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

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ClinicalTrials.gov Identifier: NCT03739710
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : July 15, 2021
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Docetaxel Drug: GSK3359609 (feladilimab) Drug: Ipilimumab Drug: Niraparib Drug: Dostarlimab Drug: Cobolimab Phase 1 Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 341 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Masking Description: The study will be open-label.
Primary Purpose: Treatment
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
Actual Study Start Date : January 24, 2019
Estimated Primary Completion Date : March 5, 2025
Estimated Study Completion Date : March 5, 2025

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Part 1: Participants receiving GSK3359609 (feladilimab) and Ipilimumab high dose Drug: GSK3359609 (feladilimab)
GSK3359609 will be administered as an IV infusion

Drug: Ipilimumab
Ipilimumab will be administered as an IV infusion

Experimental: Part 1: Participants receiving GSK3359609 and Ipilimumab low dose Drug: GSK3359609 (feladilimab)
GSK3359609 will be administered as an IV infusion

Drug: Ipilimumab
Ipilimumab will be administered as an IV infusion

Experimental: Part 1: Participants receiving GSK3359609 and Niraparib Drug: GSK3359609 (feladilimab)
GSK3359609 will be administered as an IV infusion

Drug: Niraparib
Niraparib will be administered orally

Experimental: Part 1: Participants receiving GSK3359609 and Dostarlimab plus Cobolimab Drug: GSK3359609 (feladilimab)
GSK3359609 will be administered as an IV infusion

Drug: Dostarlimab
Dostarlimab will be administered as an IV infusion

Drug: Cobolimab
Cobolimab will be administered as an IV infusion

Active Comparator: Part 2: Participants receiving Docetaxel Drug: Docetaxel
Docetaxel will be administered as an intravenous (IV) infusion.

Experimental: Part 2: Participants receiving GSK3359609 and Docetaxel combination Drug: Docetaxel
Docetaxel will be administered as an intravenous (IV) infusion.

Drug: GSK3359609 (feladilimab)
GSK3359609 will be administered as an IV infusion

Experimental: Part 2: Participants receiving GSK3359609 and Ipilimumab combination Drug: GSK3359609 (feladilimab)
GSK3359609 will be administered as an IV infusion

Drug: Ipilimumab
Ipilimumab will be administered as an IV infusion

Experimental: Part 2: Participants receiving GSK3359609 and Niraparib combination Drug: GSK3359609 (feladilimab)
GSK3359609 will be administered as an IV infusion

Drug: Niraparib
Niraparib will be administered orally

Experimental: Part 2: Participants receiving GSK3359609 and Dostarlimab plus Cobolimab combination Drug: GSK3359609 (feladilimab)
GSK3359609 will be administered as an IV infusion

Drug: Dostarlimab
Dostarlimab will be administered as an IV infusion

Drug: Cobolimab
Cobolimab will be administered as an IV infusion




Primary Outcome Measures :
  1. Part 1: Number of participants with any adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 2 years ]
    AEs and SAEs will be collected.

  2. Part 1: Number of participants with dose limiting toxicity (DLT) [ Time Frame: Up to 2 years ]
    DLTs will be assessed.

  3. Part 1: Number of participants with clinically significant changes in vital signs, physical examination, electrocardiogram (ECG) and laboratory parameters [ Time Frame: Up to 2 years ]
    Number of participants with clinically significant changes in vital signs, physical examination, ECG and laboratory parameters will be assessed.

  4. Part 1: Change from Baseline in Eastern Cooperative Oncology Group (ECOG) performance status (PS) score [ Time Frame: Up to 2 years ]
    Performance status will be assessed using the ECOG scale, with Grades ranging from 0 to 5.

  5. Part 1: Number of participants requiring dose modifications [ Time Frame: Up to 2 years ]
    All dose modifications due to any reasons will be recorded.

  6. Part 2: Overall survival rate [ Time Frame: Up to 3 years ]
    Overall survival rate will be calculated as time from randomization to death.


Secondary Outcome Measures :
  1. Part 1: Objective response rate [ Time Frame: Up to 2 years ]
    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.

  2. Part 1: Disease control rate (DCR) [ Time Frame: Up to 2 years ]
    DCR for GSK3359609 in combination with novel regimens will be evaluated.

  3. Part 2: Survival rate at 12 and 18 months [ Time Frame: 12 and 18 months ]
    Milestone survival rate of participants treated with experimental regimens versus SoC therapy.

  4. Part 2: Number of participants with CR, Partial response (PR), Stable disease (SD) and Progressive disease (PD) [ Time Frame: Up to 3 years ]
    CR, PR, SD and PD will be evaluated as per RECIST version 1.1 criteria.

  5. Part 2: Progression-free survival (PFS) [ Time Frame: Up to 3 years ]
    PFS is defined as time from the date of randomization to the date of disease progression or death whichever occurs earlier.

