An Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Phase 2, Open-label Study of Encorafenib + Binimetinib in Patients With BRAFV600-mutant Non-small Cell Lung Cancer

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT03915951
• Other study ID #: ARRAY-818-202
• Secondary ID: C42210082019-000
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: June 4, 2019
• Est. completion date: October 1, 2024

Study information

• Verified date: April 2024
• Source: Pfizer
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is an open-label, multicenter, non-randomized, Phase 2 study to determine the safety, tolerability and efficacy of encorafenib given in combination with binimetinib in patients with BRAFV600E-mutant metastatic non-small cell lung cancer (NSCLC). Patients who are either treatment-naïve, OR who have received 1) first-line treatment with standard platinum-based chemotherapy, OR 2) first-line treatment with an anti-programmed cell death protein 1 (PD-1)/programmed cell death protein ligand 1 (PD-L1) inhibitor given alone or in combination with platinum-based chemotherapy will be enrolled.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 98
• Est. completion date: October 1, 2024
• Est. primary completion date: September 22, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Key Inclusion Criteria:

• Histologically confirmed diagnosis of non-small cell lung cancer (NSCLC) that is currently Stage IV.
• Presence of a BRAFV600E mutation in lung cancer tissue as determined by a local laboratory assay or the presence of other BRAFV600 mutations other than V600E (i.e. K or D) will be considered
• Patients who are either treatment-naïve (e.g., no prior systemic therapy for advanced/metastatic disease), OR who have received 1) first-line platinum-based chemotherapy OR 2) first-line treatment with an anti-programmed cell death protein 1 (PD-1)/ programmed cell death protein ligand 1(PD-L1) inhibitor given alone or in combination with platinum-based chemotherapy.
• Presence of measurable disease based on Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1).
• Eastern Cooperation Oncology Group (ECOG) performance status of 0 or 1.
• Adequate bone marrow function characterized by the following at screening:
• absolute neutrophil count (ANC) = 1.5 × 10?/L;
• Platelets = 100 × 10?/L;
• Hemoglobin = 8.5 g/dL (with or without blood transfusions).
• Adequate hepatic and renal function characterized by the following at screening:
• Total bilirubin = 1.5 × upper limit of normal (ULN)
• alanine aminotransferase (ALT) and aspartate aminotransferase (AST) = 2.5 × ULN, or = 5 × ULN in presence of liver metastases; Serum creatinine = 1.5 × ULN; or calculated creatinine clearance = 50 mL/min by Cockcroft-Gault formula; or estimated glomerular filtration rate > 50 mL/min/1.73m².

Key Exclusion Criteria:

• Patients who have documentation of any of the following:
• epidermal growth factor receptor (EGFR) mutation
• anaplastic lymphoma kinase (ALK) fusion oncogene or
• ROS1 rearrangement
• Patients who have received more than 1 prior line of systemic therapy in the advanced/metastatic setting.
• Previous treatment with any BRAF inhibitor (e.g., dabrafenib, vemurafenib, XL281/BMS-908662, etc.), or any mitogen-activated protein kinase (MEK) inhibitor (e.g., trametinib, cobimetinib, selumetinib, RDEA119, etc.) prior to screening and enrollment.
• Impaired cardiovascular function or clinically significant cardiovascular diseases
• History of thromboembolic or cerebrovascular events = 12 weeks prior to the first dose of study treatment. Examples include transient ischemic attacks, cerebrovascular accidents, hemodynamically significant (i.e. massive or sub-massive) deep vein thrombosis or pulmonary emboli.
• History or current evidence of retinal vein occlusion (RVO) or current risk factors for RVO (e.g., uncontrolled glaucoma or ocular hypertension, history of hyperviscosity or hypercoagulability syndromes); history of retinal degenerative disease.
• Concurrent neuromuscular disorder that is associated with the potential of elevated creatine (phospho)kinase (CK) (e.g., inflammatory myopathies, muscular dystrophy, amyotrophic lateral sclerosis, spinal muscular atrophy).
• Patients with symptomatic brain metastasis, leptomeningeal disease or other active central nervous system (CNS) metastases are not eligible.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

Drug:
• encorafenib
self-administered orally
• binimetinib
self-administered orally

