Title
Platform Trial of Novel Regimens Versus Standard of Care (SoC) in Participants With Non-small Cell Lung Cancer (NSCLC) - Sub-study 1
A Phase II, Randomized, Open-label Platform Trial Utilizing a Master Protocol to Study Novel Regimens Versus Standard of Care Treatment in NSCLC Participants
Phase
Phase 2Lead Sponsor
GlaxoSmithKlineStudy Type
InterventionalStatus
Completed Results PostedIndication/Condition
NeoplasmsIntervention/Treatment
Docetaxel FeladilimabStudy Participants
105This study is a sub-study of the master protocol 205801 (NCT03739710). This sub study has assessed the clinical activity of novel regimen (Feladilimab plus Docetaxel) with SOC (Docetaxel) in participants with NSCLC.
Docetaxel was administered as IV infusion.
Feladilimab was administered as IV infusion.
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): 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.
| Event Type | Organ System | Event Term | Docetaxel 75 mg/m^2 | Feladilimab 80 mg Plus Docetaxel 75 mg/m^2 |
|---|
Overall survival was calculated as time from randomization to death. Confidence Intervals estimated using the Brookmeyer Crowley method.
Overall survival was defined as the time between date of randomization and death due to any cause. Kaplan-Meier estimates of the percentage of participants who died at each time point was calculated. Confidence Intervals estimated using the Brookmeyer Crowley method.
CR, PR, SD and PD will be evaluated as per RECIST version 1.1 criteria. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm.
PFS is defined as time from the date of randomization to the date of disease progression as per RECIST v1.1. or death whichever occurs earlier. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm. Confidence Intervals estimated using the Brookmeyer Crowley method.
ORR was calculated as the percentage of participants with a confirmed complete response (CR) or partial response (PR) relative to the total number of participants in the analysis population per response evaluation criteria in solid tumors (RECIST) version (v)1.1. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
DOR is defined as the time for first documented evidence of CR or PR until disease progression or death, per RECIST 1.1 criteria. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Confidence Intervals estimated using the Brookmeyer Crowley method.
DCR is defined as the percentage of participants with a confirmed CR + PR at any time, plus SD =>12 weeks as per RECIST v1.1. Complete Response (CR) was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. Partial Response (PR) was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). Stable Disease (SD) was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for progressive disease.
Modified RECIST 1.1 for immune-based therapeutics (iRECIST) is based on RECIST v 1.1 but adapted to account for the unique tumor response seen with immunotherapeutic drugs. iRECIST was used to assess tumor response and progression and make treatment decisions. iCR: disappearance of all target lesions; iPR: at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters (e.g. percent change from baseline). iCPD: either 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; iSD: stable disease in the absence of CR or PD and iUPD: unconfirmed progressive disease when PD is unconfirmed and NE: not evaluable.
iPFS is defined as time from the date of randomization to the date of disease progression or death, whichever occurs earlier, per iRECIST criteria. Progressive Disease was defined as at least a 20% increase in the sum of the diameters of target lesions, taking as a reference, the smallest sum of diameters recorded since the treatment started (e.g. percent change from nadir, where nadir is defined as the smallest sum of diameters recorded since treatment start). In addition, the sum must have an absolute increase from nadir of 5mm. Confidence Intervals estimated using the Brookmeyer Crowley method.
iORR is defined as the percentage of participants with a confirmed iCR or iPR at any time per iRECIST criteria. iCR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters.
iDOR is defined as the time from first documented evidence of CR or PR until disease progression or death, per iRECIST criteria. iCR was defined as disappearance of all target and non target lesions and any pathological lymph nodes must be <10 millimeter (mm) in the short axis. iPR was defined as at least a 30% decrease in the sum of the diameters of target lesions, taking as a reference, the baseline sum of the diameters. Confidence Intervals estimated using the Brookmeyer Crowley method.
An AE was defined as any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires in-patient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect, any other situation such as important medical events according to medical or scientific judgement. AESI are considered to be Infusion Related Reactions (IRRs) and those of potential immunologic etiology.
Blood samples were collected for assessment of the clinical chemistry parameters. Laboratory grades were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE. Number of participants with clinical chemistry results by maximum grade increase (Increase to Grade 3 or Increase to Grade 4) are presented.
Blood samples were collected for assessment of the hematology parameters. Laboratory grades were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE; Grade 4 = Life-threatening or disabling AE. Number of participants with Hematology results by maximum grade increase (Increase to Grade 3 or Increase to Grade 4) are presented.
Blood Pressure was measured after 5 minutes of rest and was taken in the same position throughout the study. Laboratory grades were evaluated using the Common Terminology Criteria for Adverse Events (CTCAE v5.0). Grade 1 = Mild AE; Grade 2 = Moderate AE; Grade 3 = Severe AE. Number of participants with vital signs results by maximum grade increase (Increase to Grade 2 or Increase to Grade 3) are presented.
Body temperature was measured after 5 minutes of rest. Results are presented in the following categories: Decrease to <=35 Degrees Celsius, Change to Normal or No Change and Increase to >=38 Degrees Celsius.
Pulse Rate was measured after 5 minutes of rest. Results are presented in the following categories: Decrease to <50 beats per minute, Change to Normal or No Change and Increase to >120 beats per minute.
Blood samples were collected for assessment of the pharmacokinetic parameters.
Blood samples were collected for assessment of the pharmacokinetic parameters.
Blood samples were collected for assessment of the pharmacokinetic parameters.
