Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| NCT03909971 | Registry Identifier | ClinicalTrials.gov |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
A Phase 2, multi center, open label, dual cohort study to evaluate the efficacy and safety of lorlatinib (PF 06463922) monotherapy in ALK inhibitor treated locally advanced or metastatic ALK positive non small cell lung cancer patients in China
This is a Phase 2, China only, multi center, open label, dual cohort study, in ALK positive locally advanced or metastatic NSCLC patients will be enrolled to receive lorlatinib monotherapy.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Lorlatinib | Experimental | Lorlatinib single agent, 100 mg (4 x 25 mg) oral tables, QD, continuously |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Lorlatinib | Drug | ALK inhibitor-treated ALK-positive NSCL treatment |
|
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Objective Response (Cohort 1) | Objective response rate (ORR) was defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 relative to the total participants in the analysis population. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR was defined as a greater than equal to (>=) 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Independent Central Radiology (ICR) was used for disease progression assessment. | From Cycle 1 Day 1 to documented progression of disease by ICR (up to 67 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Objective Response (Cohort 2) | ORR was defined as the percentage of participants with a best overall confirmed response of CR or PR according to RECIST version 1.1 relative to the total participants in the analysis population. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. ICR was used for disease progression assessment. |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants With Objective Response (Cohort 1)-Final Analysis | ORR was defined as the percentage of participants with a best overall confirmed response of CR or PR according to RECIST version 1.1 relative to the total participants in the analysis population. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. ICR was used for disease progression assessment. |
Inclusion Criteria:
Evidence of histologically or cytologically confirmed diagnosis of locally advanced or metastatic ALK positive NSCLC where ALK status has been previously established by the Ventana ALK (D5F3) CDx Assay (Roche Diagnostics), the Vysis ALK Break Apart FISH Probe Kit (Abbott Molecular), or the EML4 ALK Fusion Gene Detection Kit (AmoyDx).
Subject should have:
Prior treatment with an ALK inhibitor must have completed 5 half lives prior to study entry.
All Subjects must have at least 1 measurable extracranial target lesion according to RECIST v1.1 that has not been previously irradiated. CNS metastases are allowed if:
Eastern Cooperative Oncology Group performance status (ECOG PS) 0, 1, or 2.
Age 18 years (or 20 years as required by local regulation).
Adequate bone marrow functions:
Adequate pancreatic function:
Adequate renal function:
a. Serum creatinine 1.5 x ULN or estimated creatinine clearance 60 mL/min as calculated using the method standard for the institution.
Adequate liver function:
Acute effects of prior radiotherapy and chemotherapy resolved to baseline severity or to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) Grade 1 except for AEs that in the investigator's judgment do not constitute a safety risk for the subject.
Serum or urine pregnancy test (for females of childbearing potential) negative at screening. Female subjects of non childbearing potential must meet at least 1 of the following criteria:
Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative) has been informed of all pertinent aspects of the study.
Willing and able to comply with the study scheduled visits, treatment plans, laboratory tests, and other procedures.
Exclusion Criteria:
Subjects with any of the following characteristics/conditions will not be included in the study:
More than 1 prior chemotherapy regimen prior to enrollment in advanced/metastatic setting.
If disease recurred/relapsed within the adjuvant chemotherapy treatment or <=6 months after the completion of the adjuvant chemotherapy, then the adjuvant chemotherapy is considered as the first line systemic chemotherapy to the disease.
Systemic anti cancer therapy completed within a minimum of 5 half lives of study enrollment.
Prior therapy with an antibody or drug specifically targeting T cell co stimulation or immune checkpoint pathways, including, but not limited to, anti programmed cell death protein 1 (anti PD 1), anti programmed cell death protein ligand 1 (anti PD L1), anti PD L2, anti cluster of differentiation 137 (anti CD137), or anti cytotoxic T lymphocyte associated antigen 4 (anti CTLA 4) antibody.
Known epidermal growth factor receptor (EGFR) activating mutations; known prior therapy with EGFR TKI(s) (the prior treatment with brigatinib is allowed as an ALK TKI).
Major surgery within 4 weeks prior to enrollment. Minor surgical procedures (eg, port insertion) are not excluded, but sufficient time should have passed for adequate wound healing.
Radiation therapy within 2 weeks prior to enrollment. Palliative radiation must have been completed at least 48 hours prior to enrollment. Stereotactic or partial brain irradiation must have completed at least 2 weeks prior to enrollment. Whole brain irradiation must have completed at least 4 weeks prior to enrollment.
Spinal cord compression unless the subject has good pain control attained through therapy, and there is complete recovery of neurological function for the 4 weeks prior to enrollment.
Gastrointestinal abnormalities, including inability to take oral medication; requirement for intravenous alimentation; prior surgical procedures affecting absorption including total gastric resection or lap band; active inflammatory gastrointestinal disease, chronic diarrhea, symptomatic diverticular disease; treatment for active peptic ulcer disease in the past 6 months; malabsorption syndromes.
Known prior or suspected severe hypersensitivity to lorlatinib or any component in the formulation; known prior therapy with lorlatinib.
Active and clinically significant bacterial, fungal, or viral infection including hepatitis B virus (HBV), hepatitis C virus (HCV), known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS) related illness.
Clinically significant cardiovascular disease (both arterial and venous) and non vascular cardiac conditions, (active or within 3 months prior to enrollment, which may include, but not are limited to:
Subject with predisposing characteristics for acute pancreatitis according to investigator judgment, including but not limited to uncontrolled hyperglycemia, current gallstone disease, in the last month prior to enrollment.
History of extensive, disseminated, bilateral or presence of Grade 3 or 4 interstitial fibrosis or interstitial lung disease including a history of pneumonitis, hypersensitivity pneumonitis, interstitial pneumonia, interstitial lung disease, obliterative bronchiolitis and pulmonary fibrosis.
Evidence of active malignancy (other than NSCLC, non melanoma skin cancer, or localized and presumed cured prostate cancer or any in situ cancer which does not currently require treatment) within the last 3 years prior to enrollment.
Concurrent use of any of the following food or drugs (consult the sponsor if in doubt whether a food or a drug falls into any of the above categories) within 12 days prior to the first dose of administration of lorlatinib:
Other severe acute or chronic medical or psychiatric condition, including recent (within the past year) or active suicidal ideation or behavior, or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator and/or the sponsor, would make the subject inappropriate for entry into this study.