Locations

Country	Name	City	State
Italy	UO Dermatologia Centro Tumori Cutanei (CTC)- Azienda Ospedaliero	Bologna
Italy	UO di Oftalmologia- Azienda Ospedaliero Universitaria Di Bologna	Bologna
Italy	UO Medicina Borghi- Azienda Ospedaliero Universitaria Di Bologna	Bologna
Italy	UO Radiologia Golfieri- Azienda Ospedaliero Universitaria Di Bologna - Policlinico S Orsola Malpighi	Bologna
Italy	UOC di Anatomia Patologica- Azienda Ospedaliero Universitaria Di Bo logna	Bologna
Italy	Departimento Oncologia Medica	Milan	Lombardia
Italy	IRCCS Ospedale San Raffaele	Milan
Italy	Unita Operativa di Oculistica: UO Oncologia Oculare e Immunopatologia oculare	Milan	Lombardia
Italy	Unita Operativa Radiologia	Milan	Lombardia
Italy	UO Anatomia e lstologia Patologica	Milan	Lombardia
Italy	UO Dermatologia e Cosmetologia	Milan	Lombardia
Italy	UO Medicina Nucleare	Milan	Lombardia
Italy	Clinica Oculistica II, 2° Policlinico Federico II	Napli
Italy	S. C. Farmacia	Napoli
Italy	S.S.D. Oncologia Polmonare	Orbassano	Torino
Italy	SCDO Cardiologia	Orbassano	Torino
Italy	SCDU Anatomia Patologica	Orbassano	Torino
Italy	SCDU Oftalmologia	Orbassano	Torino
Italy	SCDU Radiodiagnostica e S.S. Medicina Nucleare	Orbassano	Torino
Italy	Dermatologia Azienda Ospedaliero Universitaria Città della Salute e della Scienza di Torino	Torino	TO
Korea, Republic of	Samsung Medical Center	Seoul
Korea, Republic of	Samsung Medical Center - PPDS	Seoul
Netherlands	Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam	Noord-holland
Netherlands	Het Nederlands Kanker Instituut Antoni Van Leeuwenhoek Ziekenhuis	Amsterdam
Netherlands	OLVG, locatie Oost; Ophthalmology department	Amsterdam
Netherlands	Ophthalmology department	Groningen
Netherlands	University Medical Center Groningen	Groningen
Spain	Hospital Clinic de Barcelona	Badalona
Spain	CETIR Centro Medico Teknon	Barcelona
Spain	Hospital del Mar	Barcelona
Spain	Hospital Quiron Salud Barcelona	Barcelona
Spain	Hospital Universitario Vall d'Hebron	Barcelona
Spain	Universitario Vall d'Hebron	Barcelona
Spain	Grupo Cardiologico Corpal (Hospital de la Cruz Roja)	Cordoba
Spain	Hospital Universitario Reina Sofia	Cordoba
Spain	Cetir	Esplugues de Llobregat
Spain	lnstitut Catala d'Oncologia_L'Hospitalet	L'Hospitalet
Spain	Hospital Universitario 12 de Octubre	Madrid
Spain	Hospital Universitario Ramon y Cajal	Madrid
Spain	Hospital Universitario Puerta de Hierro - Majadahonda	Majadahonda	Madrid
Spain	Centro Hospitalario Integral Privado (CHIP)	Malaga
Spain	Hospital Regional Universitario de Malaga - Hospital General	Malaga	Málaga
Spain	CERCO	Sevilla
Spain	Hospital Universitario Virgen Del Rocio	Sevilla
Spain	Hospital Universitario Virgen Macarena	Sevilla
United States	Florida Cancer Specialist	Altamonte Springs	Florida
United States	Emory University Hospital	Atlanta	Georgia
United States	Winship Cancer Institute @ Emory Saint Joseph's Hospital	Atlanta	Georgia
United States	Winship Cancer Institute @ Emory University Hospital Midtown	Atlanta	Georgia
United States	Winship Cancer Institute, Emory University	Atlanta	Georgia
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	Johns Hopkins Sidney Kimmel Comprehensive Cancer Center	Baltimore	Maryland
United States	The Johns Hopkins Wilmer Eye Institute	Baltimore	Maryland
United States	Memorial Sloan Kettering Cancer Center Basking Ridge	Basking Ridge	New Jersey
