Platform Trial of Novel Regimens Versus Standard of Care (SoC) in Participants With Non-small Cell Lung Cancer (NSCLC)

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

This study will compare the clinical activity of novel regimens (in combination or as single agents) to SoC in participants with relapsed/refractory advanced NSCLC. The study will be conducted in two parts. Part 1 is an open-label, 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 open-label part comparing the efficacy and safety of these novel regimens with SoC. Drug name mentioned as GSK4428859A (belrestotug) and EOS884448 are interchangeable for the same compound and will be referred to as GSK4428859A/EOS884448/belrestotug.

Study Overview

• Status: Completed
• Conditions: Neoplasms
• Intervention / Treatment: Drug: Dostarlimab; Drug: Docetaxel; Drug: Feladilimab; Drug: Ipilimumab; Drug: GSK6097608; Drug: GSK4428859A

• Study Type: Interventional
• Enrollment (Actual): 175
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 1Z2
      • GSK Investigational Site
  • Ontario
    • Brampton, Ontario, Canada, L6R 3J7
      • GSK Investigational Site
    • Toronto, Ontario, Canada, M5G 2M9
      • GSK Investigational Site
• France
  • Bordeaux, France, 33076
    • GSK Investigational Site
  • Caen Cedex 9, France, 14033
    • GSK Investigational Site
  • Paris, France, 75018
    • GSK Investigational Site
  • Paris, France, 75248
    • GSK Investigational Site
  • Saint-Herblain, France, 44093
    • GSK Investigational Site
  • Villejuif Cedex, France, 94805
    • GSK Investigational Site
• Germany
  • Berlin, Germany, 14165
    • GSK Investigational Site
  • Gauting, Germany, 82131
    • GSK Investigational Site
  • Grosshansdorf, Germany, 22927
    • GSK Investigational Site
  • Heidelberg, Germany, 69126
    • GSK Investigational Site
  • Immenhausen, Germany, 34376
    • GSK Investigational Site
  • Kassel, Germany, 34125
    • GSK Investigational Site
  • Leipzig, Germany, 04357
    • GSK Investigational Site
• Italy
  • Meldola FC, Italy, 47014
    • GSK Investigational Site
  • Milano, Italy, 20133
    • GSK Investigational Site
  • Napoli, Italy, 80131
    • GSK Investigational Site
  • Orbassano TO, Italy, 10043
    • GSK Investigational Site
  • Ravenna, Italy, 48121
    • GSK Investigational Site
  • Siena, Italy, 53100
    • GSK Investigational Site
• Korea, Republic of
  • Cheongju Chungcheongbuk-do, Korea, Republic of, 28644
    • GSK Investigational Site
  • Gyeonggi-do, Korea, Republic of, 10408
    • GSK Investigational Site
  • Seongnam-si Gyeonggi-do, Korea, Republic of, 13620
    • GSK Investigational Site
  • Seoul, Korea, Republic of, 05505
    • GSK Investigational Site
• Netherlands
  • Amsterdam, Netherlands, 1081 HV
    • GSK Investigational Site
  • Maastricht, Netherlands, 6229 HX
    • GSK Investigational Site
• Poland
  • Lodz, Poland, 93-513
    • GSK Investigational Site
  • Poznan, Poland, 60-569
    • GSK Investigational Site
  • Warszawa, Poland, 02-781
    • GSK Investigational Site
• Romania
  • Bucharest, Romania, 020142
    • GSK Investigational Site
  • Craiova, Romania, 200347
    • GSK Investigational Site
  • Floresti, Romania, 407280
    • GSK Investigational Site
  • Otopeni, Romania, 075100
    • GSK Investigational Site
  • Timisoara, Romania, 300166
    • GSK Investigational Site
• Russian Federation
  • Chelyabinsk, Russian Federation, 454048
    • GSK Investigational Site
  • Saint-Petersburg, Russian Federation, 197183
    • GSK Investigational Site
  • St-Petersburg, Russian Federation, 194291
    • GSK Investigational Site
• Spain
  • Badajoz, Spain, 06080
    • GSK Investigational Site
  • Barcelona, Spain, 08036
    • GSK Investigational Site
  • Barcelona, Spain, 08035
    • GSK Investigational Site
  • Madrid, Spain, 28034
    • GSK Investigational Site
  • Madrid, Spain, 28027
    • GSK Investigational Site
  • Madrid, Spain, 28033
    • GSK Investigational Site
  • Malaga, Spain, 29010
    • GSK Investigational Site
  • Santander, Spain, 39008
    • GSK Investigational Site
  • Sevilla, Spain, 41009
    • GSK Investigational Site
• Sweden
  • Stockholm, Sweden, SE-171 64
    • GSK Investigational Site
  • Uppsala, Sweden, SE- 75 185
    • GSK Investigational Site
• United States
  • California
    • Los Angeles, California, United States, 90025
      • GSK Investigational Site
  • Missouri
    • Saint Louis, Missouri, United States, 63110-1093
      • GSK Investigational Site
  • New York
    • Bronx, New York, United States, 10461-2375
      • GSK Investigational Site
  • North Carolina
    • Pinehurst, North Carolina, United States, 28374
      • GSK Investigational Site
  • Tennessee
    • Chattanooga, Tennessee, United States, 37404
      • GSK Investigational Site
    • Nashville, Tennessee, United States, 37203
      • GSK Investigational Site
  • Texas
    • Dallas, Texas, United States, 75230
      • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 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 IIIc/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.