Subject who are investigational site staff members directly involved in the conduct of the study and their family members, site staff members otherwise supervised by the investigator, or subjects who are Pfizer employees, including their family members, directly involved in the conduct of the study.
Participation in other studies involving investigational drug(s) within 2 weeks prior to study entry and/or during study participation.
Pregnant female participants; breastfeeding female participants; fertile male participants and female participants of childbearing potential who are unwilling or unable to use a highly effective method of contraception as outlined in this protocol for the duration of the study and for at least 97 days if male or 35 days if female, after the last dose of investigational product.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Gaoxin Hospital of The First Affilated Hospital of Anhui Medical University | Hefei | Anhui | 230088 | China | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 38879393 | Derived | Lu S, Zhou Q, Liu X, Du Y, Fan Y, Cheng Y, He S, Zhao H, Li H, Wu YL. Updated Efficacy and Safety of Lorlatinib in a Phase 2 Study in Chinese Patients With Previously Treated Advanced ALK-Positive Non-small Cell Lung Cancer. Clin Lung Cancer. 2024 Nov;25(7):e295-e303.e4. doi: 10.1016/j.cllc.2024.04.017. Epub 2024 Apr 30. | |
| 38344203 |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
Not provided
Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical\_trials/trial\_data\_and\_results/data\_requests.
Not provided
Not provided
Not provided
The study enrolled 109 participants, with 67 in Cohort 1 and 42 in Cohort 2.
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1 | Participants whose disease had progressed after crizotinib as the only anaplastic lymphoma kinase (ALK) inhibitor were enrolled in Cohort 1 to receive lorlatinib 100 mg orally once daily (QD) continuously until confirmed disease progression by Independent Central Radiology (ICR) (unless clinical benefit is still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, or the study is terminated by the sponsor, whichever comes first. Each cycle duration was 21 days. |
| FG001 | Cohort 2 | Participants whose disease had progressed after one ALK inhibitor treatment other than crizotinib, with or without prior crizotinib were enrolled in Cohort 2 to receive lorlatinib100 mg QD continuously until confirmed disease progression by ICR (unless clinical benefit is still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, or the study is terminated by the sponsor, whichever comes first. Each cycle duration was 21 days. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Not provided
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1 | Participants whose disease had progressed after crizotinib as the only ALK inhibitor were enrolled in Cohort 1 to receive lorlatinib 100 mg orally QD continuously until confirmed disease progression by ICR (unless clinical benefit is still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, or the study is terminated by the sponsor, whichever comes first. Each cycle duration was 21 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses |
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Participants With Objective Response (Cohort 1) | Objective response rate (ORR) was defined as the percentage of participants with a best overall confirmed response of complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST) version 1.1 relative to the total participants in the analysis population. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to less than (<) 10 millimeter (mm). PR was defined as a greater than equal to (>=) 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. Independent Central Radiology (ICR) was used for disease progression assessment. | The analysis population included all enrolled participants who received at least 1 dose of lorlatinib. | Posted | Number | 95% Confidence Interval | Percentage of participants | From Cycle 1 Day 1 to documented progression of disease by ICR (up to 67 weeks) |
|
From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks
The same event may appear as both non-SAE and a serious adverse event (SAE). However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another participant, or one participant may have experienced both a serious and non-serious event during the study. AE reporting, including suspected unexpected serious adverse reactions, was carried out in accordance with applicable local regulations.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1 | Participants whose disease had progressed after crizotinib as the only ALK inhibitor were enrolled in Cohort 1 to receive lorlatinib 100 mg orally QD continuously until confirmed disease progression by ICR (unless clinical benefit is still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, or the study is terminated by the sponsor, whichever comes first. Each cycle duration was 21 days. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v27.1 | Non-systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v27.1 | Non-systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Oct 11, 2019 | Aug 9, 2021 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Sep 11, 2020 | Aug 9, 2021 | SAP_001.pdf |
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D002289 | Carcinoma, Non-Small-Cell Lung |
| ID | Term |
|---|---|
| D002283 | Carcinoma, Bronchogenic |
| D001984 | Bronchial Neoplasms |
| D008175 | Lung Neoplasms |
| D012142 | Respiratory Tract Neoplasms |
Not provided
Not provided
| ID | Term |
|---|---|
| C000590786 | lorlatinib |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| From Cycle 1 Day 1 to documented progression of disease by ICR (up to 67 weeks) |
| Progression-Free Survival (PFS) Based on ICR Assessment | PFS was defined as the time from first dose to first documentation of objective disease progression (PD) or to death due to any cause, whichever came first. PD: at least a >=20 percent (%) increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, PD was defined as unequivocal progression of existing non-target lesions, or the appearance of >=1 new lesion. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. Analysis was performed using Kaplan Meier method. ICR was used for disease progression assessment. | From first dose (Cycle 1 Day 1) to documented PD by ICR, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure) |
| Progression-Free Survival Based on Investigator Assessment | PFS was defined as the time from first dose to first documentation of objective PD or to death due to any cause, whichever came first. PD: at least a >=20 % increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, PD was defined as unequivocal progression of existing non-target lesions, or the appearance of >=1 new lesion. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. Analysis was performed using Kaplan Meier method. Investigator assessment was used for disease progression assessment. | From first dose (Cycle 1 Day 1) to documented progression of disease by investigator, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure) |
| Overall Survival | Overall survival was defined as the time from first dose to the date of death due to any cause. Analysis was performed using Kaplan Meier method. | From first dose (Cycle 1 Day 1) to date of death due to any cause (up to 271 weeks of treatment exposure) |
| Percentage of Participants With Intracranial Objective Response (IC-OR) Based on ICR Assessment | IC-OR: percentage of participants with a best overall confirmed intracranial response of CR or PR according to RECIST version 1.1 relative to total participants in the analysis population but limited to intra cranial lesions only in participants with central nervous system metastases. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as a >= 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. 95% CI was based on Clopper-Pearson method. | From first dose (Cycle 1 Day 1) to documented PD by ICR (up to 271 weeks of treatment exposure) |
| Percentage of Participants With Intracranial Objective Response Based on Investigator Assessment | IC-OR: percentage of participants with a best overall confirmed intracranial response of CR or PR according to RECIST version 1.1 relative to total participants in the analysis population but limited to intra cranial lesions only in participants with central nervous system metastases. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as a >= 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. 95% CI was based on Clopper-Pearson method | From first dose (Cycle 1 Day 1) to documented progression of disease by investigator (up to 271 weeks of treatment exposure) |