United States	Florida Cancer Specialists	Bonita Springs	Florida
United States	Beth Israel Deaconess Medical Center	Boston	Massachusetts
United States	Beth Israel Deaconess Medical Center - 330 Brookline Ave	Boston	Massachusetts
United States	Beth Israel Deaconess Medical Center/East	Boston	Massachusetts
United States	Brigham and Women's Hospital	Boston	Massachusetts
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Ophthalmic Consultants of Boston (OCB)	Boston	Massachusetts
United States	Ophthalmic Consultants of Boston Inc	Boston	Massachusetts
United States	Florida Cancer Specialist	Brandon	Florida
United States	Florida Cancer Specialists	Cape Coral	Florida
United States	Tennessee Oncology, PLLC	Chattanooga	Tennessee
United States	Providence Cancer Institute Clackamas Clinic	Clackamas	Oregon
United States	Florida Cancer Specialist	Clearwater	Florida
United States	Tennessee Oncology, PLLC	Cleveland	Tennessee
United States	Martha Morehouse Medical Plaza	Columbus	Ohio
United States	Ohio State CarePoint East	Columbus	Ohio
United States	Ohio State Eye and Ear Institute	Columbus	Ohio
United States	Stefanie Spielman Comprehensive Breast Cancer	Columbus	Ohio
United States	The Ohio State University East Hospital	Columbus	Ohio
United States	The Ohio State University Hospital	Columbus	Ohio
United States	The Ohio State University James Cancer Hospital	Columbus	Ohio
United States	The Ohio State University Medical Center - Thoracic Oncology Clinic	Columbus	Ohio
United States	Siteman Cancer Center - West County	Creve Coeur	Missouri
United States	Tennessee Oncology, PLLC	Dickson	Tennessee
United States	Duke Cancer Center	Durham	North Carolina
United States	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania
United States	Florida Cancer Specialists	Fleming Island	Florida
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Tennessee Oncology, PLLC	Franklin	Tennessee
United States	Ohio State CarePoint Gahanna	Gahanna	Ohio
United States	Florida Cancer Specialist	Gainesville	Florida
United States	Tennessee Oncology, PLLC	Gallatin	Tennessee
United States	UPMC Hillman Cancer Center - Arnold Palmer - Mt View	Greensburg	Pennsylvania
United States	Hackensack University Medical Center	Hackensack	New Jersey
United States	Tennessee Oncology, PLLC	Hendersonville	Tennessee
United States	Tennessee Oncology, PLLC	Hermitage	Tennessee
United States	Houston Eye Associates - Gramercy Location	Houston	Texas
United States	Millennium Research & Clinical Development	Houston	Texas
United States	The University of Texas MD Anderson Cancer Center	Houston	Texas
United States	MidAmerica Division, Inc. c/o Centerpoint Medical Center	Independence	Missouri
United States	Winship Cancer Institute @ Emory Johns Creek Hospital	Johns Creek	Georgia
United States	MidAmerica Division, Inc., c/o Research Medical Center	Kansas City	Missouri
United States	Florida Cancer Specialists	Largo	Florida
United States	Tennessee Oncology, PLLC	Lebanon	Tennessee
United States	Florida Cancer Specialist	Lecanto	Florida
United States	Ohio State Outpatient Care Lewis Center	Lewis Center	Ohio
United States	UPMC Hillman Cancer Center Monroeville	Monroeville	Pennsylvania
United States	Tennessee Oncology, PLLC	Murfreesboro	Tennessee
United States	Florida Cancer Specialists	Naples	Florida
