A Phase II, Randomized, Open-label Platform Trial Utilizing a MastercProtocol to Study Novel Regimens Versus Standard of Care Treatment in NSCLC Participants (study 205801)

Non-small cell lung cancer (NSCLC) in general is considered to be intrinsically
resistant to immuno-oncology agents However, as shown by the single-agent
response rates of anti-PD-1 inhibitors in NSCLC, a subset of tumors are
susceptible to T cell-mediated antitumor effects, suggesting those tumors have
some degree of prior T-cell immunity. Since effective anticancer immune
response involves stepwise processes, lung cancers may possess or acquire
features that enable them to evade immune surveillance, suppress immune
reactivity, proliferate, and survive within an inflammatory microenvironment
thereby rendering an immune response ineffectual. Therefore, treatment
modalities that incorporate combinations with agents targeting different
processes within the immune cascade have the potential to reinstate
immuno-surveillance; these may include regimens containing chemotherapy that
possess advantageous immunological effects to improve clinical efficacy.
Study 205801 is a Phase II platform trial designed to investigate the clinical
activity of novel regimens consisting of immuno-oncology agents compared with
standard of care (SoC) regimen in participants with relapsed/refractory
advanced non-small cell lung cancer (NSCLC) who have failed a prior
platinum-containing regimen and an immuno-oncology agent, such as
anti-programmed cell death protein 1 [PD-1] / PD-Ligand 1 [PD-L1] - either in
combination or as separate lines.
The study will initially evaluate 2 treatment regimens/arms, but additional
regimens/arms may be added via future protocol amendment(s) (see the Study
Design on protocol page 13). Each additional treatment arm/regimen will be
analyzed relative to the SoC treatment and is considered a sub-study within the
overall master protocol.
The study will initially evaluate the efficacy of GSK3359609 (ICOS Agonist) in
combination with SoC (docetaxel) compared with SoC alone as the standard
subsequent line chemotherapy (sub-study 1) in NSCLC.

Protocolamendment 03:
Addition of three new substudies.
• Sub study 2 - GSK3369609 with Ipilimumab
• Sub study 3 - GSK3369609 with Niraparib
• Sub study 4 - GSK3369609 with Dostarlimab and Cobolimab
The Netherlands will not participate in these substudies.

Protocolamendment 04 contains clarifications of the sub-studies. These are
the most important changes that apply to the Netherlands:
• GSK3359609 has been named feladilimab
• Addition of a primary analysis by 75 death events

Primary:
To determine whether experimental regimens provide evidence for improved
survival (randomization to death) over standard of care (SoC) therapy in NSCLC
patients.
Secondary:
Milestone survival, measures of antitumor activity, safety and tolerability, PK
parameters of GSK3359609 (ICOS Agonist) given in combination with chemotherapy
and/or other immunotherapies.

Open-label, randomized, multicenter phase II platform trial utilizing a master
protocol designed to study novel immunotherapy drug combinations compared with
the current SoC, in the treatment of patients with advanced NSCLC.
The study will initially evaluate 2 treatment regimens/arms (sub-study 1), but
additional regimens/arms may be added via future protocol amendment(s) (see the
Study Design on protocol page 13).
Participants will be stratified by histology (squamous vs. non-squamous) and
line of PD(L)1 therapy (1st vs. 2nd line).
Each additional treatment arm/regimen will be analyzed relative to the SoC
treatment and is considered a sub-study within the overall master protocol, as
depicted on protocol page 13.
Maximum number of subjects for sub-study 2 and above: 70.

Sub-study 1:
Comparison of IV administered docetaxel ± GSK3359609. Randomization
D:D+GSK-1:2. Study duration: 2 years or 35 treatment visits, whichever comes
first, or until disease progression or unacceptable toxicity. Docetaxel may be
continued until disease progression or unacceptable toxicity. Follow-up for
survival (every 12 weeks by phone). 105 subjects.

Treatment with docetaxel monotherapy or docetaxel in combination with
GSK3359609.

Risk: Adverse events of the study medication. First in human study.
Burden:
• Max. approx. 40 visits. Thereafter survival follow-up (phone call every 12
weeks).
Based on 2 study years:
• Max. 35 infusions GSK3359609, 30 min. per infusion of 250 ml and max. approx.
35 infusions docetaxel 1 hour per infusion of 500 ml.
• Physical examination: 20 times.
• Blood draws: 37 times. 25-60 mL blood per occasion.
• ECG en echocardiography (alternative: MUGA scan): once.
• CT/MRI scan every 6-12 weeks.
• Questionnaires: 3-7 per occasion (PRO-CTCAE, FACT-G item 5, NSCLC-SAQ,
QLQ-LC13, PROMIS-PF, QLQ-C30, PGRS/PGIC).
• Tumor biopsy: 0-1.
Optional:
• Blood sample for pharmacogenetics (6 mL).
• Tumor biopsy: 5 times.