A Study of Lazertinib in Participants With Epidermal Growth Factor Receptor (EGFR) Mutation Positive Advanced Non-Small Cell Lung Cancer (NSCLC)

Phase 1

Completed

Conditions: Carcinoma, Non-Small-Cell Lung

Interventions: Drug: Lazertinib

Registration Number: NCT04075396

Lead Sponsor: Janssen Research & Development, LLC

Brief Summary: The main purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics (PK) of Lazertinib when given orally to participants with epidermal growth factor receptor single activating mutation positive (EGFRm+) locally advanced or metastatic Non Small Cell Lung Cancer (NSCLC).

Detailed Description: One-third of all cancer deaths worldwide are still caused by lung cancer and non-small-cell lung cancer (NSCLC). Lazertinib is an oral, highly potent, mutant-selective and irreversible epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKIs) targets both the T790M mutation and activating EGFR mutations while sparing wild type-EGFR. The study will be conducted in participants with EGFR mutation positive advanced non-small cell lung cancer (NSCLC). Study Parts A, B, and C are sponsored by Yuhan Corporation under protocol identifier YH25448-201 (ClinicalTrials.gov Identifier: NCT03046992), and Study Part D is sponsored by Janssen Research and Development, LLC under protocol identifier 73841937NSC2001. In Part D, Lazertinib will be given to participants outside Korea, including Caucasians, in order to evaluate safety, tolerability, efficacy (including tumor response) and Pharmacokinetics (PK) in participants outside of Korea. The duration of this study will be up to 2 years. Study treatment should be held in all participants with suspected (symptomatic) or documented severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) positive disease, until recovery from all infection related symptoms, and documented to be negative for SARS-CoV-2.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 29

Inclusion Criteria

Females should agree to use adequate contraceptive measure, should not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential by fulfilling one of following criteria at screening; Post-menopausal defined as aged more than 50 years and ameorrhoeic for at least 12 months following cessation of all exogenous hormonal treatments; Documentation of irreversible surgical sterilization by hysterectomy, bilateral oophorectomy or bilateral salpingectomy but not tubal ligation; Women under 50 years old would be considered postmenopausal if they have been ameorrhoeic for at least 12 months following cessation of exogenous hormonal treatment, and have serum follicle-stimulating hormone (FSH) and luteinizing hormone (LH) levels in postmenopausal range for the institution
Male participants who have not undergone a vasectomy must agree to use barrier contraception that is, condoms, and refrain from donating sperm until 3 months after last drug is taken
During the study, and for 3 months after receiving the last dose of study drug, female participants must agree not to donate eggs (ova, oocytes) and male participants must agree not to donate sperm for the purposes of assisted reproduction
In Part D: Participants outside Korea with histologically or cytologically (that is, using pleural effusion, ascites) confirmed Non-Small Cell Lung Cancer (NSCLC) with previously diagnosed epidermal growth factor receptor single activating mutation positive (EGFRm+), and who have had progressive disease on prior epidermal growth factor receptor- Tyrosine kinase inhibitor (EGFR-TKI) therapy
Eastern Cooperative Oncology Group (ECOG) performance status 0 to 1 with no deterioration over the previous 2 weeks and a minimum life expectancy of 3 months

Exclusion Criteria

An unapproved investigational product from another clinical study within 30 days of the first dose of study treatment
Treatment with an EGFR TKIs (example: erlotinib or gefitinib) within 8 days or approximately 5x half-life, whichever is the longer, of the first dose of study treatment or other investigational products within approved indication of marketed product (if sufficient wash-out time has not occurred due to schedule or PK properties, an alternative appropriate wash-out time based on known duration of time to reversibility of drug related adverse events could be agreed upon by sponsor and the Investigator)
Any cytotoxic chemotherapy or other anticancer drugs for the treatment of advanced NSCLC from a previous treatment regimen within 14 days of the first dose of study treatment
Symptomatic spinal cord compression (if steroid treatment is not required within at least 2 weeks prior to the start of the study treatment then the participant may be enrolled)
Brain metastases with symptomatic and/or requiring emergency treatment (example; Steroid for at least 2 weeks prior to start of study treatment)

Study & Design

Study Type: INTERVENTIONAL

Study Design: SEQUENTIAL

Arm && Interventions

Group	Intervention	Description
Part D: Outside of Korea	Lazertinib	Participants from outside of Korea with progressive disease and on prior epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) therapy will receive recommended phase 2 doses based on safety, tolerability, efficacy and pharmacokinetics (PK) of Lazertinib.