| Duration of Response (DOR) Based on ICR Assessment | DOR: time from first documentation of CR or PR to first documentation of PD or death due to any cause, whichever occurred first. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes must have reduction in short axis to <10mm. PR:>=30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. PD:>=20 % increase in sum of longest dimensions of target lesions taking as a reference smallest sum of longest dimensions recorded since treatment started, or the appearance of one or more new lesions. In addition to relative increase of 20% sum must also demonstrate an absolute increase of at least 5 mm and for non-target lesions PD: unequivocal progression of existing non-target lesions or the appearance of >=1 new lesion. Participants without documentation of PD, or death at time of analysis were censored at date of last tumor assessment. Analysis was performed using Kaplan Meier method. | From first documentation of CR or PR to documented progression of disease by ICR, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure) |
| DOR Based on Investigator Assessment | DOR: time from first documentation of CR or PR to first documentation of PD or death due to any cause, whichever occurred first. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes must have reduction in short axis to <10mm. PR:>=30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. PD:>=20 % increase in sum of longest dimensions of target lesions taking as a reference smallest sum of longest dimensions recorded since treatment started, or the appearance of one or more new lesions. In addition to relative increase of 20% sum must also demonstrate an absolute increase of at least 5 mm and for non-target lesions PD: unequivocal progression of existing non-target lesions or the appearance of >=1 new lesion. Participants without documentation of PD, or death at time of analysis were censored at date of last tumor assessment. Analysis was performed using Kaplan Meier method. | From first documentation of CR or PR to documented PD by investigator, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure |
| Duration of Intracranial Response Based on ICR Assessment | Duration of intracranial response: time from first documentation of CR or PR considering only lesions having disease site=brain to first documentation of PD or death due to any cause, whichever occurred first, participants who had at least 1 intracranial lesion.CR: disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in <10mm.PR:>=30% decrease in the sum of the longest dimensions of target lesions taking reference the baseline sum longest dimension. PD:>=20% increase in sum of longest dimensions of target lesion, or appearance of one or more new lesion. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm and for non-target lesion PD: unequivocal progression of existing non-target lesion, or the appearance of >=1 new lesion. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. Kaplan Meier method was used. | From first documentation of CR or PR to documented progression of disease by ICR, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure) |
| Duration of Intracranial Response Based on Investigator Assessment | Duration of intracranial response: time from first documentation of CR or PR considering only lesions having disease site=brain to first documentation of PD or death due to any cause, whichever occurred first, participants who had at least 1 intracranial lesion.CR: disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in <10mm.PR:>=30% decrease in the sum of the longest dimensions of target lesions taking reference the baseline sum longest dimension. PD:>=20% increase in sum of longest dimensions of target lesion or appearance of one or more new lesion. In addition to relative increase of 20% sum must also demonstrate an absolute increase of at least 5mm and for non-target lesion PD: unequivocal progression of existing non-target lesion, or the appearance of >=1 new lesion. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. Kaplan Meier method was used. | From first documentation of CR or PR to documented progression of disease by investigator, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure) |
| Time to Tumor Response Based on ICR Assessment | Time to tumor response was defined as the time from first dose to first documentation of objective tumor response CR or PR. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | From first dose (Cycle 1 Day 1) to first documented CR or PR (up to 271 weeks of treatment exposure) |
| Time to Tumor Response Based on Investigator Assessment | Time to tumor response was defined as the time from first dose to first documentation of objective tumor response CR or PR. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | From first dose (Cycle 1 Day 1) to documented first CR or PR (up to 271 weeks of treatment exposure) |
| Number of Participants With Adverse Events (AEs) | AE:any untoward medical occurrence in a study participant administered a product or medical device;event did not necessarily have a causal relationship with treatment or usage.Serious AE:any untoward medical occurrence at any dose resulted in death;life-threatening;required inpatient or prolongation of existing hospitalization;persistent or significant disability/incapacity; congenital anomaly/birth defect or that was considered to be an important event.AEs were graded by the National Cancer Institute Common Terminology Criteria AE(NCICTCAE)v4.03 where,Grade(G)1:mild AE;G2:moderate;G3:severe;G4:life-threatening consequences,urgent intervention indicated;G5:death related to AE. Focus of AE summaries was on treatment-emergent AE(TEAE).AE was considered TEAE if the event occurred during the on-treatment period.On-treatment:time from first dose of study treatment through end of study follow-up(i.e.,up to 28 days after last dose of treatment. Participant with G3or4 and5 AEs were reported. | From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks |
| Number of Participants With Central Nervous System-Related Adverse Events | An AE was any untoward medical occurrence in a study participant administered a product or medical device; the event did not necessarily have a causal relationship with the treatment or usage. The central-nervous system-related AEs included AEs under the cluster terms of mood effects, cognitive effects, psychotic effects, and speech effects. | From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks |
| Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities | Laboratory tests included hematology, chemistry and lipids. Laboratory test results were graded according to NCI CTCAE version 4.03, where Grade 0: no AE, Grade 1 : mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Shifts from Grade <=2 at baseline to Grade 3 or 4 post-baseline were considered clinically significant. Only categories with non-zero values were reported in this outcome measure. | From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks |
| Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Vital signs evaluation included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse rate and weight. Blood pressure and pulse rate were recorded in sitting position after the participant had been sitting quietly for at least 5 minutes. The pre-specified criteria included: sitting SBP change >=40 millimeters of mercury (mmHg) increase, >=40 mmHg decrease; sitting DBP change >=20 mmHg increase, change >=20 mmHg decrease, or change >=60 mmHg increase; sitting pulse rate value <50 beats per minute (bpm), >120 bpm, change >=30 bpm increase, or change >=30 bpm decrease; weight 10% <= change <20% increase, change >=20% increase or change >=10% decrease. One participant can have more than one vital sign data meeting pre-specified criteria. | From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks |
| Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | The QT intervals were corrected for heart rate (QTc) using standard correction factors (ie, QTcF [Fridericia's], QTcB [Bazett's], and possibly a study-specified factor, as appropriate). The pre-specified criteria included: PR interval change >= 50% and baseline <200 msec, change >=25% and baseline >=200 msec; QRS interval change >=50% and baseline <100 msec, change >=25% and baseline >=100 msec; QTcB values <=450 msec, 450 < Value <= 480 msec, 480 < Value <= 500 msec, value >500 msec, change <=30 msec, 30 < Change <= 60 msec, change >60 msec; QTcF value <=450 msec, 450 < Value <= 480 msec, 480 < Value <= 500 msec, Value > 500 msec, change <=30 msec, 30 < Change <=60 msec and change >60 msec. . One participant can have more than one ECG data meeting pre-specified criteria. | From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks |
