Platform Trial of Novel Regimens Versus Standard of Care (SoC) in Participants With Non-small Cell Lung Cancer (NSCLC) - Sub-study 1

Neoplasms Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05553808
• Other study ID #: 205801-001
• Secondary ID: 2018-001316-29
• Status: Completed
• Phase: Phase 2
• Start date: January 24, 2019
• Est. completion date: September 23, 2021

Study information

• Verified date: December 2022
• Source: GlaxoSmithKline
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 105
• Est. completion date: September 23, 2021
• Est. primary completion date: September 23, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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. 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.

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Docetaxel
Docetaxel was administered as IV infusion.
• Feladilimab
Feladilimab was administered as IV infusion.

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Toronto	Ontario
France	GSK Investigational Site	Bordeaux Cedex
France	GSK Investigational Site	Caen Cedex 9
France	GSK Investigational Site	Nantes cedex 1
France	GSK Investigational Site	Paris
France	GSK Investigational Site	Paris Cedex 05
France	GSK Investigational Site	Villejuif Cedex
Germany	GSK Investigational Site	Berlin
Germany	GSK Investigational Site	Gauting	Bayern
Germany	GSK Investigational Site	Grosshansdorf	Schleswig-Holstein
Germany	GSK Investigational Site	Immenhausen	Hessen
Germany	GSK Investigational Site	Leipzig	Sachsen
Italy	GSK Investigational Site	Meldola (FC)	Emilia-Romagna
Italy	GSK Investigational Site	Milano	Lombardia
Italy	GSK Investigational Site	Orbassano (TO)	Piemonte
Italy	GSK Investigational Site	Ravenna	Emilia-Romagna
Korea, Republic of	GSK Investigational Site	Cheongju-si
Korea, Republic of	GSK Investigational Site	Gyeonggi-do
Korea, Republic of	GSK Investigational Site	Seongnam
Korea, Republic of	GSK Investigational Site	Seoul
Netherlands	GSK Investigational Site	Maastricht
Poland	GSK Investigational Site	Lodz
Poland	GSK Investigational Site	Poznan
Poland	GSK Investigational Site	Warszawa
Romania	GSK Investigational Site	Bucharest
Romania	GSK Investigational Site	Craiova
Romania	GSK Investigational Site	Floresti
Romania	GSK Investigational Site	Otopeni
Romania	GSK Investigational Site	Timisoara
Russian Federation	GSK Investigational Site	Chelyabinsk
Russian Federation	GSK Investigational Site	Saint-Petersburg
Russian Federation	GSK Investigational Site	Saint-Petersburg
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Barcelona
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Madrid
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Sevilla
Sweden	GSK Investigational Site	Uppsala
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	Saint Louis	Missouri

Sponsors (2)

Lead Sponsor	Collaborator
GlaxoSmithKline	iTeos Belgium SA

Countries where clinical trial is conducted

United States,  Canada,  France,  Germany,  Italy,  Korea, Republic of,  Netherlands,  Poland,  Romania,  Russian Federation,  Spain,  Sweden, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival	Overall survival was calculated as time from randomization to death. Confidence Intervals estimated using the Brookmeyer Crowley method.	Up to 2 years
Secondary	Kaplan-Meier Estimates of Overall Survival at 12 and 18 Months	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.	Month 12 and 18
Secondary	Number of Participants With Complete Response (CR), Partial Response (PR), Stable Disease (SD), Progressive Disease (PD) or Not Evaluable	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.	Up to 2 years
Secondary	Kaplan-Meier Estimates of Progression-Free Survival (PFS)	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.	Up to 2 years
Secondary	Objective Response Rate	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.	Up to 2 years
Secondary	Kaplan-Meier Estimates of Duration of Response (DOR) in Participants With Objective Response	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.	Up to 2 years
Secondary	Disease Control Rate (DCR)	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.	Up to 2 years
Secondary	Number of Participants With iRECIST Complete Response (iCR), Partial Response (iPR), Unconfirmed Progressive Disease (iUPD), Confirmed Progressive Disease (iCPD), Stable Disease (iSD) or Not Evaluable	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.	Up to 2 years
Secondary	Kaplan-Meier Estimates of iRECIST 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. 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.	Up to 2 years
Secondary	iRECIST Objective Response Rate (iORR)	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.	Up to 2 years
Secondary	Kaplan-Meier Estimates of iRECIST Duration of Response (iDOR) in Participants With Objective Response	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.	Up to 2 years
Secondary	Number of Participants With AEs, Adverse Events of Special Interest (AESI), SAEs and AE/SAEs Leading to Dose Modifications/Delays/Withdrawals	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.	Up to 2 years
Secondary	Number of Participants With Maximum Grade Increase in Clinical Chemistry Parameters at Worst Case Post-Baseline	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.	Up to 2 years
Secondary	Number of Participants With Maximum Grade Increase in Hematology Parameters at Worst Case Post-Baseline	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.	Up to 2 years
Secondary	Number of Participants With Maximum Grade Increase in Vital Signs (Systolic Blood Pressure and Diastolic Blood Pressure) Parameters at Worst Case Post-Baseline	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.	Up to 2 years
Secondary	Number of Participants With Vital Signs (Temperature) Parameter Results at Worst Case Post-Baseline	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.	Up to 2 years
Secondary	Number of Participants With Vital Signs (Pulse Rate) Parameter Results at Worst Case Post-Baseline	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.	Up to 2 years
Secondary	Minimum Observed Concentration (CmIn) of Feladilimab	Blood samples were collected for assessment of the pharmacokinetic parameters.	Week 1
Secondary	Maximum Observed Concentration (Cmax) of Feladilimab	Blood samples were collected for assessment of the pharmacokinetic parameters.	Week 1, Week 13 and Week 25
Secondary	Maximum Observed Concentration (Cmax) of Docetaxel	Blood samples were collected for assessment of the pharmacokinetic parameters.	Week 1, Week 4, Week 7, Week 10, Week 13, Week 16, Week 19 and Week 22
Secondary	Number of Participants With Positive Anti-drug Antibodies (ADA) Against Docetaxel		Up to 2 years
Secondary	Number of Participants With Positive ADA Against Feladilimab		Week 1, 4, 7, 10, 13, 16, 19, 22, 25, 37, 49, 61 and 73