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.
- 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.
- 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
- 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
- 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
- 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.