| Number of Participants With Left Ventricular Ejection Fraction (LVEF) Meeting Pre-specified Criteria | Echocardiogram or multigated acquisition scan were performed to monitor LVEF. Pre-specified criteria included shift from baseline normal to post-baseline below lower limit of normal (LLN) >=20-point decrease from baseline in LVEF% . | From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks |
| Cycle 1 Day 1 Maximum Plasma Concentration (Cmax) | The loratinib Cmax was estimated using non-compartmental analysis. | At pre-dose, 0.5, 1, 2, 3, 4, 6 ,8, 9 and 24 hours on Cycle 1 Day 1 |
| Cycle 1 Day 1 Time to Cmax (Tmax) | The loratinib Tmax was estimated using non-compartmental analysis. | At pre-dose, 0.5, 1, 2, 3, 4, 6 ,8, 9 and 24 hours on Cycle 1 Day 1 |
| Cycle 1 Day 1 Area Under the Plasma Concentration Versus Time Profile Within A Dose Interval (AUCtau) | The loratinib AUCtau was estimated using non-compartmental analysis. | At pre-dose, 0.5, 1, 2, 3, 4, 6 ,8, 9 and 24 hours on Cycle 1 Day 1 |
| Steady-State Cmax | The loratinib Cmax was estimated using non-compartmental analysis. Steady-state was reached on Cycle 1 Day 15. | At Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours on Day 15 of Cycle 1 |
| Steady-State Tmax | The loratinib Tmax was estimated using non-compartmental analysis. Steady-state was reached on Cycle 1 Day 15. | At Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours on Day 15 of Cycle 1 |
| Steady-State AUCtau | The loratinib AUCtau was estimated using non-compartmental analysis. Steady-state was reached on Cycle 1 Day 15. | At Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours on Day 15 of Cycle 1 |
| Apparent Clearance (CL/F) | The loratinib CL/F was estimated using non-compartmental analysis. Steady-state was reached on Cycle 1 Day 15. | At Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours on Day 15 of Cycle 1 |
| Observed Accumulation Ratio (Rac) | The loratinib Rac was estimated using non-compartmental analysis. Steady-state was reached on Cycle 1 Day 15. | At Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours on Day 15 of Cycle 1 |
| From first dose (Cycle 1 Day 1) to documented disease progression by ICR (up to 271 weeks of treatment exposure) |
| Beijing Cancer Hospital |
| Beijing |
| Beijing Municipality |
| 100142 |
| China |
| Fujian Province Oncology Hospital | Fuzhou | Fujian | 350014 | China |
| Harbin Medical University Cancer Hospital | Harbin | Heilongjiang | 150081 | China |
| Hunan Provincial Tumor Hospital/Division of Oncology | Changsha | Hunan | 410013 | China |
| The first hospital of jilin university | Changchun | Jilin | 130021 | China |
| Jilin Provincial Cancer Hospital | Changchun | Jilin | 130103 | China |
| Tangdu Hospital of Fourth Military Medical University | Xi’an | Shanxi | 710000 | China |
| Sichuan Province Cancer Hospital/Department of Pulmonary Tumor | Chengdu | Sichuan | 610041 | China |
| West China Hospital, Sichuan University, Cancer center | Chengdu | Sichuan | 610041 | China |
| The Second Affiliated Hospital of Zhejiang University College of Medicine | Hangzhou | Zhejiang | 310009 | China |
| Sir Run Run Shaw Hospital of College of Medicine of Zhejiang University, Center for Oncology | Hangzhou | Zhejiang | 310016 | China |
| Zhejiang Cancer Hospital | Hangzhou | Zhejiang | 310022 | China |
| Fifth Medical Center of PLA General Hospital | Beijing | 100071 | China |
| Beijing Chest Hospital, Capital Medical University | Beijing | 101149 | China |
| Guangdong Provincial People's Hospital | Guangzhou | 510000 | China |
| The First Affiliated Hospital Zhejiang University School of Medicine | Hangzhou | 310003 | China |
| General Hospital of Eastern Theater Command | Nanjing | China |
| Shanghai Chest Hospital | Shanghai | 200030 | China |
| Fudan University Shanghai Cancer Center | Shanghai | 200032 | China |
| Zhongshan Hospital, Fudan University | Shanghai | 200032 | China |
| Niu R, Zhang Y, Pang J, Zhou Q, Lei Y, Du Y. Effective treatment of advanced lung adenocarcinoma with paraneoplastic leukemoid reaction with Lorlatinib: a case report. Front Oncol. 2024 Jan 26;14:1341233. doi: 10.3389/fonc.2024.1341233. eCollection 2024. |
| Progressive Disease |
|
| Death |
|
| Adverse Event |
|
| Withdrawal by Subject |
|
| Participant was unwilling to come to site visit |
|
| No longer benefit from Lorlatinib |
|
| BG001 | Cohort 2 | Participants whose disease had progressed after one ALK inhibitor treatment other than crizotinib, with or without prior crizotinib were enrolled in Cohort 2 to receive lorlatinib 100 mg QD continuously until confirmed disease progression by ICR (unless clinical benefit is still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, or the study is terminated by the sponsor, whichever comes first. Each cycle duration was 21 days. |
| BG002 | Total | Total of all reporting groups |
| Years |
|
| Age, Customized | Count of Participants | Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| OG000 | Cohort 1 | Participants whose disease had progressed after crizotinib as the only ALK inhibitor were enrolled in Cohort 1 to receive lorlatinib 100 mg orally QD continuously until confirmed disease progression by ICR (unless clinical benefit is still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, or the study is terminated by the sponsor, whichever comes first. Each cycle duration was 21 days. |
|
|
|
| Other Pre-specified | Percentage of Participants With Objective Response (Cohort 1)-Final Analysis | ORR was defined as the percentage of participants with a best overall confirmed response of CR or PR according to RECIST version 1.1 relative to the total participants in the analysis population. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. ICR was used for disease progression assessment. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. | Posted | Number | 95% Confidence Interval | Percentage of participants | From first dose (Cycle 1 Day 1) to documented disease progression by ICR (up to 271 weeks of treatment exposure) |
|
|
|
| Secondary | Percentage of Participants With Objective Response (Cohort 2) | ORR was defined as the percentage of participants with a best overall confirmed response of CR or PR according to RECIST version 1.1 relative to the total participants in the analysis population. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. ICR was used for disease progression assessment. | The analysis population included all enrolled participants who received at least 1 dose of loratinib. | Posted | Number | 95% Confidence Interval | Percentage of participants | From Cycle 1 Day 1 to documented progression of disease by ICR (up to 67 weeks) |
|
|
|
| Secondary | Progression-Free Survival (PFS) Based on ICR Assessment | PFS was defined as the time from first dose to first documentation of objective disease progression (PD) or to death due to any cause, whichever came first. PD: at least a >=20 percent (%) increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, PD was defined as unequivocal progression of existing non-target lesions, or the appearance of >=1 new lesion. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. Analysis was performed using Kaplan Meier method. ICR was used for disease progression assessment. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. | Posted | Median | 95% Confidence Interval | Months | From first dose (Cycle 1 Day 1) to documented PD by ICR, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure) |
|
|
|
| Secondary | Progression-Free Survival Based on Investigator Assessment | PFS was defined as the time from first dose to first documentation of objective PD or to death due to any cause, whichever came first. PD: at least a >=20 % increase in the sum of the longest dimensions of the target lesions taking as a reference the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. For non-target lesions, PD was defined as unequivocal progression of existing non-target lesions, or the appearance of >=1 new lesion. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. Analysis was performed using Kaplan Meier method. Investigator assessment was used for disease progression assessment. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. | Posted | Median | 95% Confidence Interval | Months | From first dose (Cycle 1 Day 1) to documented progression of disease by investigator, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure) |
|
|
|
| Secondary | Overall Survival | Overall survival was defined as the time from first dose to the date of death due to any cause. Analysis was performed using Kaplan Meier method. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. | Posted | Median | 95% Confidence Interval | Months | From first dose (Cycle 1 Day 1) to date of death due to any cause (up to 271 weeks of treatment exposure) |
|
|
|