  c) Participants who received prior anti-PD(L)1 therapy must fulfill the following requirements: i) Have achieved a CR, PR or SD and subsequently had disease progression (per RECIST 1.1 criteria) either on or after completing PD(L)1 therapy ii) Have not progressed or recurred within the first 12 weeks of PD(L)1 therapy, either clinically or per RECIST 1.1 criteria

• 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 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 as defined in the protocol.
• 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.

• A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions apply:

  i) Not a woman of childbearing potential (WOCBP) or ii) 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.

• Life expectancy of at least 12 weeks.

Exclusion Criteria:

• 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):

  1. Docetaxel at any time.
  2. Any of the investigational agents being tested in the current study.
  3. 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.
  4. 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 greater than (>)2 prior lines of therapy for NSCLC, including participants with BRAF molecular alternations.

• Invasive malignancy or history of invasive malignancy other than disease under study within the last 2 years, except

  • 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 GlaxoSmithKline 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.
• Carcinomatous meningitis (regardless of clinical status) and uncontrolled or symptomatic Central nervous system (CNS) metastases.
• Major surgery less than or equal to (<=) 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 milligrams [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:

  1. Greater than or equal to (>=) Grade 3 toxicity considered related to prior immunotherapy and that led to treatment discontinuation.
  2. History of myocarditis of any grade during a previous treatment with immunotherapy
  3. 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 which include

