Clinical Trials /

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 regimens (in combination or as single agents) to standard of care in participants with relapsed/refractory advanced NSCLC. The study will be conducted in two parts; Part 1 is an optional, non-randomized part based on safety and pharmacokinetics/pharmacodynamics (PK/PD) evaluation intended to generate additional data to qualify novel regimens for the randomized study. Part 2 is a randomized, Phase II study comparing the efficacy and safety of these novel regimens with SoC.

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

Recruiting

Phase:

Phase 1/Phase 2

Trial Eligibility

Document

Title

  • Brief Title: 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
DocetaxelPart 2: Participants receiving Docetaxel
GSK3359609 (feladilimab)Part 1: Participants receiving GSK3359609 (feladilimab) and Ipilimumab high dose
IpilimumabPart 1: Participants receiving GSK3359609 (feladilimab) and Ipilimumab high dose
NiraparibPart 1: Participants receiving GSK3359609 and Niraparib
DostarlimabPart 1: Participants receiving GSK3359609 and Dostarlimab plus Cobolimab
CobolimabPart 1: Participants receiving GSK3359609 and Dostarlimab plus Cobolimab

Purpose

This study will compare the clinical activity of novel regimens (in combination or as single agents) to standard of care in participants with relapsed/refractory advanced NSCLC. The study will be conducted in two parts; Part 1 is an optional, non-randomized part based on safety and pharmacokinetics/pharmacodynamics (PK/PD) evaluation intended to generate additional data to qualify novel regimens for the randomized study. Part 2 is a randomized, Phase II study comparing the efficacy and safety of these novel regimens with SoC.

Trial Arms

NameTypeDescriptionInterventions
Part 1: Participants receiving GSK3359609 (feladilimab) and Ipilimumab high doseExperimental
  • GSK3359609 (feladilimab)
  • Ipilimumab
Part 1: Participants receiving GSK3359609 and Ipilimumab low doseExperimental
  • GSK3359609 (feladilimab)
  • Ipilimumab
Part 1: Participants receiving GSK3359609 and NiraparibExperimental
  • GSK3359609 (feladilimab)
  • Niraparib
Part 1: Participants receiving GSK3359609 and Dostarlimab plus CobolimabExperimental
  • GSK3359609 (feladilimab)
  • Dostarlimab
  • Cobolimab
Part 2: Participants receiving DocetaxelActive Comparator
  • Docetaxel
Part 2: Participants receiving GSK3359609 and Docetaxel combinationExperimental
  • Docetaxel
  • GSK3359609 (feladilimab)
Part 2: Participants receiving GSK3359609 and Ipilimumab combinationExperimental
  • GSK3359609 (feladilimab)
  • Ipilimumab
Part 2: Participants receiving GSK3359609 and Niraparib combinationExperimental
  • GSK3359609 (feladilimab)
  • Niraparib
Part 2: Participants receiving GSK3359609 and Dostarlimab plus Cobolimab combinationExperimental
  • GSK3359609 (feladilimab)
  • Dostarlimab
  • Cobolimab

Eligibility Criteria

        Inclusion Criteria:

          -  Participants capable of giving signed informed consent/assent.

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

          -  Participants with histologically or cytologically confirmed diagnosis of NSCLC
             (squamous or non-squamous) 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. No more than or less than 1 line of platinum-containing chemotherapy
             regimen, and ii. No more than or less than 1 line of Programmed cell death ligand 1
             (PD[L]1) monoclonal antibody (mAb) containing regimen. b. Participants 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.

        Exclusion Criteria:

          -  Participants 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 an 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 participants with BRAF
             molecular alternations.

          -  Invasive malignancy or history of invasive malignancy other than disease under study
             within the last 2 years, except a: Any other invasive malignancy for which the
             participant was definitively treated, has been disease-free for at least 2 years and
             in the opinion of the principal investigator and GSK Medical Monitor will not affect
             the evaluation of the effects of the study treatment on the currently targeted
             malignancy, may be included in this clinical trial. b: Curatively treated non-melanoma
             skin cancer or successfully treated in situ carcinoma.

          -  Central nervous system (CNS) metastases, with the following exception: Participants
             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.

          -  Receiving systemic steroids (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.

          -  Participants with known human immunodeficiency virus infection.

          -  Participants with history of severe hypersensitivity to mAb or hypersensitivity to
             ingredients used in the formulation of docetaxel.

          -  Participants requiring ongoing therapy with a medication that is a strong inhibitor or
             inducer of the cytochrome P 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 participants.

          -  Participant who 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.

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

          -  Participants with positive hepatitis C antibody test result at screening or within 3
             months prior to first dose of study intervention.

          -  Participants with positive hepatitis C ribonucleic acid (RNA) test result at screening
             or within 3 months prior to first dose of study treatment.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part 1: Number of participants with any adverse events (AEs) and serious adverse events (SAEs)
Time Frame:Up to 2 years
Safety Issue:
Description:AEs and SAEs will be collected.

