Non-small Cell Lung Cancer MedDRA version: 21.1 Level: PT Classification code 10059515 Term: Non-small cell lung cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
GlaxoSmithKline Research & Development Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Key Inclusion Criteria 1. Is capable of giving signed informed consent 2. Is, at the time of signing the ICF, at least 18 years old or the legal age of consent in the jurisdiction in which the study is taking place. 3. Has a histologically or cytologically confirmed diagnosis of locally advanced unresectable NSCLC not eligible for curative surgery and/or definitive radiotherapy with or without chemotherapy or metastatic NSCLC (squamous or nonsquamous). Mixed tumors will be categorized by the predominant cell type; if small cell or neuroendocrine elements are present, the participant is ineligible. 4. Has not received prior systemic therapy for their locally advanced or metastatic NSCLC. NOTE: Completion of treatment with cytotoxic chemotherapy and/or radiation as part of neoadjuvant/adjuvant therapy is allowed if therapy was completed at least 6 months prior to the diagnosis of locally advanced or metastatic disease. Prior treatment with neoadjuvant/adjuvant immunotherapy is not permitted. 5. Has a PD-L1-high tumor 6. Has measurable disease based on RECIST 1.1 (Appendix 7), as determined by the investigator. 7. Has an ECOG PS 0 or 1. 8. Has adequate organ function 9. If of childbearing potential, female participants must be willing to use adequate contraception. Refer protocol for other inclusion criteria Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 165 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 135
Exclusion criteria
Exclusion criteria: Key Exclusion criteria 1. Has NSCLC with a tumor that harbors any of the following molecular alterations: a. EGFR mutations that are sensitive to available targeted inhibitor therapy b. ALK translocations that are sensitive to available targeted inhibitor therapy. c. Any other known genomic aberrations or oncogenic driver mutations for which a locally approved targeted therapy is available for first line treatment of locally advanced or metastatic NSCLC. 2. Has had major surgery within 4 weeks of the first dose of study intervention or has received lung radiation therapy of >30 Gy within 6 months of the first dose of study intervention. 3. Has received prior therapy with any immune checkpoint inhibitors, including antibodies or drugs targeting PD-1, PD-L1, CTLA-4, TIGIT, CD96, or other checkpoint pathways. 4. Has never smoked, defined as smoking 470 msec, or >480 msec for participants with bundle branch block. QTcF is QT corrected for heart rate according to Fridericia’s formula and can be machine calculated or manually over-read. 13. Has active tuberculosis (i.e., history of exposure or history of positive tuberculosis test, plus presence of clinical symptoms or physical or radiographic findings). 14. Has a known human immunodeficiency virus infection. 15. Has a history of severe hypersensitivity to mAbs or to any of the excipients in the formulations of the components of the study interventions. 16. Has a positive test for the presence of HBsAg at Screening or within 3 months prior to first dose of study intervention. 17. Has a positive hepatitis C antibody test result at Screening or within 3 months prior to first dose of study intervention. NOTE: Participants with a positive hepatitis C antibody test due to prior resolved disease can be enrolled only if a confirmatory negative hepatitis C RNA test is obtained. 18. Has a positive hepatitis C RNA test result at Screening or within 3 months prior to first dose of study intervention. NOTE: Participants with a negative hepatitis C antibody test are not required to also undergo hepatitis C RNA testing. Refer protocol for other exclusion criteria
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: • To evaluate the antitumor activity of novel immunotherapy combinations compared with pembrolizumab in participants with PD-L1 high (TC/TPS =50%) NSCLC;Secondary Objective: • To assess the dose response relationship of novel immunotherapy combinations across a range of the novel components' dose levels and fixed dostarlimab dose (may not apply to all novel combinations) • To further assess the clinical activity of novel immunotherapy combinations compared with pembrolizumab in participants with PD-L1 high (TC/TPS =50%) • To evaluate the antitumor activity of novel immunotherapy combinations via treatment arm comparisons for assessment of contribution of components for the combination regimens • To further characterize the safety of novel immunotherapy combinations • To determine the immunogenicity of individual agents comprising novel immunotherapy combinations • To characterize the PK properties of novel immunotherapy combinations ;Primary end point(s): • ORR per RECIST 1.1 by investigator assessment;Timepoint(s) of evaluation of this end point: • every 6 weeks after randomization until week 25, every 9 weeks until week 52, and every 12 weeks thereafter until RECIST 1.1 defined PD." | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • ORR per RECIST v1.1 by investigator assessment at different dose levels • PFS per RECIST 1.1 by investigator assessment • OS • DOR per RECIST 1.1 by investigator assessment • ORR, PFS, and DOR per RECIST 1.1 by investigator assessment, and OS for assessment of contribution of components for the combination regimens • Incidence of TEAEs, SAEs and AESI • Incidence of TEAEs/SAEs leading to dose modifications or study intervention discontinuation • Incidence of ADA • Plasma PK parameters ;Timepoint(s) of evaluation of this end point: • ORR: Every 6 weeks after randomization until week 25, every 9 weeks until week 52, and every 12 weeks thereafter until RECIST 1.1 defined PD." • PFS: The time from the date of randomization to the date of first documented PD per RECIST 1.1 by investigator assessment, or death by any cause, whichever occurs first • OS: Following treatment discontinuation, survival status will be assessed every 12 weeks after the last dose of study intervention, until death or participant’s withdrawal • DOR: Time from the date of first documented CR or PR until the date of first documented PD per RECIST 1.1 All SAEs and AESI, Plasma PK parameters, Incidence of ADA will be collected throughout the study as per protocol Refer protocol for other timepoints | — |
Countries
Argentina, Belgium, Brazil, Finland, France, Germany, Greece, Hungary, Italy, Japan, Korea, Republic of, Mexico, Netherlands, Poland, Portugal, South Africa, Spain, Thailand, Türkiye, United Kingdom, United States
Contacts
Public ContactClinical Trials Helpdesk Support
GlaxoSmithKline Research & Development Ltd
Outcome results
None listed