Clinical Trials /

Phase II Platform Trial of Novel Regimens Versus Standard of Care (SoC) in Non-small Cell Lung Cancer (NSCLC)

NCT03739710

Description:

This study will compare the clinical activity of novel immune-oncology agents (in combination or as single agents) to standard of care in participants with relapsed/refractory advanced NSCLC. The study will initially evaluate two treatment regimens/arms. Additional regimens/arms may be added via future protocol amendment(s). Participants will be stratified by histology (squamous vs. non-squamous) and line of anti-programmed cell death ligand 1 (PD[L]1) therapy (first vs. second line). Initially, the study will evaluate the GSK3359609 inducible T-cell co-stimulator (ICOS) agonist in combination with SoC docetaxel compared to docetaxel alone (sub-study 1). SoC arm will be the common comparison arm across all sub-studies. At study start, subjects will be randomized to the study at a ratio of 1:2 to Arm 1 (docetaxel) and Arm 2 (ICOS agonist + docetaxel). The study will consist of three periods: Screening, Treatment, and Follow-Up. There will be approximately 105 participants enrolled in the study initially. Treatment will continue for approximately 2 years and participants will be followed for survival during the follow-up period.

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

Recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Phase II Platform Trial of Novel Regimens Versus Standard of Care (SoC) in Non-small Cell Lung Cancer (NSCLC)
  • Official Title: A Phase II, Randomized, Open-label Platform Trial Utilizing a Master Protocol to Study Novel Regimens Versus Standard of Care Treatment in NSCLC Participants

Clinical Trial IDs

  • ORG STUDY ID: 205801
  • NCT ID: NCT03739710

Conditions

  • Neoplasms

Interventions

DrugSynonymsArms
DocetaxelSubjects receiving GSK3359609 (ICOS Agonist) + Docetaxel
GSK3359609 (ICOS Agonist)Subjects receiving GSK3359609 (ICOS Agonist) + Docetaxel

Purpose

This study will compare the clinical activity of novel immune-oncology agents (in combination or as single agents) to standard of care in participants with relapsed/refractory advanced NSCLC. The study will initially evaluate two treatment regimens/arms. Additional regimens/arms may be added via future protocol amendment(s). Participants will be stratified by histology (squamous vs. non-squamous) and line of anti-programmed cell death ligand 1 (PD[L]1) therapy (first vs. second line). Initially, the study will evaluate the GSK3359609 inducible T-cell co-stimulator (ICOS) agonist in combination with SoC docetaxel compared to docetaxel alone (sub-study 1). SoC arm will be the common comparison arm across all sub-studies. At study start, subjects will be randomized to the study at a ratio of 1:2 to Arm 1 (docetaxel) and Arm 2 (ICOS agonist + docetaxel). The study will consist of three periods: Screening, Treatment, and Follow-Up. There will be approximately 105 participants enrolled in the study initially. Treatment will continue for approximately 2 years and participants will be followed for survival during the follow-up period.

Trial Arms

NameTypeDescriptionInterventions
Subjects receiving GSK3359609 (ICOS Agonist) + DocetaxelExperimentalSubjects will receive the combination once every 3 weeks as an IV infusion. Subjects receiving docetaxel will be premedicated according to approved product label or standard practice.
  • Docetaxel
  • GSK3359609 (ICOS Agonist)
Subjects receiving DocetaxelActive ComparatorSubjects will receive docetaxel once in every 3 weeks as an intravenous infusion.
  • Docetaxel

Eligibility Criteria

        Inclusion Criteria:

          -  Subjects capable of giving signed informed consent/assent.

          -  Male or female, aged 18 years or older at the time consent is obtained. Subjects in
             Korea must be age 19 years or older at the time consent is obtained.