| Secondary | Percentage of Participants With Intracranial Objective Response (IC-OR) Based on ICR Assessment | IC-OR: percentage of participants with a best overall confirmed intracranial response of CR or PR according to RECIST version 1.1 relative to total participants in the analysis population but limited to intra cranial lesions only in participants with central nervous system metastases. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as a >= 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. 95% CI was based on Clopper-Pearson method. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. Here, 'Overall Number of Participants Analyzed' signifies participants for whom the brain lesions were chosen as RECIST target or non-target lesions at baseline and who were evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | Percentage of participants | From first dose (Cycle 1 Day 1) to documented PD by ICR (up to 271 weeks of treatment exposure) |
|
|
|
| Secondary | Percentage of Participants With Intracranial Objective Response Based on Investigator Assessment | IC-OR: percentage of participants with a best overall confirmed intracranial response of CR or PR according to RECIST version 1.1 relative to total participants in the analysis population but limited to intra cranial lesions only in participants with central nervous system metastases. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as a >= 30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. 95% CI was based on Clopper-Pearson method | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. Here, 'Overall Number of Participants Analyzed' signifies participants for whom the brain lesions were chosen as RECIST target or non-target lesions at baseline and who were evaluable for this outcome measure. | Posted | Number | 95% Confidence Interval | Percentage of participants | From first dose (Cycle 1 Day 1) to documented progression of disease by investigator (up to 271 weeks of treatment exposure) |
|
|
|
| Secondary | Duration of Response (DOR) Based on ICR Assessment | DOR: time from first documentation of CR or PR to first documentation of PD or death due to any cause, whichever occurred first. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes must have reduction in short axis to <10mm. PR:>=30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. PD:>=20 % increase in sum of longest dimensions of target lesions taking as a reference smallest sum of longest dimensions recorded since treatment started, or the appearance of one or more new lesions. In addition to relative increase of 20% sum must also demonstrate an absolute increase of at least 5 mm and for non-target lesions PD: unequivocal progression of existing non-target lesions or the appearance of >=1 new lesion. Participants without documentation of PD, or death at time of analysis were censored at date of last tumor assessment. Analysis was performed using Kaplan Meier method. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. Here "Overall Number of Participants Analyzed" signifies the number of participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From first documentation of CR or PR to documented progression of disease by ICR, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure) |
|
|
|
| Secondary | DOR Based on Investigator Assessment | DOR: time from first documentation of CR or PR to first documentation of PD or death due to any cause, whichever occurred first. CR: disappearance of all target lesions and non-target lesions. Any pathological lymph nodes must have reduction in short axis to <10mm. PR:>=30% decrease in sum of longest dimensions of target lesions taking as a reference baseline sum longest dimensions. PD:>=20 % increase in sum of longest dimensions of target lesions taking as a reference smallest sum of longest dimensions recorded since treatment started, or the appearance of one or more new lesions. In addition to relative increase of 20% sum must also demonstrate an absolute increase of at least 5 mm and for non-target lesions PD: unequivocal progression of existing non-target lesions or the appearance of >=1 new lesion. Participants without documentation of PD, or death at time of analysis were censored at date of last tumor assessment. Analysis was performed using Kaplan Meier method. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. Here "Overall Number of Participants Analyzed" signifies the number of participants evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From first documentation of CR or PR to documented PD by investigator, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure |
|
|
|
| Secondary | Duration of Intracranial Response Based on ICR Assessment | Duration of intracranial response: time from first documentation of CR or PR considering only lesions having disease site=brain to first documentation of PD or death due to any cause, whichever occurred first, participants who had at least 1 intracranial lesion.CR: disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in <10mm.PR:>=30% decrease in the sum of the longest dimensions of target lesions taking reference the baseline sum longest dimension. PD:>=20% increase in sum of longest dimensions of target lesion, or appearance of one or more new lesion. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm and for non-target lesion PD: unequivocal progression of existing non-target lesion, or the appearance of >=1 new lesion. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. Kaplan Meier method was used. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. Here, 'Overall Number of Participants Analyzed' signifies participants for whom the brain lesions were chosen as RECIST target or non-target lesions at baseline and who were evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From first documentation of CR or PR to documented progression of disease by ICR, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure) |
|
|
|
| Secondary | Duration of Intracranial Response Based on Investigator Assessment | Duration of intracranial response: time from first documentation of CR or PR considering only lesions having disease site=brain to first documentation of PD or death due to any cause, whichever occurred first, participants who had at least 1 intracranial lesion.CR: disappearance of all target and non-target lesions. Any pathological lymph nodes must have reduction in <10mm.PR:>=30% decrease in the sum of the longest dimensions of target lesions taking reference the baseline sum longest dimension. PD:>=20% increase in sum of longest dimensions of target lesion or appearance of one or more new lesion. In addition to relative increase of 20% sum must also demonstrate an absolute increase of at least 5mm and for non-target lesion PD: unequivocal progression of existing non-target lesion, or the appearance of >=1 new lesion. Participants without documentation of PD, or death at the time of analysis were censored at the date of the last tumor assessment. Kaplan Meier method was used. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. Here, 'Overall Number of Participants Analyzed' signifies participants for whom the brain lesions were chosen as RECIST target or non-target lesions at baseline and who were evaluable for this outcome measure. | Posted | Median | 95% Confidence Interval | Months | From first documentation of CR or PR to documented progression of disease by investigator, death due to any cause or date of censoring, whichever occurred first (up to 271 weeks of treatment exposure) |
|
|
|
| Secondary | Time to Tumor Response Based on ICR Assessment | Time to tumor response was defined as the time from first dose to first documentation of objective tumor response CR or PR. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. Here "Overall Number of Participants Analyzed" signifies the number of participants evaluable for this outcome measure. | Posted | Median | Full Range | Months | From first dose (Cycle 1 Day 1) to first documented CR or PR (up to 271 weeks of treatment exposure) |
|
|
|
| Secondary | Time to Tumor Response Based on Investigator Assessment | Time to tumor response was defined as the time from first dose to first documentation of objective tumor response CR or PR. CR was defined as the disappearance of all target lesions and non-target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. PR was defined as a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum longest dimensions. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. Here "Overall Number of Participants Analyzed" signifies the number of participants evaluable for this outcome measure. | Posted | Median | Full Range | Months | From first dose (Cycle 1 Day 1) to documented first CR or PR (up to 271 weeks of treatment exposure) |
|
|
|
