life of cancer participants. It assesses 15 domains consisting of 5 functional domains (physical, role, emotional, cognitive, social) and 9 symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and a global health status/quality of life (QoL) scale. All of the domain scores range from 0 to 100. A high score for a functional scale indicates a high and healthy level of functioning but a high score for a symptom scale indicates a high level of symptoms. The time to definitive 10 point deterioration of physical functioning and role functioning is defined as the time from the date of randomization to first onset of ≥10 points increase from baseline (worsening) of the corresponding scale score, with no later change below this threshold or death due to any cause.
    Time Frame
    Up to 30 months
    Title
    Time to definitive 10-point deterioration in symptom scores for chest pain, cough and dyspnea on the EORTC QLQ-LC13 questionnaire
    Description
    The Lung Cancer module of the EORTC's quality of life questionnaire (EORTC QLQ-LC13) is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The lung cancer module incorporates one multi-item scale to assess dyspnea, and 9 single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All of the domain scores range from 0 to 100. A high score indicates a high level of symptoms. The time to first 10 point deterioration symptom scores of chest pain, cough and dyspnea is defined as the time from the date of randomization to first onset of ≥10 points increase from baseline (worsening) of the corresponding scale score, with no later change below this threshold or death due to any cause.
    Time Frame
    Up to 30 months
    Title
    Time to confirmed 10-point deterioration in physical and role functioning on the EORTC QLQ-C30 questionnaire
    Description
    The EORTC QLQ-C30 is a questionnaire developed to assess the health-related quality of life of cancer participants. It assesses 15 domains consisting of 5 functional domains (physical, role, emotional, cognitive, social) and 9 symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and a global health status/quality of life (QoL) scale. All of the domain scores range from 0 to 100. A high score for a functional scale indicates a high and healthy level of functioning but a high score for a symptom scale indicates a high level of symptoms. The time to confirmed 10-point deterioration of physical functioning and role functioning is defined as the time from the date of randomization to first onset of≥10 points deterioration from baseline and confirmed by a second consecutive ≥10 points deterioration from baseline, or one assessment followed by death from any cause before the next scheduled data collection.
    Time Frame
    Up to 30 months
    Title
    Time to confirmed 10-point deterioration in symptom scores for chest pain, cough and dyspnea on the EORTC QLQ-LC13 questionnaire
    Description
    The Lung Cancer module of the EORTC's quality of life questionnaire (EORTC QLQ-LC13) is used in conjunction with the EORTC QLQ-C30 and provides information on an additional 13 items specifically related to lung cancer. The lung cancer module incorporates one multi-item scale to assess dyspnea, and 9 single items assessing pain, coughing, sore mouth, dysphagia, peripheral neuropathy, alopecia, and hemoptysis. All of the domain scores range from 0 to 100. A high score indicates a high level of symptoms. The time to first 10 point deterioration symptom scores of chest pain, cough and dyspnea is defined as the time from the date of randomization to first onset of≥10 points deterioration from baseline and confirmed by a second consecutive ≥10 points deterioration from baseline, or one assessment followed by death from any cause before the next scheduled data collection.
    Time Frame
    Up to 30 months
    Title
    Time to definitive 10-point deterioration in global health status/quality of life, shortness of breath and pain on the EORTC QLQ-C30 questionnaire
    Description
    The EORTC QLQ-C30 is a questionnaire developed to assess the health-related quality of life of cancer participants. It assesses 15 domains consisting of 5 functional domains (physical, role, emotional, cognitive, social) and 9 symptom domains (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties) and a global health status/quality of life (QoL) scale. All of the domain scores range from 0 to 100. A high score for a functional scale indicates a high and healthy level of functioning but a high score for a symptom scale indicates a high level of symptoms. The time to definitive 10-point deterioration in global health status/quality of life, shortness of breath and pain scores is defined as the time from the date of randomization to first onset of ≥10 points increase from baseline (worsening) of the corresponding scale score, with no later change below this threshold or death due to any cause.
    Time Frame
    Up to 30 months
    Title
    Utility scores of the EQ-5D-5L
    Description
    EQ-5D-5L is a standardized participant completed questionnaire that measures health-related quality of life and translates that score into an index value or utility score. EQ-5D-5L consists of two components: a health state profile and an optional visual analogue scale (VAS). EQ-5D health state profile is comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has 5 levels: 1= no problems, 2= slight problems, 3= moderate problems, 4= severe problems, and 5= extreme problems. Higher scores indicated greater levels of problems across each of the five dimensions.
    Time Frame
    Up to 30 months
    Title
    Progression-free survival deferred (PFS2)
    Description
    Time from date of randomization to the first documented progression on next line therapy or death from any cause, whichever occurs first
    Time Frame
    Up to 30 months
    Title
    Time to definitive deterioration of the ECOG performance status
    Description
    Time to definitive deterioration of the ECOG PS by one category of the score. The ECOG PS is a measure of functional status. It ranges from 0 to 5, with 0 denoting perfect health and 5 death. A deterioration is considered definitive if no improvements in the ECOG PS status is observed at any subsequent time of measurement during the treatment period following the time point where the deterioration is observed.
    Time Frame
    Up to 30 months

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Key Inclusion Criteria: Histologically confirmed locally advanced (stage IIIb/IIIc not eligible for definitive chemoradiation, radiation or surgery) or metastatic (stage IV) NSCLC (according to AJCC: Cancer Staging Manual, 8th edition) participants with no previous systemic treatment for advanced disease. Known PD-L1 status determined, prior to study randomization At least one measurable lesion as defined by RECIST 1.1 according to local radiology assessment at screening. ECOG performance status ≤1. Key Exclusion Criteria: Active autoimmune diseases requiring treatment with steroids or immunosuppressors in the past 2 years prior to randomization. History of severe hypersensitivity reaction or any contraindication to ociperlimab, tislelizumab, pembrolizumab (or any other monoclonal antibodies), platinum containing drugs, nab-paclitaxel, paclitaxel, pemetrexed or any known excipients of these drugs. Participants with known active central nervous system (CNS) metastases and/or carcinomatous meningitis. Participants with documented epidermal growth factor receptor (EGFR) sensitizing mutations, and/or ALK rearrangement assessed as part of the patients's standard of care by a validated test, as per local regulations will be excluded from the study. Participants with other known druggable molecular drivers (any histology) such as BRAF V600, KRASG12C, MET exon 14 mutations, NTRK, RET or ROS-1 rearrangement diagnosed per local tests who might be candidates for alternative targeted therapies as applicable per local regulations and treatment guidelines are excluded. Other inclusion/exclusion criteria may apply
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Novartis Pharmaceuticals
    Organizational Affiliation
    Novartis Pharmaceuticals
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Plan to Share IPD
    Yes
    IPD Sharing Plan Description
    Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations. This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com

    Learn more about this trial

    Study of Efficacy and Safety of Ociperlimab in Combination With Tislelizumab and Platinum-based Doublet Chemotherapy as First-line Treatment for Participants With Locally Advanced or Metastatic NSCLC.

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