Primary Outcome Measures

Name	Time	Method
Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) for Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10 and 24 hours post-dose on Day 1 of Cycle 0	AUC(0-24) was defined as area under the plasma concentration time curve from time zero to 24 hours. AUC(0-24) for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Apparent Terminal Half-Life (t1/2) for Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	T1/2 was defined the time measured for the plasma concentration of a drug to decrease by half of its initial concentration. T1/2 for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Number of Participants With Greater Than or Equal to (>=) Grade 4 Toxicity in Laboratory Tests Based on National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE) Version (v) 4.03	From Day 1 up to 14 months	Safety laboratory assessments included clinical chemistry, hematology and urinalysis. Grading was done as per NCI CTCAE version 4.03: Grade 1 = mild; Grade 2 = moderate; Grade 3 = severe; Grade 4 = life-threatening; Grade 5 = death. Baseline was defined as last non-missing measurement taken prior to reference start date.
Part D: Number of Participants With Clinically Significant Abnormalities in Electrocardiogram (ECG) Tests	From Day 1 up to 14 months	Number of participants with clinically significant abnormalities in electrocardiogram (ECG) tests were reported. ECG variables included heart rate, PR interval, RR interval, QRS interval, QT interval and Fridericia-corrected QT interval (QTcF). Baseline was defined as last non-missing measurement taken prior to reference start date.
Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-last]) for Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	AUC(0-last) was defined as area under the plasma concentration-time curve from time zero to time of last quantifiable concentration. AUC(0-last) for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS) method.
Part D: Apparent Terminal Elimination Rate Constant (Lambda[z]) for Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	Lambda(z) was defined as terminal elimination rate constant. Lambda(z) for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 15	Pre-dose on Day 15 of Cycle 1	Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 15 was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) for Multiple Dose of Lazertinib	Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2	Cmax,ss was defined as maximum observed plasma concentration at steady state. Cmax,ss for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Number of Participants With Treatment-emergent Adverse Events (TEAEs)	From Day 1 up to 14 months	An adverse event (AE) is any untoward medical occurrence in a clinical study participant administered a medicinal (investigational or non-investigational) product. An AE does not necessarily have a causal relationship with the intervention. TEAEs were defined as AEs that started on or after the first dose of study medication and prior to 28-day follow-up period. All TEAEs including serious and non-serious events are reported in this outcome measure.
Part D: Number of Participants With Clinically Significant Abnormalities in Vital Signs	From Day 1 up to 14 months	Number of participants with clinically significant abnormalities in vital signs were reported. Vital signs included pulse rate, systolic blood pressure, diastolic blood pressure, body temperature, height, weight, and body mass index (BMI). Baseline was defined as last non-missing measurement taken prior to reference start date.
Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) for Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	AUC(0-infinity) was defined as area under the plasma concentration time curve from time zero to infinite time. AUC(0-infinity) for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Apparent Plasma Clearance (CL/F) for Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	CL/F was defined as apparent plasma clearance. CL/F for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Apparent Volume of Distribution (Vd/F) for Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	Vd/F was defined as apparent volume of distribution. Vd/F for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 1	Pre-dose on Day 1 of Cycle 1	Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 1 was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Number of Participants With Clinically Significant Abnormalities in Physical Examination	From Day 1 up to 14 months	Number of participants with clinically significant abnormalities in physical examination were reported. Physical examination included general appearance, skin, head and neck (including ears, eyes, nose and throat), respiratory, cardiovascular, abdomen, lymph nodes, thyroid, muscular-skeletal (including spine and extremities) and neurological systems. Baseline was defined as last non-missing measurement taken prior to reference start date.
Part D: Maximum Observed Plasma Concentration (Cmax) for Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	Cmax was defined as maximum observed plasma concentration. Cmax for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	Tmax was defined as time to reach the maximum observed plasma concentration. Tmax for single dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the End of Dosing Interval at Steady State (AUCss[0-last]) for Multiple Dose of Lazertinib	Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2	AUCss(0-last) was defined as area under the plasma concentration time curve from time zero to end of dosing interval at steady state. AUCss(0-last) for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) for Multiple Dose of Lazertinib	Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2	Tmax,ss was defined as time to reach maximum observed plasma concentration at steady state. Tmax,ss for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Accumulation Ratio (Rac) for Multiple Dose of Lazertinib	Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2	Accumulation ratio was calculated as AUCss(0-last) divided by AUC(0-24), where AUCss(0-last) was defined as area under the plasma concentration time curve from time zero to end of dosing interval at steady state and AUC(0-24) was defined area under the plasma concentration time curve from time zero to 24 hours time. Rac for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Apparent Plasma Clearance at Steady State (CLss/F) for Multiple Dose of Lazertinib	Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2	CLss/F was defined as apparent plasma clearance at steady state. CLss/F for multiple dose of lazertinib was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Trough Concentrations (Ctrough) for Multiple Dose of Lazertinib at Cycle 1 Day 8	Pre-dose on Day 8 of Cycle 1	Ctrough was defined as pre-dose plasma concentration. Ctrough for multiple dose of lazertinib at Cycle 1 Day 8 was reported in this outcome measure. The concentrations of lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.