  6. Part 2: Overall response rate (ORR) [ Time Frame: Up to 3 years ]
    ORR is defined as the percentage of participants with a confirmed CR or PR at any time per RECIST version 1.1 criteria.

  7. Part 2: Duration of response (DOR) [ Time Frame: Up to 3 years ]
    DOR is defined as the first documented evidence of CR or PR until disease progression or death, per RECIST 1.1 criteria.

  8. 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 ]
    Number of participants with iCR, iPR, iUPD, iCPD and iSD per modified RECIST 1.1 for immune-based therapeutics (iRECIST) criteria.

  9. Part 2: Progression-free survival (iPFS) [ Time Frame: Up to 3 years ]
    PFS is defined as time from the date of randomization to the date of disease progression or death, whichever occurs earlier, per iRECIST criteria.

  10. Part 2: Overall response rate (iORR) [ Time Frame: Up to 3 years ]
    ORR is defined as the percentage of participants with a confirmed CR or PR at any time per iRECIST criteria.

  11. Part 2: Duration of response (iDOR) [ Time Frame: Up to 3 years ]
    iDOR is defined as the first documented evidence of CR or PR until disease progression or death, per iRECIST criteria.

  12. 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 ]
    AEs, AESIs, SAEs and AE/SAEs leading to dose modifications/delays/withdrawals will be collected.

  13. Part 1: Number of participants with clinically significant changes in vital signs, physical examination, ECG and laboratory parameters [ Time Frame: Up to 2 years ]
    Number of participants with clinically significant changes in vital signs, physical examination, ECG and laboratory parameters will be assessed.

  14. Part 2: Change from Baseline in ECOG PS score [ Time Frame: Up to 2 years ]
    Performance status will be assessed using the ECOG scale, with Grades ranging from 0 to 5.

  15. Part 2: Serum levels of antidrug-antibodies (ADA) to GSK3359609 ICOS agonist. [ Time Frame: Up to 2 years ]
    Serum samples will be collected and tested for the presence of antibodies that bind to GSK3359609 (ICOS agonist).

  16. Part 2: Maximum observed concentration (Cmax) and Minimum observed concentration (Cmin) for GSK3359609 (ICOS agonist) [ Time Frame: Up to 2.3 years ]
    Blood samples will be collected for the concentrations of GSK3359609 (ICOS agonist)

  17. Part 2: Cmax and Cmin for SoC (docetaxel) [ Time Frame: Up to 2 years ]
    Blood samples will be collected for the concentrations of docetaxel

  18. Part 2: Cmax and Cmin for Ipilimumab [ Time Frame: Up to 2.3 years ]
    Blood samples will be collected for the concentrations of Ipilimumab.

  19. Part 2: Cmax and Cmin for Niraparib [ Time Frame: Up to 2 years ]
    Blood samples will be collected for the concentrations of niraparib.

  20. Part 2: Cmax and Cmin for Dostarlimab [ Time Frame: Up to 2.3 years ]
    Blood samples will be collected for the concentrations of dostarlimab.

  21. Part 2: Cmax and Cmin for Cobolimab [ Time Frame: Up to 2.5 years ]
    Blood samples will be collected for the concentrations of cobolimab.

  22. Part 2: Number of participants with ADA for GSK3359609 (ICOS agonist). [ Time Frame: Up to 2.5 years ]
    Serum samples will be collected and tested for the presence of antibodies that bind to GSK3359609 (ICOS agonist).

  23. Part 2: Number of participants with ADA for Ipilimumab [ Time Frame: Up to 2.5 years ]
    Serum samples will be collected and tested for the presence of antibodies that bind to ipilimumab

  24. Part 2: Number of participants with ADA for dostarlimab [ Time Frame: 2.3 years ]
    Serum samples will be collected and tested for the presence of antibodies that bind to dostarlimab

  25. Part 2: Number of participants with ADA for cobolimab [ Time Frame: 2.5 years ]
    Serum samples will be collected and tested for the presence of antibodies that bind to cobolimab



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03739710


Contacts
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Contact: US GSK Clinical Trials Call Center 877-379-3718 GSKClinicalSupportHD@gsk.com
Contact: EU GSK Clinical Trials Call Center +44 (0) 20 89904466 GSKClinicalSupportHD@gsk.com

Locations
Show Show 68 study locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
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Study Director: GSK Clinical Trials GlaxoSmithKline
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Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT03739710    
Other Study ID Numbers: 205801
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: July 15, 2021
Last Verified: July 2021
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted when justified, for up to another 12 months.
URL: http://clinicalstudydatarequest.com

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by GlaxoSmithKline:
Non-small cell lung cancer
Inducible t-cell co-stimulator (ICOS)
docetaxel
Standard of care
Immuno-oncology agents
Additional relevant MeSH terms:
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Docetaxel
Ipilimumab
Niraparib
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors
Poly(ADP-ribose) Polymerase Inhibitors
Enzyme Inhibitors