A Study of Amivantamab and Lazertinib in Combination With Platinum-Based Chemotherapy Compared With Platinum-Based Chemotherapy in Patients With Epidermal Growth Factor Receptor (EGFR)-Mutated Locally Advanced or Metastatic Non- Small Cell Lung Cancer After Osimertinib Failure
Lazertinib: Lazertinib will be administered orally.
Amivantamab: Amivantamab will be administered as an IV infusion.
Pemetrexed: Pemetrexed will be administered as an IV infusion.
Carboplatin: Carboplatin will be administered as an IV infusion.
Study summary
The purpose of this study is to assess the efficacy of adding lazertinib to amivantamab, carboplatin, and pemetrexed (LACP/ACP-L dosing strategies) and amivantamab, carboplatin and pemetrexed (ACP) compared with carboplatin and pemetrexed (CP) in participants with locally advanced or metastatic epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R substitution non-small cell lung cancer (NSCLC) after osimertinib failure. The purpose of the extension cohort is to further describe the safety and efficacy for the ACP-L dosing schedule versus ACP with additional data. After completion of the primary analysis, the study may eventually transition to an open-label extension (OLE) or long-term extension (LTE) phase during which participants will have the option to continue their assigned treatment.
Eligibility
Sex
ALL
Min age
18 Years
Max age
—
Healthy volunteers
No
Inclusion Criteria:
* Participant must have at least 1 measurable lesion, according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1, that has not been previously irradiated
* Participant must have histologically or cytologically confirmed, locally advanced or metastatic, non-squamous non-small cell lung cancer (NSCLC), characterized at or after the time of locally advanced or metastatic disease diagnosis by either epidermal growth factor receptor (EGFR) Exon 19del or Exon 21 L858R mutation
* A participant with a history of brain metastases must have had all lesions treated as clinically indicated (that is, no current indication for further definitive local therapy). Any definitive local therapy to brain metastases must have been completed at least 14 days prior to randomization and the participant can be receiving no greater than10 milligrams (mg) prednisone or equivalent daily for the treatment of intracranial disease
* Participant must have Eastern Cooperative Oncology Group (ECOG) status of 0 or 1
* Any toxicities from prior systemic anticancer therapy must have resolved to National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Version 5.0 Grade 1 or baseline level (except for alopecia \[any grade\], Grade \<= 2 peripheral neuropathy, or Grade \<= 2 hypothyroidism stable on hormone replacement)
* A participant of childbearing potential must have a negative serum pregnancy test at screening and within 72 hours of the first dose of study treatment and must agree to further serum or urine pregnancy tests during the study
* Participant must have progressed on or after osimertinib monotherapy as the most recent line of treatment. Osimertinib must have been administered as either the first-line treatment for locally advanced or metastatic disease or in the second- line setting after prior treatment with first- or second-generation EGFR tyrosine kinase inhibitor (TKI) as a monotherapy. Participants who received either neoadjuvant and/or adjuvant treatment of any type are eligible if progression to locally advanced or metastatic disease occurred at least 12 months after the last dose of such therapy and then the participant progressed on or after osimertinib in the locally advanced or metastatic setting. Treatment with osimertinib must be discontinued at least 8 days (4 half-lives) prior to randomization (that is last dose no later than Day -8)
Exclusion Criteria:
* Participant received radiotherapy for palliative treatment of NSCLC less than 14 days prior to randomization
* Participant with symptomatic or progressive brain metastases
* Participant has history of or current evidence of leptomeningeal disease, or participant has spinal cord compression not definitively treated with surgery or radiation
* Participant has known small cell transformation
* Participant has a medical history of interstitial lung disease (ILD), including drug-induced ILD or radiation pneumonitis
* Participant has a history of clinically significant cardiovascular disease including, but not limited to diagnosis of deep vein thrombosis or pulmonary embolism within 4 weeks prior to randomization; myocardial infarction; unstable angina; stroke; transient ischemic attack; coronary/peripheral artery bypass graft; or acute coronary syndrome. Participant has a significant genetic predisposition to venous thromboembolic events. Participant has a prior history of venous thromboembolic events and is not on appropriate therapeutic anticoagulation as per National Comprehensive Cancer Network or local guidelines
Primary outcome measure(s)
Main Study: Progression-free Survival (PFS) According to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 as Assessed by Blinded Independent Central Review (BICR) — From randomization to either disease progression or death, whichever occurred first (up to 1 year 7 months) PFS is defined as the time from randomization until the date of objective disease progression or death, whichever came first, as assessed by BICR according to RECIST version 1.1. Progressed disease: Sum of diameters increased by greater than or equal to (\>=)20 percent (%) and \>=5 millimeter (mm) from nadir (including baseline if it was smallest sum).