Secondary Outcome Measures

Name	Time	Method
Part D: Maximum Observed Plasma Concentration (Cmax) of Metabolite M7 After Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	Cmax was defined as maximum observed plasma concentration. Cmax of metabolite M7 after single dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the Last Quantifiable Concentration (AUC[0-last]) of Metabolite M7 After Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	AUC(0-last) was defined as area under the plasma concentration-time curve from time zero to time of last quantifiable concentration. AUC(0-last) of metabolite M7 after single dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Time to Reach Maximum Observed Plasma Concentration (Tmax) of Metabolite M7 After Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	Tmax was defined as time to reach the maximum observed plasma concentration. Tmax of metabolite M7 after single dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Trough Concentrations (Ctrough) of Metabolite M7 After Multiple Dose of Lazertinib at Days 1, 8 and 15 of Cycle 1	Pre-dose on Days 1, 8 and 15 of Cycle 1	Ctrough was defined as pre-dose plasma concentration. Ctrough of Metabolite M7 after multiple dose of lazertinib at Days 1, 8 and 15 of Cycle 1 was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Progression Free Survival (PFS)	Up to 33.7 months	PFS was defined as the time from the date of first dose of study drug to the earliest date of disease progression per RECIST version 1.1, or death due to any cause, whichever occurs first. PD was defined as at least 20% increase in the sum of diameters of measured lesions taking as references the smallest sum of diameters recorded on study (including baseline) and an absolute increase of \>=5 mm or appearance of at least 1 new lesion.
Part D: Area Under the Plasma Concentration Time Curve From Time Zero to 24 Hours (AUC[0-24]) of Metabolite M7 After Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10 and 24 hours post-dose on Day 1 of Cycle 0	AUC(0-24) was defined as area under the plasma concentration time curve from time zero to 24 hours. AUC(0-24) of metabolite M7 after single dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Apparent Terminal Elimination Rate Constant (Lambda [z]) of Metabolite M7 After Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	Lambda(z) was defined as terminal elimination rate constant. Lambda(z) of metabolite M7 after single dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Time to Reach Maximum Observed Plasma Concentration at Steady State (Tmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib	Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2	Tmax,ss was defined as time to reach the maximum observed plasma concentration at steady state. Tmax,ss of metabolite M7 after multiple dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Accumulation Ratio (Rac) of Metabolite M7 After Multiple Dose of Lazertinib	Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2	Accumulation ratio was calculated as AUCss(0-last) divided by AUC(0-24), where AUCss(0-last) was defined as area under the plasma concentration time curve from time zero to end of dosing interval at steady state and AUC(0-24) was defined area under the plasma concentration time curve from time zero to 24 hours. Rac of metabolite M7 after multiple dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Area Under the Plasma Concentration Time Curve From Time Zero to Infinite Time (AUC[0-Infinity]) of Metabolite M7 After Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	AUC(0-infinity) was defined as area under the plasma concentration time curve from time zero to infinite time. AUC(0-infinity) of metabolite M7 after single dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Overall Survival (OS)	Up to 33.7 months	OS was defined as the time from the date of first dose to date of death due to any cause.
Part D: Apparent Terminal Half-Life (t1/2) of Metabolite M7 After Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	T1/2 was defined the time measured for the plasma concentration of a drug to decrease by half of its initial concentration. T1/2 of metabolite M7 after single dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Maximum Observed Plasma Concentration at Steady State (Cmax,ss) of Metabolite M7 After Multiple Dose of Lazertinib	Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2	Cmax,ss was defined as maximum observed plasma concentration at steady state. Cmax,ss of metabolite M7 after multiple dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Metabolic Ratio at Steady State (MRss) of Metabolite M7 and Lazertinib After Multiple Dose of Lazertinib	Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2	