  1. Serious, uncontrolled cardiac arrhythmia or clinically significant electrocardiogram abnormalities including second degree (Type II) or third degree atrioventricular block.
  2. Cardiomyopathy, myocardial infarction, acute coronary syndromes (including unstable angina pectoris), coronary angioplasty, stenting or bypass grafting.
  3. Symptomatic pericarditis.
• 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 <=7 days prior to first dose of study treatment.
• Participants with known human immunodeficiency virus infection.
• Participants with history of severe hypersensitivity to mAb or hypersensitivity to any of the study treatment(s) or their excipients.
• 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 investigator.
• 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.
• Receipt of transfusion of blood products (including platelets or red blood cells) or administration of colony-stimulating factors (including granulocyte colony stimulating factor [G-CSF], granulocyte-macrophage colony-stimulating factor, and recombinant erythropoietin) within 14 days before the first dose of study intervention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Part 1: Participants receiving feladilimab and ipilimumab	Drug: Feladilimab; Feladilimab will be administered.; Drug: Ipilimumab; Ipilimumab will be administered.
Experimental: Part 1: Participants receiving dostarlimab plus GSK4428859A/EOS884448/belrestotug	Drug: Dostarlimab; Dostarlimab will be administered.; Drug: GSK4428859A; GSK4428859A/EOS884448 will be administered.; Other Names: EOS884448; belrestotug
Experimental: Part 1: Participants receiving dostarlimab plus GSK4428859A/EOS884448/belrestotug plus GSK6097608	Drug: Dostarlimab; Dostarlimab will be administered.; Drug: GSK6097608; GSK6097608 will be administered.; Drug: GSK4428859A; GSK4428859A/EOS884448 will be administered.; Other Names: EOS884448; belrestotug
Active Comparator: Part 2: Participants receiving SoC: docetaxel	Drug: Docetaxel; Docetaxel will be administered.
Experimental: Part 2: Participants receiving feladilimab and docetaxel	Drug: Docetaxel; Docetaxel will be administered.; Drug: Feladilimab; Feladilimab will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants Randomized Across Sub-studies	Number of Participants randomized across sub studies are presented.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Part 1: Objective response rate	Objective response rate will be calculated as per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1 criteria. It is defined as the percentage of participants with a best overall confirmed complete response (CR) or partial response (PR) at any time as per disease-specific criteria.	Up to 2 years
Part 1: Disease control rate (DCR)	DCR is defined as the percentage of participants with a best overall confirmed CR, PR or stable disease (SD) at any time as per disease-specific criteria.	Up to 2 years
Part 1: Maximum observed concentration (Cmax) and Minimum observed concentration (Cmin) of feladilimab		Up to 2 years
Part 1: Cmax and Cmin of ipilimumab		Up to 2 years
Part 1: Cmax and Cmin of dostarlimab		Up to 2 years
Part 1: Cmax and Cmin of GSK6097608		Up to 2 years
Part 2: Survival rate at 12 and 18 months	Milestone survival rate of participants treated with experimental regimens versus SoC therapy.	At 12 and 18 months
Part 2: Number of participants with CR, Partial response (PR), Stable disease (SD) and Progressive disease (PD)	CR, PR, SD and PD will be evaluated as per RECIST version 1.1 criteria.	Up to 2 years
Part 2: Progression-free survival (PFS)	PFS is defined as time from the date of randomization to the date of disease progression or death whichever occurs earlier.	Up to 2 years
Part 2: Objective response rate (ORR)	ORR is defined as the percentage of participants with a confirmed CR or PR at any time per RECIST version 1.1 criteria.	Up to 2 years
Part 2: Duration of response (DOR)	DOR is defined as the first documented evidence of CR or PR until disease progression or death, per RECIST 1.1 criteria.	Up to 2 years
Part 2: DCR	DCR is defined as the percentage of participants with a best overall confirmed CR, PR or SD at any time as per disease-specific criteria.	Up to 2 years
Part 2: Number of participants with immune-based (i) iCR, iPR, unconfirmed progressive disease (iUPD), confirmed progressive disease (iCPD), and iSD	Number of participants with iCR, iPR, iUPD, iCPD and iSD per modified RECIST 1.1 for immune-based therapeutics (iRECIST) criteria.	Up to 2 years
Part 2: Progression-free survival (iPFS)	iPFS is defined as time from the date of randomization to the date of disease progression or death, whichever occurs earlier, per iRECIST criteria.	Up to 2 years
Part 2: Objective response rate (iORR)	iORR is defined as the percentage of participants with a confirmed CR or PR at any time per iRECIST criteria.	Up to 2 years
Part 2: Duration of response (iDOR)	iDOR is defined as the time from first documented evidence of CR or PR until disease progression or death, per iRECIST criteria.	Up to 2 years
Part 2: Number of participants with AEs, adverse events of special interest (AESI), SAEs and AE/SAEs leading to dose modifications/delays/withdrawals		Up to 2 years
Part 2: Number of participants with clinically significant changes in vital signs, physical examination and laboratory parameters		Up to 2 years
Part 2: Cmax and Cmin for SoC (docetaxel)		Up to 2 years
Part 2: Cmax and Cmin for feladilimab		Up to 2 years
Part 2: Number of participants with positive anti-drug antibodies (ADA) against docetaxel		Up to 2 years
Part 2: Number of participants with positive ADA against feladilimab		Up to 2.5 years
Part 1: Cmax and Cmin of GSK4428859A/EOS884448/belrestotug		Up to 2 years

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: iTeos Belgium SA
• Investigators: Study Director: GSK Clinical Trials, GlaxoSmithKline

Study record dates

Study Major Dates

• Study Start (Actual): January 24, 2019
• Primary Completion (Actual): May 2, 2024
• Study Completion (Actual): May 2, 2024

Study Registration Dates

• First Submitted: November 9, 2018
• First Submitted That Met QC Criteria: November 9, 2018
• First Posted (Actual): November 14, 2018

Study Record Updates

• Last Update Posted (Actual): June 15, 2025
• Last Update Submitted That Met QC Criteria: June 13, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Keywords: Docetaxel; Non-small cell lung cancer; TIGIT; Standard of care; Dostarlimab; GSK6097608; GSK4428859A; EOS884448; Anti-TIGIT; Inducible t-cell co-stimulator (ICOS); Immuno-oncology agents; Jemperli; CD-96; Anti-CD-96; belrestotug
• Additional Relevant MeSH Terms: Antineoplastic Agents, Immunological; Immune Checkpoint Inhibitors; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel; Ipilimumab; Dostarlimab
• Other Study ID Numbers: 205801; 2018-001316-29 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
• IPD Sharing Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• IPD Sharing 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.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No