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Phase II 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 : June 12, 2019
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Neoplasms Drug: Docetaxel Drug: GSK3359609 (ICOS Agonist) Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 105 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 : June 16, 2020
Estimated Study Completion Date : March 29, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Docetaxel

Arm Intervention/treatment
Experimental: Subjects receiving GSK3359609 (ICOS Agonist) + Docetaxel
Subjects 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.
Drug: Docetaxel
Docetaxel will be administered as an intravenous (IV) infusion at a dose of 75 milligram per meter squared (mg/m^2) once every three weeks.

Drug: GSK3359609 (ICOS Agonist)
GSK3359609 will be administered as an IV infusion at a dose of 80 mg once every 3 weeks.

Active Comparator: Subjects receiving Docetaxel
Subjects will receive docetaxel once in every 3 weeks as an intravenous infusion.
Drug: Docetaxel
Docetaxel will be administered as an intravenous (IV) infusion at a dose of 75 milligram per meter squared (mg/m^2) once every three weeks.




Primary Outcome Measures :
  1. Time of overall survival [ Time Frame: Up to 106 Weeks ]
    Overall survival time of subjects from randomization to death will be evaluated.


Secondary Outcome Measures :
  1. Survival rate at 12 months [ Time Frame: Up to 12 months ]
    Milestone survival rate of participants treated with experimental regimens versus SoC therapy.

  2. Survival rate at 18 months [ Time Frame: Up to 18 months ]
    Milestone survival rate of participants treated with experimental regimens versus SoC therapy.

  3. Number of participants with Complete response (CR) [ Time Frame: Up to 4 years ]
    Number of participants with CR as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria.

  4. Number of participants with Partial response (PR) [ Time Frame: Up to 4 years ]
    Number of participants with PR as per RECIST version 1.1 criteria.

  5. Number of participants with Stable disease (SD) [ Time Frame: Up to 4 years ]
    Number of participants with SD as per RECIST version 1.1 criteria.

  6. Number of participants with Progressive disease (PD) [ Time Frame: Up to 4 years ]
    Number of participants with PD as per RECIST version 1.1 criteria.

  7. Progression-free survival (PFS) [ Time Frame: Up to 4 years ]
    PFS is defined as time from the date of randomization to the date of disease progression or death whichever occurs earlier.

  8. Overall response rate (ORR) [ Time Frame: Up to 4 years ]
    ORR is defined as the percentage of participants with a confirmed CR or PR at any time per RECIST version 1.1 criteria.

  9. Duration of response (DOR) [ Time Frame: Up to 4 years ]
    DOR is defined as the first documented evidence of CR or PR until disease progression or death, per RECIST 1.1 criteria.

  10. Number of participants with iCR [ Time Frame: Up to 4 years ]
    Number of participants with iCR per modified RECIST 1.1 for immune-based therapeutics (iRECIST) criteria.

  11. Number of participants with iPR [ Time Frame: Up to 4 years ]
    Number of participants with iPR per iRECIST criteria.

  12. Number of participants with unconfirmed progressive disease (iUPD) [ Time Frame: Up to 4 years ]
    Number of participants with iUPD per iRECIST criteria.

  13. Number of participants with confirmed progressive disease (iCPD) [ Time Frame: Up to 4 years ]
    Number of participants with iCPD per iRECIST criteria.

  14. Number of participants with iSD [ Time Frame: Up to 4 years ]
    Number of participants with iSD per iRECIST criteria.

  15. Progression-free survival (iPFS) [ Time Frame: Up to 4 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.

  16. Overall response rate (iORR) [ Time Frame: Up to 4 years ]
    ORR is defined as the percentage of participants with a confirmed CR or PR at any time per iRECIST criteria.

  17. Duration of response (iDOR) [ Time Frame: Up to 4 years ]
    iDOR is defined as the first documented evidence of CR or PR until disease progression or death, per iRECIST criteria.

  18. Number of participants with adverse events (AE) [ Time Frame: Up to 2 years ]
    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.

  19. Number of participants with Adverse events of special interest (AESI) [ Time Frame: Up to 2 years ]
    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).

  20. Number of participants with Serious adverse events (SAE) [ Time Frame: Up to 2 years ]
    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.

  21. Number of participants with AEs or SAEs leading to dose modification [ Time Frame: Up to 2 years ]
    Participants who underwent dose modification due to AEs or SAEs will be recorded.

  22. Number of participants with AEs or SAEs leading to dose delays [ Time Frame: Up to 2 years ]
    Participants will have dose delays due to AEs or SAEs will be recorded.

  23. Number of participants with AEs or SAEs leading to withdrawals [ Time Frame: Up to 2 years ]
    Participants who withdrew from the study due to AEs or SAEs will be recorded.

  24. Change from Baseline in temperature [ Time Frame: Baseline and up to 106 Weeks ]
    Temperature will be measured after 5 minutes of rest.

