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

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: Recruiting

Administrative data

• NCT number: NCT03739710
• Other study ID #: 205801
• Secondary ID: 2018-001316-29
• Status: Recruiting
• Phase: Phase 2
• Start date: January 24, 2019
• Est. completion date: July 8, 2025

Study information

• Verified date: June 2023
• Source: GlaxoSmithKline
• Contact: US GSK Clinical Trials Call Center
• Phone: 877-379-3718
• Email: GSKClinicalSupportHD[@]gsk.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 185
• Est. completion date: July 8, 2025
• Est. primary completion date: July 8, 2025
• 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. 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.

Related Conditions & MeSH terms

• Neoplasms

Intervention

Drug:
• Docetaxel
Docetaxel will be administered.
• Feladilimab
Feladilimab will be administered.
• Ipilimumab
Ipilimumab will be administered.
• GSK4428859A
GSK4428859A/EOS884448 will be administered.
• Dostarlimab
Dostarlimab will be administered.
• GSK6097608
GSK6097608 will be administered.

Locations

Country	Name	City	State
Canada	GSK Investigational Site	Brampton	Ontario
Canada	GSK Investigational Site	Edmonton	Alberta
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	Heidelberg	Baden-Wuerttemberg
Germany	GSK Investigational Site	Immenhausen	Hessen
Germany	GSK Investigational Site	Kassel	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	Napoli	Campania
Italy	GSK Investigational Site	Orbassano (TO)	Piemonte
Italy	GSK Investigational Site	Ravenna	Emilia-Romagna
Italy	GSK Investigational Site	Siena	Toscana
Korea, Republic of	GSK Investigational Site	Cheongju-si, Chungcheongbuk-do
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	Amsterdam
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	Badajoz
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	Málaga
Spain	GSK Investigational Site	Santander
Spain	GSK Investigational Site	Sevilla
Sweden	GSK Investigational Site	Solna
Sweden	GSK Investigational Site	Uppsala
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Bronx	New York
United States	GSK Investigational Site	Chattanooga	Tennessee
United States	GSK Investigational Site	Dallas	Texas
United States	GSK Investigational Site	Los Angeles	California
United States	GSK Investigational Site	Nashville	Tennessee
United States	GSK Investigational Site	Pinehurst	North Carolina
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	Part 1: Number of participants with any adverse events (AEs) and serious adverse events (SAEs)		Up to 2 years
Primary	Part 1: Number of participants with dose limiting toxicity (DLT)		Up to 2 years
Primary	Part 1: Number of participants with clinically significant changes in vital signs, physical examination and laboratory parameters		Up to 2 years
Primary	Part 1: Number of participants requiring dose modifications		Up to 2 years
Primary	Part 2: Overall survival	Overall survival will be calculated as time from randomization to death.	Up to 3 years
Secondary	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
Secondary	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
Secondary	Part 1: Maximum observed concentration (Cmax) and Minimum observed concentration (Cmin) of feladilimab		Up to 2 years
Secondary	Part 1: Cmax and Cmin of ipilimumab		Up to 2 years
Secondary	Part 1: Cmax and Cmin of GSK4428859A/EOS884448/belrestotug		Up to 2 years
Secondary	Part 1: Cmax and Cmin of dostarlimab		Up to 2 years
Secondary	Part 1: Cmax and Cmin of GSK6097608		Up to 2 years
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Part 2: Number of participants with clinically significant changes in vital signs, physical examination and laboratory parameters		Up to 2 years
Secondary	Part 2: Cmax and Cmin for SoC (docetaxel)		Up to 2 years
Secondary	Part 2: Cmax and Cmin for feladilimab		Up to 2 years
Secondary	Part 2: Number of participants with positive anti-drug antibodies (ADA) against docetaxel		Up to 2 years
Secondary	Part 2: Number of participants with positive ADA against feladilimab		Up to 2.5 years