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.
- 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.
- 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
- 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
- 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.