| Secondary | Number of Participants With Adverse Events (AEs) | AE:any untoward medical occurrence in a study participant administered a product or medical device;event did not necessarily have a causal relationship with treatment or usage.Serious AE:any untoward medical occurrence at any dose resulted in death;life-threatening;required inpatient or prolongation of existing hospitalization;persistent or significant disability/incapacity; congenital anomaly/birth defect or that was considered to be an important event.AEs were graded by the National Cancer Institute Common Terminology Criteria AE(NCICTCAE)v4.03 where,Grade(G)1:mild AE;G2:moderate;G3:severe;G4:life-threatening consequences,urgent intervention indicated;G5:death related to AE. Focus of AE summaries was on treatment-emergent AE(TEAE).AE was considered TEAE if the event occurred during the on-treatment period.On-treatment:time from first dose of study treatment through end of study follow-up(i.e.,up to 28 days after last dose of treatment. Participant with G3or4 and5 AEs were reported. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. | Posted | Count of Participants | Participants | From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks |
|
|
|
| Secondary | Number of Participants With Central Nervous System-Related Adverse Events | An AE was any untoward medical occurrence in a study participant administered a product or medical device; the event did not necessarily have a causal relationship with the treatment or usage. The central-nervous system-related AEs included AEs under the cluster terms of mood effects, cognitive effects, psychotic effects, and speech effects. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. | Posted | Count of Participants | Participants | From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks |
|
|
|
| Secondary | Number of Participants With Clinically Significant Change From Baseline in Laboratory Abnormalities | Laboratory tests included hematology, chemistry and lipids. Laboratory test results were graded according to NCI CTCAE version 4.03, where Grade 0: no AE, Grade 1 : mild AE; Grade 2: moderate AE; Grade 3: severe AE; Grade 4: life-threatening consequence, urgent intervention indicated; Grade 5: death related to AE. Shifts from Grade <=2 at baseline to Grade 3 or 4 post-baseline were considered clinically significant. Only categories with non-zero values were reported in this outcome measure. | The safety analysis population included all enrolled participants who received at least 1 dose of Lorlatinib. Here, "Number Analyzed" signifies number of participants evaluable for each row. | Posted | Count of Participants | Participants | From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks |
|
|
|
| Secondary | Number of Participants With Vital Signs Data Meeting Pre-specified Criteria | Vital signs evaluation included diastolic blood pressure (DBP), systolic blood pressure (SBP), pulse rate and weight. Blood pressure and pulse rate were recorded in sitting position after the participant had been sitting quietly for at least 5 minutes. The pre-specified criteria included: sitting SBP change >=40 millimeters of mercury (mmHg) increase, >=40 mmHg decrease; sitting DBP change >=20 mmHg increase, change >=20 mmHg decrease, or change >=60 mmHg increase; sitting pulse rate value <50 beats per minute (bpm), >120 bpm, change >=30 bpm increase, or change >=30 bpm decrease; weight 10% <= change <20% increase, change >=20% increase or change >=10% decrease. One participant can have more than one vital sign data meeting pre-specified criteria. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. | Posted | Count of Participants | Participants | From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks |
|
|
|
| Secondary | Number of Participants With Electrocardiogram (ECG) Data Meeting Pre-specified Criteria | The QT intervals were corrected for heart rate (QTc) using standard correction factors (ie, QTcF [Fridericia's], QTcB [Bazett's], and possibly a study-specified factor, as appropriate). The pre-specified criteria included: PR interval change >= 50% and baseline <200 msec, change >=25% and baseline >=200 msec; QRS interval change >=50% and baseline <100 msec, change >=25% and baseline >=100 msec; QTcB values <=450 msec, 450 < Value <= 480 msec, 480 < Value <= 500 msec, value >500 msec, change <=30 msec, 30 < Change <= 60 msec, change >60 msec; QTcF value <=450 msec, 450 < Value <= 480 msec, 480 < Value <= 500 msec, Value > 500 msec, change <=30 msec, 30 < Change <=60 msec and change >60 msec. . One participant can have more than one ECG data meeting pre-specified criteria. | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib. | Posted | Count of Participants | Participants | From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks |
|
|
|
| Secondary | Number of Participants With Left Ventricular Ejection Fraction (LVEF) Meeting Pre-specified Criteria | Echocardiogram or multigated acquisition scan were performed to monitor LVEF. Pre-specified criteria included shift from baseline normal to post-baseline below lower limit of normal (LLN) >=20-point decrease from baseline in LVEF% . | The safety analysis population included all enrolled participants who received at least 1 dose of lorlatinib and who had at least 1 result of the LVEF value. Here "Overall Number of Participants Analyzed" signifies the number of participants evaluable for this outcome measure. | Posted | Count of Participants | Participants | From start of study treatment (Cycle 1 Day 1) up to 28 days after the last administration of the investigational product, up to approximately 275 weeks |
|
|
|
| Secondary | Cycle 1 Day 1 Maximum Plasma Concentration (Cmax) | The loratinib Cmax was estimated using non-compartmental analysis. | The analysis population included all enrolled participants who received at least 1 dose of loratinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram per milliliter (ng/mL) | At pre-dose, 0.5, 1, 2, 3, 4, 6 ,8, 9 and 24 hours on Cycle 1 Day 1 |
|
|
|
| Secondary | Cycle 1 Day 1 Time to Cmax (Tmax) | The loratinib Tmax was estimated using non-compartmental analysis. | The analysis population included all enrolled participants who received at least 1 dose of loratinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest. | Posted | Median | Full Range | hour | At pre-dose, 0.5, 1, 2, 3, 4, 6 ,8, 9 and 24 hours on Cycle 1 Day 1 |
|
|
|
| Secondary | Cycle 1 Day 1 Area Under the Plasma Concentration Versus Time Profile Within A Dose Interval (AUCtau) | The loratinib AUCtau was estimated using non-compartmental analysis. | The analysis population included all enrolled participants who received at least 1 dose of loratinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanogram*hour per milliliter (ng.hr/mL) | At pre-dose, 0.5, 1, 2, 3, 4, 6 ,8, 9 and 24 hours on Cycle 1 Day 1 |
|
|
|
| Secondary | Steady-State Cmax | The loratinib Cmax was estimated using non-compartmental analysis. Steady-state was reached on Cycle 1 Day 15. | The analysis population included all enrolled participants who received at least 1 dose of loratinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng/mL | At Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours on Day 15 of Cycle 1 |
|
|
|
| Secondary | Steady-State Tmax | The loratinib Tmax was estimated using non-compartmental analysis. Steady-state was reached on Cycle 1 Day 15. | The analysis population included all enrolled participants who received at least 1 dose of loratinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest. | Posted | Median | Full Range | hour | At Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours on Day 15 of Cycle 1 |
|
|
|
| Secondary | Steady-State AUCtau | The loratinib AUCtau was estimated using non-compartmental analysis. Steady-state was reached on Cycle 1 Day 15. | The analysis population included all enrolled participants who received at least 1 dose of loratinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | ng*hr/mL | At Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours on Day 15 of Cycle 1 |
|
|
|
| Secondary | Apparent Clearance (CL/F) | The loratinib CL/F was estimated using non-compartmental analysis. Steady-state was reached on Cycle 1 Day 15. | The analysis population included all enrolled participants who received at least 1 dose of loratinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | Liter per hour (L/hr) | At Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours on Day 15 of Cycle 1 |
|
|
|
| Secondary | Observed Accumulation Ratio (Rac) | The loratinib Rac was estimated using non-compartmental analysis. Steady-state was reached on Cycle 1 Day 15. | The analysis population included all enrolled participants who received at least 1 dose of loratinib and had sufficient information to estimate at least 1 of the pharmacokinetic parameters of interest. | Posted | Geometric Mean | Geometric Coefficient of Variation | Ratio | At Pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 9, and 24 hours on Day 15 of Cycle 1 |