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Tennessee Oncology, PLLC	Nashville	Tennessee
United States	Memorial Sloan Kettering Cancer Center	New York	New York
United States	Memorial Sloan Kettering Cancer Center David H Koch Center for Cancer Care	New York	New York
United States	Weill Cornell Eye Associates	New York	New York
United States	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York
United States	Weill Cornell Medical College - New York Presbyterian Hospital	New York	New York
United States	Providence Cancer Institute Newberg Clinic	Newberg	Oregon
United States	Dana-Farber Cancer Institute - Chestnut Hill	Newton	Massachusetts
United States	Florida Cancer Specialist	Ocala	Florida
United States	Florida Cancer Specialist	Orange City	Florida
United States	Florida Cancer Specialist	Orlando	Florida
United States	MidAmerica Division, Inc. c/o Menorah Medical Center	Overland Park	Kansas
United States	Metropolitan Eye Care	Paramus	New Jersey
United States	UPMC Eye Center, Eye and Ear Institute	Pittsburgh	Pennsylvania
United States	UPMC Hillman Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC Hillman Cancer Center - Passavant (HOA)	Pittsburgh	Pennsylvania
United States	UPMC Hillman Cancer Center - Passavant (OHA)	Pittsburgh	Pennsylvania
United States	UPMC Hillman Cancer Center - Upper St. Clair	Pittsburgh	Pennsylvania
United States	Florida Cancer Specialists	Port Charlotte	Florida
United States	Providence Cancer Institute, Franz Clinic	Portland	Oregon
United States	Providence Oncology and Hematology Care Clinic - Westside	Portland	Oregon
United States	Barnes-Jewish Hospital	Saint Louis	Missouri
United States	Siteman Cancer Center - South County	Saint Louis	Missouri
United States	Washington University School of Medicine	Saint Louis	Missouri
United States	Siteman Cancer Center - St Peters	Saint Peters	Missouri
United States	Florida Cancer Specialist	Saint Petersburg	Florida
United States	UCLA Hematology/Oncology	Santa Monica	California
United States	UCLA Stein Eye Center Santa Monica (OPH)	Santa Monica	California
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Florida Cancer Specialists	Sarasota	Florida
United States	Eye associates Northwest	Seattle	Washington
United States	Seattle Cancer Care Alliance	Seattle	Washington
United States	Tennessee Oncology, PLLC	Shelbyville	Tennessee
United States	Tennessee Oncology, PLLC	Smyrna	Tennessee
United States	Florida Cancer Specialists	Spring Hill	Florida
United States	Florida Cancer Specialists PAN - SCRI - PPDS	Tallahassee	Florida
United States	Florida Cancer Specialist	Tampa	Florida
United States	Florida Cancer Specialist	Tavares	Florida
United States	Florida Cancer Specialist	The Villages	Florida
United States	Florida Cancer Specialist	Trinity	Florida
United States	Florida Cancer Specialists	Venice	Florida
United States	Florida Cancer Specialists	Venice	Florida
United States	The Ohio State University East Hospital Ohio State Outpatient Care New Albany	Westerville	Ohio
United States	Florida Cancer Specialists	Winter Park	Florida
United States	Weaver Eye Associates	York	Pennsylvania
United States	WellSpan Oncology Research	York	Pennsylvania
United States	Yuma Regional Medical Center	Yuma	Arizona
United States	Yuma Regional Medical Center Cancer Center	Yuma	Arizona
United States	Yuma Regional Medical Center Ophthalmology	Yuma	Arizona

