Platform Trial of Novel Regimens Versus Standard of Care (SoC) in Participants With Non-small Cell Lung Cancer (NSCLC)
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|ClinicalTrials.gov Identifier: NCT03739710|
Recruitment Status : Recruiting
First Posted : November 14, 2018
Last Update Posted : November 8, 2022
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|Condition or disease||Intervention/treatment||Phase|
|Neoplasms||Drug: Docetaxel Drug: Feladilimab Drug: Ipilimumab Drug: GSK4428859A/EOS884448 Drug: Dostarlimab Drug: GSK6097608||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||185 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Masking Description:||The study will be open-label.|
|Official Title:||A Phase II, Randomized, Open-label Platform Trial Utilizing a Master Protocol to Study Novel Regimens Versus Standard of Care Treatment in NSCLC Participants|
|Actual Study Start Date :||January 24, 2019|
|Estimated Primary Completion Date :||July 8, 2025|
|Estimated Study Completion Date :||July 8, 2025|
|Experimental: Part 1: Participants receiving feladilimab and ipilimumab||
Feladilimab will be administered.
Ipilimumab will be administered.
|Experimental: Part 1: Participants receiving dostarlimab plus GSK4428859A/EOS884448||
GSK4428859A/EOS884448 will be administered.
Dostarlimab will be administered.
|Experimental: Part 1: Participants receiving dostarlimab plus GSK4428859A/EOS884448 plus GSK6097608||
GSK4428859A/EOS884448 will be administered.
Dostarlimab will be administered.
GSK6097608 will be administered.
|Active Comparator: Part 2: Participants receiving SoC: docetaxel||
Docetaxel will be administered.
|Experimental: Part 2: Participants receiving feladilimab and docetaxel||
Docetaxel will be administered.
Feladilimab will be administered.
- Part 1: Number of participants with any adverse events (AEs) and serious adverse events (SAEs) [ Time Frame: Up to 2 years ]
- Part 1: Number of participants with dose limiting toxicity (DLT) [ Time Frame: Up to 2 years ]
- Part 1: Number of participants with clinically significant changes in vital signs, physical examination and laboratory parameters [ Time Frame: Up to 2 years ]
- Part 1: Number of participants requiring dose modifications [ Time Frame: Up to 2 years ]
- Part 2: Overall survival [ Time Frame: Up to 3 years ]Overall survival will be calculated as time from randomization to death.
- Part 1: Objective response rate [ Time Frame: Up to 2 years ]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.
- Part 1: Disease control rate (DCR) [ Time Frame: Up to 2 years ]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.
- Part 1: Maximum observed concentration (Cmax) and Minimum observed concentration (Cmin) of feladilimab [ Time Frame: Up to 2 years ]
- Part 1: Cmax and Cmin of ipilimumab [ Time Frame: Up to 2 years ]
- Part 1: Cmax and Cmin of GSK4428859A/EOS884448 [ Time Frame: Up to 2 years ]
- Part 1: Cmax and Cmin of dostarlimab [ Time Frame: Up to 2 years ]
- Part 1: Cmax and Cmin of GSK6097608 [ Time Frame: Up to 2 years ]
- Part 2: Survival rate at 12 and 18 months [ Time Frame: At 12 and 18 months ]Milestone survival rate of participants treated with experimental regimens versus SoC therapy.
- Part 2: Number of participants with CR, Partial response (PR), Stable disease (SD) and Progressive disease (PD) [ Time Frame: Up to 2 years ]CR, PR, SD and PD will be evaluated as per RECIST version 1.1 criteria.
- Part 2: Progression-free survival (PFS) [ Time Frame: Up to 2 years ]PFS is defined as time from the date of randomization to the date of disease progression or death whichever occurs earlier.
- Part 2: Objective response rate (ORR) [ Time Frame: Up to 2 years ]ORR is defined as the percentage of participants with a confirmed CR or PR at any time per RECIST version 1.1 criteria.
- Part 2: Duration of response (DOR) [ Time Frame: Up to 2 years ]DOR is defined as the first documented evidence of CR or PR until disease progression or death, per RECIST 1.1 criteria.
- Part 2: DCR [ Time Frame: Up to 2 years ]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.
- Part 2: Number of participants with immune-based (i) iCR, iPR, unconfirmed progressive disease (iUPD), confirmed progressive disease (iCPD), and iSD [ Time Frame: Up to 2 years ]Number of participants with iCR, iPR, iUPD, iCPD and iSD per modified RECIST 1.1 for immune-based therapeutics (iRECIST) criteria.
- Part 2: Progression-free survival (iPFS) [ Time Frame: Up to 2 years ]iPFS is defined as time from the date of randomization to the date of disease progression or death, whichever occurs earlier, per iRECIST criteria.
- Part 2: Objective response rate (iORR) [ Time Frame: Up to 2 years ]iORR is defined as the percentage of participants with a confirmed CR or PR at any time per iRECIST criteria.
- Part 2: Duration of response (iDOR) [ Time Frame: Up to 2 years ]iDOR is defined as the time from first documented evidence of CR or PR until disease progression or death, per iRECIST criteria.
- Part 2: Number of participants with AEs, adverse events of special interest (AESI), SAEs and AE/SAEs leading to dose modifications/delays/withdrawals [ Time Frame: Up to 2 years ]
- Part 2: Number of participants with clinically significant changes in vital signs, physical examination and laboratory parameters [ Time Frame: Up to 2 years ]
- Part 2: Cmax and Cmin for SoC (docetaxel) [ Time Frame: Up to 2 years ]
- Part 2: Cmax and Cmin for feladilimab [ Time Frame: Up to 2 years ]
- Part 2: Number of participants with positive anti-drug antibodies (ADA) against docetaxel [ Time Frame: Up to 2 years ]
- Part 2: Number of participants with positive ADA against feladilimab [ Time Frame: Up to 2.5 years ]
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
|Ages Eligible for Study:||18 Years and older (Adult, Older Adult)|
|Sexes Eligible for Study:||All|
|Accepts Healthy Volunteers:||No|
- 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.
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):
- Docetaxel at any time.
- Any of the investigational agents being tested in the current study.
- 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 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:
- Greater than or equal to (>=) 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.
- 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, 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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03739710
|Contact: US GSK Clinical Trials Call Center||877-379-3718||GSKClinicalSupportHD@gsk.com|
|Contact: EU GSK Clinical Trials Call Center||+44 (0) 20 89904466||GSKClinicalSupportHD@gsk.com|
|Study Director:||GSK Clinical Trials||GlaxoSmithKline|
|Other Study ID Numbers:||
|First Posted:||November 14, 2018 Key Record Dates|
|Last Update Posted:||November 8, 2022|
|Last Verified:||November 2022|
|Individual Participant Data (IPD) Sharing Statement:|
|Plan to Share IPD:||Yes|
|Plan Description:||IPD for this study will be made available via the Clinical Study Data Request site.|
Statistical Analysis Plan (SAP)
Informed Consent Form (ICF)
Clinical Study Report (CSR)
|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.|
|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.|
|Studies a U.S. FDA-regulated Drug Product:||Yes|
|Studies a U.S. FDA-regulated Device Product:||No|
Non-small cell lung cancer
Inducible t-cell co-stimulator (ICOS)
Standard of care
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological
Immune Checkpoint Inhibitors