          -  Subjects with histologically or cytologically confirmed diagnosis of NSCLC (squamous
             or nonsquamous) and: a. Documented disease progression based on radiographic imaging,
             during or after a maximum of 2 lines of systemic treatment for locally/regionally
             advanced recurrent, Stage IIIb/Stage IV or metastatic disease. Two components of
             treatment must have been received in the same line or as separate lines of therapy: i.
             A maximum of 1 line of platinum-containing chemotherapy regimen in the metastatic
             setting, and ii. A maximum of 1 line of PD(L)1 mAb containing regimen. b. Subjects
             with known BRAF molecular alterations must have had disease progression after
             receiving the locally available SoC treatment for the molecular alteration.

          -  Measurable disease, presenting with at least 1 measurable lesion per RECIST 1.1.

          -  ECOG PS score of 0 or 1.

          -  A tumor tissue sample obtained at any time from the initial diagnosis of NSCLC to time
             of study entry is mandatory. Although a fresh tumor tissue sample obtained during
             screening is preferred, archival tumor specimen is acceptable.

          -  Adequate organ function.

          -  A male subject must agree to use a highly effective contraception during the treatment
             period and for at least 120 days after the last dose of study treatment and refrain
             from donating sperm during this period.

          -  A female subject is eligible to participate if she is not pregnant, not breastfeeding,
             and at least 1 of the following conditions apply: a) Not a woman of childbearing
             potential (WOCBP) or A WOCBP who agrees to follow the contraceptive guidance during
             the treatment period and for at least 120 days after the last dose of study treatment.

        Exclusion Criteria:

          -  Subjects who received prior treatment with the following therapies (calculation is
             based on date of last therapy to date of first dose of study treatment): a. Docetaxel
             at any time. b. Any of the investigational agents being tested in the current study,
             including experimental ICOS agonist. c. Systemic approved or investigational
             anticancer therapy within 30 days or 5 half-lives of the drug, whichever is shorter.
             At least 14 days must have elapsed between the last dose of prior anticancer agent and
             the first dose of study drug is administered. d. Prior radiation therapy: permissible
             if at least one non-irradiated measurable lesion is available for assessment per
             RECIST version 1.1 or if a solitary measurable lesion was irradiated, objective
             progression is documented. A wash out of at least 2 weeks before start of study drug
             for radiation of any intended use is required.

          -  Received >2 prior lines of therapy for NSCLC, including subjects with BRAF molecular
             alternations. Subjects with known EGFR/ALK/ROS1 molecular alterations are excluded
             from participation in this study however subjects with known exon 20 EGFR molecular
             alteration may be considered for inclusion in this study, if no other therapeutic
             options are available locally.

          -  Invasive malignancy or history of invasive malignancy other than disease under study
             within the last 2 years.

          -  Central nervous system (CNS) metastases, with the following exception: Subjects with
             asymptomatic CNS metastases who are clinically stable and have no requirement for
             steroids for at least 14 days prior to first dose of study treatment.

          -  Major surgery <= 28 days of first dose of study treatment.

          -  Autoimmune disease (current or history) or syndrome that required systemic treatment
             within the past 2 years. Replacement therapies which include physiological doses of
             corticosteroids for treatment of endocrinopathies (for example, adrenal insufficiency)
             are not considered systemic treatments. Subjects with controlled Type 1 diabetes
             mellitus (T1DM) are eligible.

          -  Receiving systemic steroids (>10 milligram [mg] oral prednisone or equivalent) or
             other immunosuppressive agents within 7 days prior to first dose of study treatment.

          -  Prior allogeneic/autologous bone marrow or solid organ transplantation.

          -  Receipt of any live vaccine within 30 days prior to first dose of study treatment.

          -  Toxicity from previous anticancer treatment that includes: a. >= Grade 3 toxicity
             considered related to prior immunotherapy and that led to treatment discontinuation.
             b. Toxicity related to prior treatment that has not resolved to <= Grade 1 (except
             alopecia, hearing loss, endocrinopathy managed with replacement therapy, and
             peripheral neuropathy which must be <= Grade 2).

          -  History (current and past) of idiopathic pulmonary fibrosis, pneumonitis (for
             past-pneumonitis exclusion only if steroids were required for treatment), interstitial
             lung disease, or organizing pneumonia.