|
|
|
| 28 |
| 67 |
| 23 |
| 67 |
| 67 |
| 67 |
| EG001 | Cohort 2 | Participants whose disease had progressed after one ALK inhibitor treatment other than crizotinib, with or without prior crizotinib were enrolled in Cohort 2 to receive lorlatinib 100 mg QD continuously until confirmed disease progression by ICR (unless clinical benefit is still achievable), participant refusal, participant lost to follow-up, unacceptable toxicity, or the study is terminated by the sponsor, whichever comes first. Each cycle duration was 21 days. | 26 | 42 | 16 | 42 | 42 | 42 |
| Pericarditis constrictive | Cardiac disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Death | General disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Disease progression | General disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Sudden death | General disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Cholecystitis | Hepatobiliary disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Cholelithiasis | Hepatobiliary disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Drug-induced liver injury | Hepatobiliary disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hepatic lesion | Hepatobiliary disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Liver injury | Hepatobiliary disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| COVID-19 pneumonia | Infections and infestations | MedDRA v27.1 | Non-systematic Assessment |
|
| Diarrhoea infectious | Infections and infestations | MedDRA v27.1 | Non-systematic Assessment |
|
| Febrile infection | Infections and infestations | MedDRA v27.1 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA v27.1 | Non-systematic Assessment |
|
| Post procedural infection | Infections and infestations | MedDRA v27.1 | Non-systematic Assessment |
|
| Soft tissue infection | Infections and infestations | MedDRA v27.1 | Non-systematic Assessment |
|
| Ulna fracture | Injury, poisoning and procedural complications | MedDRA v27.1 | Non-systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Intervertebral disc protrusion | Musculoskeletal and connective tissue disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Lung neoplasm malignant | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v27.1 | Non-systematic Assessment |
|
| Neoplasm progression | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA v27.1 | Non-systematic Assessment |
|
| Carpal tunnel syndrome | Nervous system disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Cerebral haemorrhage | Nervous system disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Cerebral infarction | Nervous system disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Lacunar infarction | Nervous system disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Mental disorder | Psychiatric disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Acute kidney injury | Renal and urinary disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Bronchial haemorrhage | Respiratory, thoracic and mediastinal disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Respiratory failure | Respiratory, thoracic and mediastinal disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Embolism | Vascular disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Atrioventricular block first degree | Cardiac disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Sinus bradycardia | Cardiac disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Sinus tachycardia | Cardiac disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Ventricular extrasystoles | Cardiac disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Oedema peripheral | General disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Pain | General disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Peripheral swelling | General disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hepatic function abnormal | Hepatobiliary disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hepatic steatosis | Hepatobiliary disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Albumin urine present | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Amylase increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood alkaline phosphatase increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood cholesterol increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood creatinine increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood glucose increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood lactate dehydrogenase increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood triglycerides increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood urea increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Electrocardiogram QT prolonged | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Gamma-glutamyltransferase increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Haemoglobin decreased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| High density lipoprotein increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Lipase increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Low density lipoprotein increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Platelet count decreased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Weight increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Hypercholesterolaemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hyperlipidaemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hypertriglyceridaemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hyperuricaemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hypokalaemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hypoaesthesia | Nervous system disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Haematuria | Renal and urinary disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Proteinuria | Renal and urinary disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hypertension | Vascular disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Arrhythmia | Cardiac disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Left ventricular dysfunction | Cardiac disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Pericardial effusion | Cardiac disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Supraventricular extrasystoles | Cardiac disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Tinnitus | Ear and labyrinth disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Chest discomfort | General disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| COVID-19 | Infections and infestations | MedDRA v27.1 | Non-systematic Assessment |
|
| Pneumonia | Infections and infestations | MedDRA v27.1 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA v27.1 | Non-systematic Assessment |
|
| Suspected COVID-19 | Infections and infestations | MedDRA v27.1 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood albumin decreased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood bilirubin increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood creatine phosphokinase increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood phosphorus decreased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood pressure increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Blood uric acid increased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| SARS-CoV-2 test positive | Investigations | MedDRA v27.1 | Non-systematic Assessment |
|
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hypomagnesaemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hyponatraemia | Metabolism and nutrition disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Pain in extremity | Musculoskeletal and connective tissue disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Dizziness | Nervous system disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Paraesthesia | Nervous system disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Pleural effusion | Respiratory, thoracic and mediastinal disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Productive cough | Respiratory, thoracic and mediastinal disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Pulmonary hypertension | Respiratory, thoracic and mediastinal disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Hyperhidrosis | Skin and subcutaneous tissue disorders | MedDRA v27.1 | Non-systematic Assessment |
|
| Pyrexia | General disorders | MedDRA v27.1 | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclosure previously undisclosed confidential information other than study results.