Sponsors (1)

Lead Sponsor	Collaborator
Pfizer

Countries where clinical trial is conducted

United States,  Italy,  Korea, Republic of,  Netherlands,  Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Percentage of Participants With Confirmed Objective Response (OR) as Determined by Independent Radiology Review (IRR)	Objective Response Rate (ORR) was defined as the percentage of participants who had achieved a confirmed best overall response (Complete Response [CR] or Partial Response [PR]) per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. CR was defined by the disappearance of all non-lymph node target lesions (where all target lesions were recorded with a length of 0 mm, and any pathological lymph nodes [recorded as target lesion] must have reduction in short axis to <10 mm) and complete disappearance of all non-target lesions (where all non-target lesions were marked "Absent", and all lymph nodes must be non-pathological in size [<10 mm in short axis]). PR was defined by a 30% or more decrease in sum of diameters (SOD) of target lesions, taking as reference the baseline SOD. ORR was calculated with the exact 2-sided Clopper-Pearson 95% CI.	From date of the first dose of study intervention until documented progressive disease (PD) or start of new anticancer therapy (up to 36 months)
Secondary	Percentage of Participants With Confirmed Objective Response (OR) by Investigator Assessment	ORR was defined as the percentage of participants who had achieved a confirmed best overall response (CR or PR) per RECIST version 1.1. Both CR and PR must be confirmed by repeat assessments performed no less than 4 weeks after the criteria for response were first met. CR was defined by the disappearance of all non-lymph node target lesions (where all target lesions were recorded with a length of 0 mm, and any pathological lymph nodes [recorded as target lesion] must have reduction in short axis to <10 mm) and the complete disappearance of all non-target lesions (where all non-target lesions were marked "Absent", and all lymph nodes must be non-pathological in size [<10 mm in short axis]). PR was defined by a 30% or more decrease in SOD of target lesions, taking as reference the baseline SOD. ORR according to derived investigator assessment was calculated with the exact 2-sided Clopper-Pearson 95% CI.	From date of the first dose of study intervention until documented PD or start of new anticancer therapy (up to 36 months)
Secondary	Duration of Response (DoR) by IRR and Investigator Assessments	DoR, based on IRR and Investigator assessments was defined as the time from the date of the first documented confirmed response (CR or PR) (by IRR and by Investigator, respectively) to the earliest date of disease progression, as determined by Investigator review of radiographic disease assessments and IRR per RECIST version 1.1, or death due to any cause. If a participant with a CR or PR had neither progressed nor died at the time of the analysis cutoff or at the start of any new anticancer therapy, the participant was censored at the date of last adequate tumor assessment. CR was defined by the disappearance of all non-lymph node target lesions and complete disappearance of all non-target lesions. PR was defined by a 30% or more decrease in SOD of target lesions, taking as reference the baseline SOD. DoR was calculated for participants who had achieved a confirmed overall response (CR or PR). The estimate of the DoR survival function was constructed using the Kaplan-Meier method.	From the date of the first confirmed documented response (CR or PR) to the earliest date of disease progression or death due to any cause (up to 36 months)
Secondary	Disease Control Rate (DCR) by IRR and Investigator Assessments	DCR was defined as the percentage of participants who had achieved a confirmed overall response of CR, PR or stable disease (SD), as determined by Investigator review of radiographic disease assessments and IRR per RECIST version 1.1 after 24 weeks (=168 days) from the date of first dose of study intervention. CR was defined by the disappearance of all non-lymph node target lesions and complete disappearance of all non-target lesions. PR was defined by a 30% or more decrease in SOD of target lesions, taking as reference the baseline SOD. SD was assigned when neither sufficient shrinkage to qualify for CR or PR, nor sufficient increase to qualify for PD was observed, taking as reference the nadir. DCR was calculated along with the exact 2-sided Clopper-Pearson 95% CI.	After 24 Weeks (=168 days) from the date of first dose of study intervention
Secondary	Progression-free Survival (PFS) by IRR and Investigator Assessments	PFS was defined as the time from the date of first dose of study intervention to the earliest date of disease progression, as determined by IRR and Investigator review of radiographic disease assessments per RECIST version 1.1, or death due to any cause, whichever occurred first. PD was defined by a 20% or more increase in the SOD of target lesions relative to nadir (smallest SOD considering baseline and all assessments prior to the time point under evaluation), with a minimum absolute increase of 5 mm relative to nadir; PD was assigned if any non-target lesion was marked "unequivocal progression". If a participant had not had a PFS event at the time of the analysis cutoff or at the start of any new anticancer therapy, PFS was censored at the date of last adequate tumor assessment. PFS (months) = [(date of event or censoring - date of first dose) +1]/30.4375. The survival distribution function for PFS was estimated using the Kaplan-Meier method.	From the date of first dose of study drug to the earliest date of disease progression, or death due to any cause (up to 36 months)
Secondary	Time to Response (TTR) by IRR and Investigator Assessments	TTR based on IRR and Investigator assessments was defined, for participants with an objective response, as the time, in months, from the date of first dose to the first documentation of objective response (CR or PR) which was subsequently confirmed (by IRR and by Investigator, respectively). TTR was calculated for the subgroup of participants with a confirmed objective tumor response.	From the date of first dose to the first documentation of confirmed objective response (CR or PR) (up to 36 months)