          -  Recent history (within the past 6 months) of uncontrolled symptomatic ascites, pleural
             or pericardial effusions.

          -  Recent history (within the past 6 months) of gastrointestinal obstruction that
             required surgery, acute diverticulitis, inflammatory bowel disease, or intra-abdominal
             abscess.

          -  History or evidence of cardiac abnormalities within the 6 months prior to enrollment.

          -  Current unstable liver or biliary disease per investigator assessment defined by the
             presence of ascites, encephalopathy, coagulopathy, hypo-albuminemia, esophageal or
             gastric varices, persistent jaundice, or cirrhosis.

          -  Active infection requiring systemic therapy.

          -  Subjects with known human immunodeficiency virus infection.

          -  Subjects with history of severe hypersensitivity to monoclonal antibodies or
             hypersensitivity to ingredients used in the formulation of docetaxel.

          -  Subjects requiring ongoing therapy with a medication that is a strong inhibitor or
             inducer of the cytochrome 3A4 (CYP3A4) enzymes.

          -  Any serious and/or unstable pre-existing medical (aside from malignancy), psychiatric
             disorder, or other condition that could interfere with participant's safety, obtaining
             informed consent, or compliance to the study procedures in the opinion of the
             investigator.

          -  Pregnant or lactating female subjects.

          -  Subject is currently participating in or has participated in a study of an
             investigational device within 4 weeks prior to the first dose of study treatment.

          -  Subjects with presence of hepatitis B surface antigen (HBsAg) at screening or within 3
             months prior to first dose of study intervention.

          -  Subjects with positive hepatitis C antibody test result at screening or within 3
             months prior to first dose of study intervention. Subjects with positive Hepatitis C
             antibody due to prior resolved disease can be enrolled, only if a confirmatory
             negative Hepatitis C RNA test is obtained.

          -  Subjects with positive hepatitis C RNA test result at screening or within 3 months
             prior to first dose of study treatment. Test is optional and subjects with negative
             Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Time of overall survival
Time Frame:Up to 106 Weeks
Safety Issue:
Description:Overall survival time of subjects from randomization to death will be evaluated.