| D013899 |
| Thoracic Neoplasms |
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D008171 | Lung Diseases |
| D012140 | Respiratory Tract Diseases |
| All-causality serious AEs |
|
| Treatment-related serious AEs |
|
| All-causalities maximum Grade 3 or 4 AEs |
|
| Treatment-related Grade 3 or 4 AEs |
|
| All-causality Grade 5 AEs |
|
| Treatment-related Grade 5 AEs |
|
| Speech Effects |
|
| Psychotic Effects |
|
| Anemia:Grade 1 to Grade 3 or 4 |
|
|
| Anemia:Grade 2 to Grade 3 or 4 |
|
|
| Lymphocyte count decreased Grade 0 to Grade 3 or 4 |
|
|
| Lymphocyte count decreased:Grade 1 to Grade 3 or 4 |
|
|
| Platelet count decreased: Grade 0 to Grade 3 or 4 |
|
|
| Alanine aminotransferase increased: Grade 0 to Grade 3 or 4 |
|
|
| Alanine aminotransferase increased:Grade 1 to Grade 3 or 4 |
|
|
| Alkaline phosphatase increased: Grade 0 to Grade 3 or 4 |
|
|
| Aspartate aminotransferase increased: Grade 0 to Grade 3 or 4 |
|
|
| Aspartate aminotransferase increased:Grade 1 to Grade 3 or 4 |
|
|
| Blood bilirubin increased: Grade 0 to Grade 3 or 4 |
|
|
| Blood bilirubin increased:Grade 1 to Grade 3 or 4 |
|
|
| CPK increased: Grade 0 to Grade 3 or 4 |
|
|
| CPK increased:Grade 2 to Grade 3 or 4 |
|
|
| Creatinine increased: Grade 0 to Grade 3 or 4 |
|
|
| GGT increased: Grade 0 to Grade 3 or 4 |
|
|
| GGT increased:Grade 1 to Grade 3 or 4 |
|
|
| Hypercalcemia: Grade 0 to Grade 3 or 4 |
|
|
| Hyperglycemia: Grade 0 to Grade 3 or 4 |
|
|
| Hyperglycemia:Grade 1 to Grade 3 or 4 |
|
|
| Hypermagnesemia: Grade 0 to Grade 3 or 4 |
|
|
| Hypocalcemia: Grade 0 to Grade 3 or 4 |
|
|
| Hypokalemia: Grade 0 to Grade 3 or 4 |
|
|
| Hypokalemia:Grade 2 to Grade 3 or 4 |
|
|
| Hyponatremia: Grade 0 to Grade 3 or 4 |
|
|
| Hyponatremia:Grade 1 to Grade 3 or 4 |
|
|
| Hypophosphatemia: Grade 0 to Grade 3 or 4 |
|
|
| Hypophosphatemia:Grade 1 to Grade 3 or 4 |
|
|
| Lipase increased: Grade 0 to Grade 3 or 4 |
|
|
| Lipase increased:Grade 1 to Grade 3 or 4 |
|
|
| Serum amylase increased: Grade 0 to Grade 3 or 4 |
|
|
| Cholesterol high: Grade 0 to Grade 3 or 4 |
|
|
| Cholesterol high:Grade 1 to Grade 3 or 4 |
|
|
| Cholesterol high:Grade 2 to Grade 3 or 4 |
|
|
| Hypertriglyceridemia: Grade 0 to Grade 3 or 4 |
|
|
| Hypertriglyceridemia:Grade 1 to Grade 3 or 4 |
|
|
| Hypertriglyceridemia:Grade 2 to Grade 3 or 4 |
|
|
| Sitting DBP change >=20 mmHg increase |
|
| Sitting DBP change >=20 mmHg decrease |
|
| Sitting DBP change >=60 mmHg increase |
|
| Sitting pulse rate value <50 bpm |
|
| Sitting pulse rate value >120 bpm |
|
| Sitting pulse rate change >=30 mmHg increase |
|
| Sitting pulse rate change >=30 mmHg decrease |
|
| weight 10% <= change <20% kg increase |
|
| Weight change >=20% kg increase |
|
| Weight change >=10% kg decrease |
|
| QRS interval change >=50% and baseline<100 msec |
|
| QRS interval change >=25% and baseline >=100 msec |
|
| QTcB value <=450 msec |
|
| QTcB 450 < Value <= 480 msec |
|
| QTcB 480 < Value <= 500 msec |
|
| QTcB value >500 msec |
|
| QTcB change <=30 msec |
|
| QTcB 30 < Change <= 60 msec |
|
| QTcB change >60 msec |
|
| QTcF value <=450 msec |
|
| QTcF 450 < Value <= 480 msec |
|
| QTcF 480 < Value <= 500 msec |
|
| QTcF value >500 msec |
|
| QTcF change <=30 msec |
|
| QTcF 30 < Change <= 60 msec |
|
| QTcF change >60 msec |
|