MRss was defined as ratio of the AUCss(0-last) of metabolite M7 and AUCss(0-last) of lazertinib, where AUCss(0-last) was defined as area under the plasma concentration time curve from time zero to time of end of dosing interval at steady state. The concentrations of metabolite M7 and lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Percentage Change From Baseline in Tumor Size	Baseline up to 33.7 months	Tumor size was defined as the sum lengths of the longest diameters of the target lesion. Percentage change in tumor size was determined for participants with measurable disease at baseline. Baseline for RECIST version 1.1 was defined as the last evaluable assessment prior to starting treatment.
Part D: Metabolic Ratio (MR) of Metabolite M7 and Lazertinib After Single Dose of Lazertinib	Pre-dose, 1, 2, 4, 10, 24 and 48 hours post-dose on Day 1 of Cycle 0	MR was defined as ratio of the AUC(0-infinity) of metabolite M7 and AUC(0-infinity) of lazertinib, where AUC(0-infinity) was defined as area under the plasma concentration time curve from time zero to infinite time. The concentrations of metabolite M7 and lazertinib were measured using a validated, specific, and sensitive LC-MS/MS method.
Part D: Area Under the Plasma Concentration Time Curve From Time Zero to the Time of the End of Dosing Interval at Steady State (AUCss[0-last]) of Metabolite M7 After Multiple Dose of Lazertinib	Pre-dose up to 1, 2, 4, 10 and 24 hours post dose on Day 1 of Cycle 2	AUCss(0-last) was defined as area under the plasma concentration-time curve from time zero to time of the end of dosing interval at steady state. AUCss(0-last) of metabolite M7 after multiple dose of lazertinib was reported in this outcome measure. The concentrations of metabolite M7 were measured using a validated, specific, and sensitive LC-MS/MS method.
Objective Response Rate (ORR)	Up to 33.7 months	ORR was defined as percentage of participants who had at least 1 confirmed partial or complete response (PR or CR) as per Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 prior to disease progression or recurrence. CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (\<) 10 millimeter (mm). PR was defined as greater than or equal to (\>=) 30 percent (%) decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-progressive disease (PD). PD was defined as \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative 20% increase, sum must also demonstrate an absolute increase of \>=5 mm. Appearance of one or more new lesions was considered progression.
Duration of Response (DoR)	Up to 33.7 months	DOR was defined as time between date of first documented confirmed response (PR/CR) and date of first documented progression or death, whichever occurred first. CR was defined as disappearance of target and non-target lesions and normalization of tumour markers. Pathological lymph nodes short axis measures \<10 mm. PR was defined as \>=30% decrease in sum of measures (tumour lesions-longest diameter and nodes-short axis)of target lesions, taking as reference baseline sum of diameters. PD was defined as \>=20% increase in sum of diameters of measured lesions taking as references smallest sum of diameters recorded on study(including baseline), absolute increase of \>=5 mm/appearance of at least 1 new lesion. Unequivocal progression of existing non-target lesions.
Disease Control Rate (DCR)	Up to 33.7 months	DCR was defined as percentage of participants with a best overall response (BOR), extracranial and intracranial response of CR, PR or stable disease (SD). As per RECIST version 1.1 CR was defined as disappearance of target and non-target lesions and normalization of tumor markers. Pathological lymph nodes must have short axis measures \<10 mm. PR was defined as \>=30% decrease in sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of target lesions, taking as reference baseline sum of diameters. Non-target lesions must be non-PD. PD was defined as \>=20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative 20% increase, sum must also demonstrate \>=5 mm absolute increase. Appearance of one or more new lesions was considered progression. SD was defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD.

Trial Locations

Locations (9): City of Hope
🇺🇸
Duarte, California, United States
Advent Health Orlando
🇺🇸
Orlando, Florida, United States
Hosp. Gral. Univ. Gregorio Maranon
🇪🇸
Madrid, Spain
Hosp Virgen de La Victoria
🇪🇸
Malaga, Spain
Moffitt Cancer Center
🇺🇸
Tampa, Florida, United States
Montefiore Medical Center
🇺🇸
Bronx, New York, United States
Tennessee Oncology
🇺🇸
Nashville, Tennessee, United States
Hosp Univ Vall D Hebron
🇪🇸
Barcelona, Spain
The Christie Nhs Foundation Trust
🇬🇧
Manchester, United Kingdom