Main Study + Extension Cohort: Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) — up to 4 years 10 months Follow-up for the extension cohort is still ongoing and thus results from the analysis that includes the extension cohort will be reported up on study completion.
Main Study + Extension Cohort: Progression-free Survival (PFS) as Assessed by Blinded Independent Central Review — Up to 4 years 10 months
Trial sites (249)
Facility
City
Region
Status
Southern Cancer Center, PC
Mobile
Alabama
Arizona Oncology Associates
Tucson
Arizona
City of Hope
Duarte
California
Cedars Sinai Medical Center
Los Angeles
California
University of California Irvine
Orange
California
Rocky Mountain Cancer Centers
Colorado Springs
Colorado
Holy Cross Hospital - Michael and Dianne Bienes Comprehensive Cancer Center
Fort Lauderdale
Florida
University Cancer And Blood Center LLC
Athens
Georgia
University of Mississippi Medical Center
Jackson
Mississippi
Nebraska Cancer Specialists
Grand Island
Nebraska
Astera Cancer Care
East Brunswick
New Jersey
TriHealth Network
Cincinnati
Ohio
Providence Portland Medical Center
Portland
Oregon
Kaiser Permanente Northwest
Portland
Oregon
Alliance Cancer Specialists
Horsham
Pennsylvania
University of Pittsburgh Medical Center
Pittsburgh
Pennsylvania
Baptist Cancer Center
Memphis
Tennessee
Texas Oncology-Medical City Dallas
Dallas
Texas
Texas Oncology Baylor Charles A Sammons Cancer Center
Dallas
Texas
Texas Oncology
Grapevine
Texas
Oncology Consultants Texas
Houston
Texas
Texas Oncology - Northeast
Longview
Texas
University of Vermont Medical Center
Burlington
Vermont
University of Virginia
Charlottesville
Virginia
Virginia Cancer Specialists
Fairfax
Virginia
Blue Ridge Cancer Care
Wytheville
Virginia
NorthWest Medical Specialties, PLLC
Puyallup
Washington
Compass Oncology
Vancouver
Washington
CINME Centro de Investigaciones Metabolicas
Caba
Argentina
IADT Instituto Argentino de Diagnostico y Tratamiento
CABA
Argentina
Centro Medico Fleischer
CABA
Argentina
CEMIC (Centro de Educación Médica e Investigaciones Clínicas)
CABA
Argentina
Cemaic Centro Privado de Especialidades Medicas Ambulatorias e Investigacion Clinica
Córdoba
Argentina
Hospital Privado Universitario De Cordoba
Córdoba
Argentina
Hospital Privado de la Comunidad
Mar del Plata
Argentina
Clínica Viedma
Viedma
Argentina
Grand Hopital De Charleroi Site Les Viviers
Charleroi
Belgium
UZA
Edegem
Belgium
UZ Gent
Ghent
Belgium
Jessa Ziekenhuis - Campus Virga Jesse
Hasselt
Belgium
+ 209 more sites — see the full list on the official registry below.
More Janssen Research & Development, LLC trials in the UK
This page summarises publicly available registry data for informational purposes — not medical advice. Eligibility is determined by each study team; patients should discuss participation with their clinician.
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