  25. Change from Baseline in systolic blood pressure (SBP) and diastolic blood pressure (DBP) [ Time Frame: Baseline and up to 106 Weeks ]
    Blood pressure both systolic and diastolic will be measured after 5 minutes of rest.

  26. Change from Baseline in pulse rate [ Time Frame: Baseline and up to 106 Weeks ]
    Pulse rate will be measured after 5 minutes of rest.

  27. Change from Baseline in respiratory rate [ Time Frame: Baseline and up to 106 Weeks ]
    Respiratory rate will be measured after 5 minutes of rest.

  28. Change from Baseline in oxygen saturation [ Time Frame: Baseline and up to 106 Weeks ]
    Oxygen saturation will be measured after 5 minutes of rest.

  29. Change from Baseline of hematology parameters: eosinophils, lymphocytes, monocytes, basophils, neutrophils, platelet and leukocytes [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameters such as eosinophils, lymphocytes, monocytes, basophils, neutrophils, platelet and leukocytes will be evaluated.

  30. Change from Baseline of hematology parameters: hematocrit [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameter such as hematocrit will be evaluated.

  31. Change from Baseline of hematology parameter: hemoglobin [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameter such as hemoglobin will be evaluated.

  32. Change from Baseline of hematology parameter: mean corpuscular hemoglobin [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameter such as mean corpuscular hemoglobin will be evaluated.

  33. Change from Baseline of hematology parameter: mean corpuscular volume [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameter such as mean corpuscular volume will be evaluated.

  34. Change from Baseline in hematology parameter: Red blood cell (RBC) count [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameter such as RBC count will be evaluated.

  35. Change from Baseline of Clinical chemistry parameters: glucose, sodium, Blood Urea Nitrogen (BUN), calcium, and potassium [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameters such as glucose, sodium, BUN, calcium, and potassium will be evaluated.

  36. Change from Baseline of Clinical chemistry parameters: Alkaline Phosphatase, Alanine Aminotransferase (ALT), and Aspartate Aminotransferase (AST) [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameters such as alkaline phosphatase, ALT, and AST will be evaluated.

  37. Change from Baseline of Clinical chemistry parameters: Direct bilirubin, Bilirubin, Creatinine. [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameters such as direct bilirubin, bilirubin, and creatinine will be evaluated.

  38. Change from Baseline of Clinical chemistry parameters: lactate dehydrogenase (LDH) [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameter such as LDH will be evaluated.

  39. Change from Baseline of Clinical chemistry parameters: Total protein and albumin [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameters such as total protein and albumin will be evaluated.

  40. Change from Baseline in urinalysis parameters: ketones [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameter such as ketones will be evaluated.

  41. Change from Baseline in Urinalysis parameter: Specific gravity [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameter such as specific gravity will be evaluated.

  42. Change from Baseline in Urinalysis parameter: pH [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameter such as pH will be evaluated.

  43. Change from Baseline in Urinalysis parameter: glucose [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameter such as glucose will be evaluated.

  44. Change from Baseline in Urinalysis parameter: protein [ Time Frame: Baseline and up to 106 Weeks ]
    Change from Baseline for parameter such as protein will be evaluated.

  45. Change from Baseline in Eastern Cooperative Oncology Group (ECOG) performance status (PS) score [ Time Frame: Baseline and up to 106 Weeks ]
    Performance status will be assessed using the ECOG scale, with Grades ranging from 0 to 5.

  46. 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 ]
    Serum samples will be collected and tested for the presence of antibodies that bind to GSK3359609 (ICOS agonist).

  47. 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. ]
    Blood samples will be collected at indicated time points to calculate Cmax for GSK3359609 (ICOS agonist).

  48. 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 ]
    Blood samples will be collected at indicated time points to calculate Cmax for Soc (docetaxel).

  49. 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. ]
    Blood samples will be collected at indicated time points to calculate Cmin for GSK3359609 (ICOS agonist).

  50. 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 ]
    Blood samples will be collected at indicated time points to calculate Cmin for Soc (docetaxel).



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:

  • Subjects capable of giving signed informed consent/assent.
  • Male or female, aged 18 years or older at the time consent is obtained.
  • Subjects with histologically or cytologically confirmed diagnosis of NSCLC (squamous or non-squamous) and: a. Documented disease progression (for example, 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: 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 monoclonal antibody (mAb) containing regimen. iii. Participants who have completed 2 years of pembrolizumab or another PD (L)1mAb, discontinue from that therapy, experience disease progression, and are then retreated with PD (L)1, will be considered as having had one line of PD (L)1 therapy. 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.
  • 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 >=3 prior lines of therapy for NSCLC, including subjects with BRAF molecular alternations.
  • 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.
  • 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, or positive test for hepatitis B active infection (presence of hepatitis B surface antigen), or hepatitis C active 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 agent or has used an investigational device within 4 weeks prior to the 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

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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     History of Changes
Other Study ID Numbers: 205801
First Posted: November 14, 2018    Key Record Dates
Last Update Posted: June 12, 2019
Last Verified: May 2019
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 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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Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Docetaxel
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action