MC# 18-20 - A Phase II, Randomized, Open-label Platform Trial Utilizing a Master Protocol to Study Novel Regimens Versus Standard of Care Treatment in NSCLC Participants

  • Agent(s): GSK3359609
  • Disease Type(s): Lung-NSCLC
  • Phase(s): II
  • Drug Classification(s): Targeted Therapy, Immunotherapy, Monoclonal Antibody
  • Molecular Target(s): ICOS

Mechanism of Action

GSK3359609, an anti-ICOS agonist antibody, targets and binds to ICOS expressed on tumor infiltrating CD4-positive T cells. This stimulates ICOS-positive T-cell proliferation, enhances cytotoxic T-lymphocyte (CTL) survival and increases CTL-mediated immune responses against tumor cells.

Purpose

In this study, the sponsor and investigators want to learn:

  • The effects of GSK3359609 when given in combination with Docetaxel compared to being given only Docetaxel
  • how fast GSK3359609 is removed from the body
  • If research tests can be used in the future to predict who will benefit from GSK3359609
Inclusion Criteria
  • Capable of giving signed informed consent/assent, which includes compliance with the requirements and restrictions listed in the ICF and in the protocol
  • Male or female, aged 18 years or older at the time consent is obtained
  • Histologically or cytologically confirmed diagnosis of NSCLC (squamous or non- squamous) and
    • 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.
      • A maximum of 1 line of platinum-containing chemotherapy regimen in the metastatic setting, and
      • A maximum of 1 line of PD(L)1 mAb containing regimen.
        • PD(L)1 mAb received during a previous clinical trial may meet this requirement upon consultation with study medical monitor.
        • Participants on the phase III PACIFIC trial (NCT02125461) experimental regimen (chemoradiotherapy followed by durvalumab) or received the PACIFIC regimen [chemoradiotherapy followed by PD(L)1] as part of SoC AND have relapsed within one year from the first dose of chemoradiotherapy would fulfill the protocol requirement for platinum-based chemotherapy treatment and PD-1 treatment. This would be considered a single line of treatment for the purpose of PD(L)1 line of therapy stratification.
        • PD(L)1 mAb can be administered with the platinum-based chemotherapy regimen and this would count as a single line of therapy.
        • PD(L)1 mAb may be counted as a prior treatment if the agent is approved in at least 1 country for the treatment of cancer.
        • Participants who have completed 2 years of pembrolizumab or another PD(L)1 mAb, 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.
        • Adjuvant or neo-adjuvant systemic anticancer therapy will not count toward the 2 lines of therapy unless disease recurs during the first year following the start of adjuvant chemotherapy.
    • 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
  • Eastern Cooperative Oncology Group (ECOG) Performance Status (PS) score of 0 or
  • 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 as defined in Table 6.

    Table 6                

     

    System

    Laboratory Values

    Hematologica

    ANC (Absolute Neutrophil Count)

    ≥1.5 x 109/L (≥1500/µL)

    ALC (Absolute Lymphocyte Count)

    ≥800/mm3

    Hemoglobin

    ≥9 g/dL or ≥5.6 mmol/L

    Platelets

    ≥100 x 109/L (≥100 000/µL)

    Hepatic

    Albumin

    ≥2.5 g/dL

    Total bilirubin

    Patients with Gilbert’s Syndrome (only if direct bilirubin <35%)

    ≤1.5 x ULN (isolated bilirubin ≤1.5 x ULN is acceptable if bilirubin is fractionated and direct bilirubin <35%)

    ALT (SGPT)

    ≤2.5 x ULN, OR

    ≤5 X ULN for participants with documented liver metastases

    Renal

    Calculated CrClb

    ≥30 mL/min

  • A male participant 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. Note: If the participant is randomized to the SoC regimen only, then the duration of contraception is at least 3 days after the last dose of study treatment.
  • A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions apply:
    • 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. Note: If the participant is randomized to the SoC regimen only, then the duration of contraception is at least 3 days after the last dose of study treatment (or per institutional standard)
Exclusion Criteria
  • Received prior treatment with the following therapies (calculation is based on date of last therapy to date of first dose of study treatment):
    • Docetaxel at any time
    • Any of the investigational agents being tested in the current study, including experimental ICOS agonist
    • 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.
    • 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 participants with BRAF molecular alternations. (See inclusion criterion #3 for eligible lines of therapy guidance) Note: Patients with known EGFR/ALK/ROS1 molecular alterations are excluded from participation in this study.
  • Invasive malignancy or history of invasive malignancy other than disease under study within the last 2 years, except as noted below:
    • Any other invasive malignancy for which the participant was definitively treated, has been disease-free for ≤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.
    • 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. Note: Participants with carcinomatous meningitis or leptomeningeal spread are excluded regardless of clinical stability.
  • 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 mg oral prednisone or equivalent) or other immunosuppressive agents within 7 days prior to first dose of study treatment. Note: Steroids as premedication for hypersensitivity reactions (e.g., computed tomography [CT] scan premedication) are permitted.
  • Prior allogeneic/autologous bone marrow or solid organ transplantation.
  • Receipt of any live vaccine within 30 days prior to first dose of study treatment. Examples of live vaccines include, but are not limited to the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (for example, FluMist) are live attenuated vaccines and are not allowed.
  • Toxicity from previous anticancer treatment that includes:
    • ≥ Grade 3 toxicity considered related to prior immunotherapy and that led to treatment discontinuation.
    • 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. Note: post-radiation changes in the lung related to prior radiotherapy and/or asymptomatic radiation-induced pneumonitis not requiring treatment may be permitted if agreed upon by the investigator and Medical Monitor.
  • 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 which include:
    • Serious, uncontrolled cardiac arrhythmia or clinically significant electrocardiogram abnormalities including second degree (Type II) or third degree atrioventricular block.
    • Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting or bypass grafting
    • Symptomatic pericarditis.
  • Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis. Note: Stable chronic liver disease (including Gilbert's syndrome or asymptomatic gallstones) is acceptable if participant otherwise meets entry criteria.
  • Active infection requiring systemic therapy.
  • Known human immunodeficiency virus infection, or positive test for hepatitis B active infection (presence of hepatitis B surface antigen), or hepatitis C active infection.
  • History of severe hypersensitivity to monoclonal antibodies or hypersensitivity to ingredients used in the formulation of docetaxel.
  • Requires ongoing therapy with a medication that is a strong inhibitor or inducer of the cytochrome 3A4 (CYP3A4) enzymes.  This criterion is applicable to only those participants in treatment arms containing docetaxel.
  • 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
  • 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.

Location

  • Dallas, TX - Mary Crowley Cancer Research - Medical City
More Info: https://clinicaltrials.gov/ct2/show/NCT03739710?term=GSK3359609&phase=1&rank=2

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Re: MC# 18-20