Secondary Outcome Measures

Measure:Survival rate at 12 months
Time Frame:Up to 12 months
Safety Issue:
Description:Milestone survival rate of participants treated with experimental regimens versus SoC therapy.
Measure:Survival rate at 18 months
Time Frame:Up to 18 months
Safety Issue:
Description:Milestone survival rate of participants treated with experimental regimens versus SoC therapy.
Measure:Number of participants with Complete response (CR)
Time Frame:Up to 4 years
Safety Issue:
Description:Number of participants with CR as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.
Measure:Number of participants with Partial response (PR)
Time Frame:Up to 4 years
Safety Issue:
Description:Number of participants with PR as per RECIST version 1.1 criteria.
Measure:Number of participants with Stable disease (SD)
Time Frame:Up to 4 years
Safety Issue:
Description:Number of participants with SD as per RECIST version 1.1 criteria.
Measure:Number of participants with Progressive disease (PD)
Time Frame:Up to 4 years
Safety Issue:
Description:Number of participants with PD as per RECIST version 1.1 criteria.
Measure:Progression-free survival (PFS)
Time Frame:Up to 4 years
Safety Issue:
Description:PFS is defined as time from the date of randomization to the date of disease progression or death whichever occurs earlier.
Measure:Overall response rate (ORR)
Time Frame:Up to 4 years
Safety Issue:
Description:ORR is defined as the percentage of participants with a confirmed CR or PR at any time per RECIST version 1.1 criteria.
Measure:Duration of response (DOR)
Time Frame:Up to 4 years
Safety Issue:
Description:DOR is defined as the first documented evidence of CR or PR until disease progression or death, per RECIST 1.1 criteria.
Measure:Number of participants with iCR
Time Frame:Up to 4 years
Safety Issue:
Description:Number of participants with iCR per modified RECIST 1.1 for immune-based therapeutics (iRECIST) criteria.
Measure:Number of participants with iPR
Time Frame:Up to 4 years
Safety Issue:
Description:Number of participants with iPR per iRECIST criteria.
Measure:Number of participants with unconfirmed progressive disease (iUPD)
Time Frame:Up to 4 years
Safety Issue:
Description:Number of participants with iUPD per iRECIST criteria.
Measure:Number of participants with confirmed progressive disease (iCPD)
Time Frame:Up to 4 years
Safety Issue:
Description:Number of participants with iCPD per iRECIST criteria.
Measure:Number of participants with iSD
Time Frame:Up to 4 years
Safety Issue:
Description:Number of participants with iSD per iRECIST criteria.
Measure:Progression-free survival (iPFS)
Time Frame:Up to 4 years
Safety Issue:
Description:PFS is defined as time from the date of randomization to the date of disease progression or death, whichever occurs earlier, per iRECIST criteria.
Measure:Overall response rate (iORR)
Time Frame:Up to 4 years
Safety Issue:
Description:ORR is defined as the percentage of participants with a confirmed CR or PR at any time per iRECIST criteria.
Measure:Duration of response (iDOR)
Time Frame:Up to 4 years
Safety Issue:
Description:iDOR is defined as the first documented evidence of CR or PR until disease progression or death, per iRECIST criteria.
Measure:Number of participants with adverse events (AE)
Time Frame:Up to 2 years
Safety Issue:
Description:An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment.
Measure:Number of participants with Adverse events of special interest (AESI)
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with AESI will be recorded for safety assessment. AESI are defined as events of potential immunologic etiology, including Immune-Related Adverse Events (irAEs).
Measure:Number of participants with Serious adverse events (SAE)
Time Frame:Up to 2 years
Safety Issue:
Description:A SAE is defined as any untoward occurrence that will lead to death or is life-threatening, or requires hospitalization or prolongation of existing hospitalization or results in persistent disability/incapacity or any congenital anomaly/birth defect.
Measure:Number of participants with AEs or SAEs leading to dose modification
Time Frame:Up to 2 years
Safety Issue:
Description:Participants who underwent dose modification due to AEs or SAEs will be recorded.
Measure:Number of participants with AEs or SAEs leading to dose delays
Time Frame:Up to 2 years
Safety Issue:
Description:Participants will have dose delays due to AEs or SAEs will be recorded.
Measure:Number of participants with AEs or SAEs leading to withdrawals
Time Frame:Up to 2 years
Safety Issue:
Description:Participants who withdrew from the study due to AEs or SAEs will be recorded.
Measure:Change from Baseline in temperature
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Temperature will be measured after 5 minutes of rest.
Measure:Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP)
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Blood pressure both systolic and diastolic will be measured after 5 minutes of rest.
Measure:Change from Baseline in pulse rate
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Pulse rate will be measured after 5 minutes of rest.
Measure:Change from Baseline in respiratory rate
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Respiratory rate will be measured after 5 minutes of rest.
Measure:Change from Baseline in oxygen saturation
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Oxygen saturation will be measured after 5 minutes of rest.