Secondary	Kaplan-Meier Estimates of Overall Survival (OS)	OS was defined as the time from the date of first dose of study intervention to the date of death due to any cause. If a death had not been observed by the date of the analysis cutoff, OS was censored at the date of last contact. The survival distribution function for OS was estimated using the Kaplan-Meier method.	The time from the date of first dose of study intervention to the date of death due to any cause (up to 36 months)
Secondary	Number of Participants With Treatment-Emergent Adverse Events (TEAEs)	TEAE was a treatment-emergent adverse event that occurred during the on-treatment period. The on-treatment period was defined as the time from the first dose date of study intervention to the last dose of study drug administration date (when both drugs were permanently discontinued) +30 days or the earliest date of subsequent anti-cancer drug therapy minus 1 day, whichever occurred first. Relatedness to study intervention was determined by the investigator. The investigator made an assessment of intensity for each AE reported during the study according to the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.03: Grade 3 events = severe AEs; Grade 4 events = life-threatening consequences, urgent intervention indicated; Grade 5 events = death related to AEs.	From the time the participant provided informed consent, through and including a minimum of 30 calendar days, after the last administration of the study intervention, and the safety follow-up visit (30 days [±7 days] after the EOT visit) (up to 36 months)
Secondary	Number of Participants With Shifts From Grade =2 at Baseline to Grade 3 or 4 at Post-baseline in Hematology Laboratory Test Values Based on CTCAE Grade	Blood and urine samples for the laboratory tests. A central laboratory will perform all clinical laboratory assessments. Baseline was the last available assessment performed prior to the study intervention start date/time.; Grade 4 was not applicable for the parameters of anemia, hemoglobin increased, leukocytosis and lymphocyte count increased as Grade 4 was not defined for these 4 parameters per CTCAE version 4.03.	Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days in Subsequent Cycles, End of Treatment (EOT) ±3 Days and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months)
Secondary	Number of Participants With Shifts From Grade =2 at Baseline to Grade 3 or 4 at Post-baseline in Chemistry Laboratory Test Values Based on CTCAE Grade	Blood and urine samples for the laboratory tests. A central laboratory will perform all clinical laboratory assessments. Baseline was the last available assessment performed prior to the study intervention start date/time.; Grade 4 was not applicable for the parameters of hyperglycemia and hypoalbuminemia as Grade 4 was not defined for these 2 parameters per CTCAE version 4.03.	Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days in Subsequent Cycles, EOT ±3 Days and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months)
Secondary	Number of Participants With Notable Abnormal Vital Signs	Vital sign measurements were taken before blood collection for laboratory tests or at least 30 minutes after blood collection for laboratory tests, and were measured per institutional standards. Vital sign assessments included temperature, pulse rate, respiratory rate, and blood pressure (assessed in a recumbent, semi recumbent, or sitting position).; The criteria of notably abnormal vital signs are listed below: Systolic blood pressure (mmHg): high: =160 mmHg with increase from baseline of =20 mmHg; low: =90 mmHg with decrease from baseline of =20 mmHg.; Diastolic blood pressure (mmHg): high: =100 mmHg with increase from baseline of =15 mmHg; low: =50 mmHg with decrease from baseline of =15 mmHg.; Pulse rate (bpm): high: =120 bpm with increase from baseline of =15 bpm; low: =50 bpm with decrease from baseline of =15 bpm.; Weight (kg): high: =10% increase from baseline; low: =20% decrease from baseline.; Temperature (°C): high: =37.5 °C; low: =36 °C.	Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Day 1 ±3 Days of Subsequent Cycles, EOT ±3 Days, and Safety Follow-up Visit (30 Days [±7 Days] After the EOT Visit) (Up to 36 Months)
Secondary	Number of Participants With Notable ECG (QTcF) Values	The QTcF increase from baseline >30/60 msec and new QTcF >450/480/500 msec were defined as clinically notable ECG criteria. Triplicate ECG measurements were obtained. For new abnormal post-baseline values, the table below presents the number of participants with both non-missing baseline and post-baseline values, and baseline values not meeting the criteria. For abnormal changes from baseline, the table below presents the number of participants with both non-missing baseline and post-baseline evaluations. Baseline was defined as the average of the machine-read triplicate ECG measurements taken pre-dose on Day 1. Change from baseline was post-baseline - baseline values.	Screening, Cycle 1 Day 1, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months)
Secondary	Number of Participants With the Worst Post-baseline Left Ventricular Ejection Fraction (LVEF) Values Based on CTCAE Grade	Cardiac ejection fraction was assessed by transthoracic echocardiogram (ECHO) or multigated acquisition (MUGA). Participants who developed signs/symptoms of congestive heart failure (CHF) at any point during the study were required to have an evaluation of LVEF measurements by ECHO or MUGA and were monitored per institutional guidelines.; Participants were considered as having a LVEF abnormality if the worst post-value was CTCAE Grade 2, 3 or 4 according to the following classification: Grade 0: Non-missing value below Grade 2. Grade 2: LVEF between 40% and 50%, inclusive, or absolute change from baseline between -10% and < -20%.; Grade 3: LVEF between 20% and 39%, inclusive, or absolute change from baseline = -20%.; Grade 4: LVEF lower than 20%. Baseline was defined as the last available and valid assessment before or on the start date of study intervention.	Screening, Cycle 2 Day 1 ±3 Days, Every 12 Weeks ±7 Days, and EOT ±3 Days (Up to 36 Months)

External Links

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