Secondary Outcome Measures

Measure:Part 1: Objective response rate
Time Frame:Up to 2 years
Safety Issue:
Description:Objective response rate will be calculated as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. It is defined as the percentage of participants with a best overall confirmed complete response (CR) at any time as per disease-specific criteria.
Measure:Part 1: Disease control rate (DCR)
Time Frame:Up to 2 years
Safety Issue:
Description:DCR for GSK3359609 in combination with novel regimens will be evaluated.
Measure:Part 2: Survival rate at 12 and 18 months
Time Frame:12 and 18 months
Safety Issue:
Description:Milestone survival rate of participants treated with experimental regimens versus SoC therapy.
Measure:Part 2: Number of participants with CR, Partial response (PR), Stable disease (SD) and Progressive disease (PD)
Time Frame:Up to 3 years
Safety Issue:
Description:CR, PR, SD and PD will be evaluated as per RECIST version 1.1 criteria.
Measure:Part 2: Progression-free survival (PFS)
Time Frame:Up to 3 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:Part 2: Overall response rate (ORR)
Time Frame:Up to 3 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:Part 2: Duration of response (DOR)
Time Frame:Up to 3 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:Part 2: Number of participants with immune-based (i) iCR, iPR, unconfirmed progressive disease (iUPD), confirmed progressive disease (iCPD), and iSD
Time Frame:Up to 3 years
Safety Issue:
Description:Number of participants with iCR, iPR, iUPD, iCPD and iSD per modified RECIST 1.1 for immune-based therapeutics (iRECIST) criteria.
Measure:Part 2: Progression-free survival (iPFS)
Time Frame:Up to 3 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:Part 2: Overall response rate (iORR)
Time Frame:Up to 3 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:Part 2: Duration of response (iDOR)
Time Frame:Up to 3 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:Part 2: Number of participants with AEs, adverse events of special interest (AESI), SAEs and AE/SAEs leading to dose modifications/delays/withdrawals
Time Frame:Up to 2 years
Safety Issue:
Description:AEs, AESIs, SAEs and AE/SAEs leading to dose modifications/delays/withdrawals will be collected.
Measure:Part 1: Number of participants with clinically significant changes in vital signs, physical examination, ECG and laboratory parameters
Time Frame:Up to 2 years
Safety Issue:
Description:Number of participants with clinically significant changes in vital signs, physical examination, ECG and laboratory parameters will be assessed.
Measure:Part 2: Change from Baseline in ECOG PS score
Time Frame:Up to 2 years
Safety Issue:
Description:Performance status will be assessed using the ECOG scale, with Grades ranging from 0 to 5.
Measure:Part 2: Serum levels of antidrug-antibodies (ADA) to GSK3359609 ICOS agonist.
Time Frame:Up to 2 years
Safety Issue:
Description:Serum samples will be collected and tested for the presence of antibodies that bind to GSK3359609 (ICOS agonist).
Measure:Part 2: Maximum observed concentration (Cmax) and Minimum observed concentration (Cmin) for GSK3359609 (ICOS agonist)
Time Frame:Up to 2.3 years
Safety Issue:
Description:Blood samples will be collected for the concentrations of GSK3359609 (ICOS agonist)
Measure:Part 2: Cmax and Cmin for SoC (docetaxel)
Time Frame:Up to 2 years
Safety Issue:
Description:Blood samples will be collected for the concentrations of docetaxel
Measure:Part 2: Cmax and Cmin for Ipilimumab
Time Frame:Up to 2.3 years
Safety Issue:
Description:Blood samples will be collected for the concentrations of Ipilimumab.
Measure:Part 2: Cmax and Cmin for Niraparib
Time Frame:Up to 2 years
Safety Issue:
Description:Blood samples will be collected for the concentrations of niraparib.
Measure:Part 2: Cmax and Cmin for Dostarlimab
Time Frame:Up to 2.3 years
Safety Issue:
Description:Blood samples will be collected for the concentrations of dostarlimab.
Measure:Part 2: Cmax and Cmin for Cobolimab
Time Frame:Up to 2.5 years
Safety Issue:
Description:Blood samples will be collected for the concentrations of cobolimab.
Measure:Part 2: Number of participants with ADA for GSK3359609 (ICOS agonist).
Time Frame:Up to 2.5 years
Safety Issue:
Description:Serum samples will be collected and tested for the presence of antibodies that bind to GSK3359609 (ICOS agonist).
Measure:Part 2: Number of participants with ADA for Ipilimumab
Time Frame:Up to 2.5 years
Safety Issue:
Description:Serum samples will be collected and tested for the presence of antibodies that bind to ipilimumab
Measure:Part 2: Number of participants with ADA for dostarlimab
Time Frame:2.3 years
Safety Issue:
Description:Serum samples will be collected and tested for the presence of antibodies that bind to dostarlimab
Measure:Part 2: Number of participants with ADA for cobolimab
Time Frame:2.5 years
Safety Issue:
Description:Serum samples will be collected and tested for the presence of antibodies that bind to cobolimab

Details

Phase:Phase 1/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

June 1, 2021