Measure:Change from Baseline of hematology parameters: eosinophils, lymphocytes, monocytes, basophils, neutrophils, platelet and leukocytes
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameters such as eosinophils, lymphocytes, monocytes, basophils, neutrophils, platelet and leukocytes will be evaluated.
Measure:Change from Baseline of hematology parameters: hematocrit
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameter such as hematocrit will be evaluated.
Measure:Change from Baseline of hematology parameter: hemoglobin
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameter such as hemoglobin will be evaluated.
Measure:Change from Baseline of hematology parameter: mean corpuscular hemoglobin
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameter such as mean corpuscular hemoglobin will be evaluated.
Measure:Change from Baseline of hematology parameter: mean corpuscular volume
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameter such as mean corpuscular volume will be evaluated.
Measure:Change from Baseline in hematology parameter: Red blood cell (RBC) count
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameter such as RBC count will be evaluated.
Measure:Change from Baseline of Clinical chemistry parameters: glucose, sodium, Blood Urea Nitrogen (BUN), calcium, and potassium
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameters such as glucose, sodium, BUN, calcium, and potassium will be evaluated.
Measure:Change from Baseline of Clinical chemistry parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST)
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameters such as alkaline phosphatase, ALT, and AST will be evaluated.
Measure:Change from Baseline of Clinical chemistry parameters: Direct bilirubin, Bilirubin, Creatinine.
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameters such as direct bilirubin, bilirubin, and creatinine will be evaluated.
Measure:Change from Baseline of Clinical chemistry parameters: lactate dehydrogenase (LDH)
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameter such as LDH will be evaluated.
Measure:Change from Baseline of Clinical chemistry parameters: Total protein and albumin
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameters such as total protein and albumin will be evaluated.
Measure:Change from Baseline in urinalysis parameters: ketones
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameter such as ketones will be evaluated.
Measure:Change from Baseline in Urinalysis parameter: Specific gravity
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameter such as specific gravity will be evaluated.
Measure:Change from Baseline in Urinalysis parameter: pH
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameter such as pH will be evaluated.
Measure:Change from Baseline in Urinalysis parameter: glucose
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameter such as glucose will be evaluated.
Measure:Change from Baseline in Urinalysis parameter: protein
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Change from Baseline for parameter such as protein will be evaluated.
Measure:Change from Baseline in Eastern Cooperative Oncology Group (ECOG) performance status (PS) score
Time Frame:Baseline and up to 106 Weeks
Safety Issue:
Description:Performance status will be assessed using the ECOG scale, with Grades ranging from 0 to 5.
Measure:Serum levels of antidrug-antibodies (ADA) to GSK3359609 ICOS agonist.
Time Frame:Predose on Weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 37, 49, 61, 73, 85 and 97
Safety Issue:
Description:Serum samples will be collected and tested for the presence of antibodies that bind to GSK3359609 (ICOS agonist).
Measure:Maximum observed concentration (Cmax) for GSK3359609 (ICOS agonist)
Time Frame:Predose on Weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 37, 49, 61, 73, 85 and 97; end of infusion (within 5 minutes) and 4 hours post end of infusion on Week 1; end of infusion (within 5 minutes) at Weeks 13 and 25.
Safety Issue:
Description:Blood samples will be collected at indicated time points to calculate Cmax for GSK3359609 (ICOS agonist).
Measure:Cmax for SoC (docetaxel)
Time Frame:Predose on Day 1; end of SoC infusions (within 5 minutes) at Weeks 1, 4, 7, 10, 13, 16, 19 and 22; Between 2 and 5 hours after SoC infusion at Weeks 1, 4, 7, 10, 13, 16, 19 and 22
Safety Issue:
Description:Blood samples will be collected at indicated time points to calculate Cmax for Soc (docetaxel).
Measure:Minimum observed concentration (Cmin) for GSK3359609 (ICOS agonist)
Time Frame:Predose on Weeks 1, 4, 7, 10, 13, 16, 19, 22, 25, 37, 49, 61, 73, 85 and 97; end of infusion (within 5 minutes) and 4 hours post end of infusion on Week 1; end of infusion (within 5 minutes) at Weeks 13 and 25.
Safety Issue:
Description:Blood samples will be collected at indicated time points to calculate Cmin for GSK3359609 (ICOS agonist).
Measure:Cmin for SoC (docetaxel)
Time Frame:Predose on Day 1; end of SoC infusions (within 5 minutes) at Weeks 1, 4, 7, 10, 13, 16, 19 and 22; Between 2 and 5 hours after SoC infusion at Weeks 1, 4, 7, 10, 13, 16, 19 and 22
Safety Issue:
Description:Blood samples will be collected at indicated time points to calculate Cmin for Soc (docetaxel).

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:GlaxoSmithKline

Trial Keywords

  • Non-small cell lung cancer
  • Inducible t-cell co-stimulator (ICOS)
  • docetaxel
  • Standard of care
  • Immuno-oncology agents

Last Updated