Trial Outcomes & Findings for LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE) (NCT NCT02187783)

NCT ID: NCT02187783

Last Updated: 2019-07-18

Results Overview

Clinical benefit (CB) for patients with solid tumors were assessed using RECIST 1.1 and included responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to \<10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm. FAS

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 106 participants
• Primary outcome timeframe: Baseline up ≥16 weeks up to approximately 36 months
• Results posted on: 2019-07-18

Participant Flow

There were 176 patients screened

Participant milestones

Measure	Ribociclib 600 mg LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.
Overall Study STARTED	106
Overall Study Patients With Solid Tumors	105
Overall Study COMPLETED	0
Overall Study NOT COMPLETED	106

Reasons for withdrawal

Measure	Ribociclib 600 mg LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.
Overall Study Adverse Event	8
Overall Study Death	3
Overall Study Progressive disease	80
Overall Study Protocol Violation	3
Overall Study Physician Decision	2
Overall Study Withdrawal by Subject	9
Overall Study Study terminated by sponsor	1

Baseline Characteristics

LEE011 for Patients With CDK4/6 Pathway Activated Tumors (SIGNATURE)

Baseline characteristics by cohort

Measure	Ribociclib 600 mg n=106 Participants LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.
Age, Continuous	60.5 years STANDARD_DEVIATION 13.52 • n=5 Participants
Sex: Female, Male Female	56 Participants n=5 Participants
Sex: Female, Male Male	50 Participants n=5 Participants
Race/Ethnicity, Customized White	90 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	4 Participants n=5 Participants
Race/Ethnicity, Customized Asian	5 Participants n=5 Participants
Race/Ethnicity, Customized Other	7 Participants n=5 Participants
Primary tumor type Adrenals	1 Participants n=5 Participants
Primary tumor type Bladder	7 Participants n=5 Participants
Primary tumor type Breast-triple negative	7 Participants n=5 Participants
Primary tumor type Cervix	1 Participants n=5 Participants
Primary tumor type Cholangio	2 Participants n=5 Participants
Primary tumor type Chordoma	1 Participants n=5 Participants
Primary tumor type Colorectal	2 Participants n=5 Participants
Primary tumor type Esophagus	3 Participants n=5 Participants
Primary tumor type Gall bladder ducts	1 Participants n=5 Participants
Primary tumor type Gastroesophageal junction	4 Participants n=5 Participants
Primary tumor type Gastrointestinal stromal tumor	1 Participants n=5 Participants
Primary tumor type Head and neck non-squamous cell carcinoma	4 Participants n=5 Participants
Primary tumor type Head and neck squamous cell carcinoma	7 Participants n=5 Participants
Primary tumor type Kidneys	2 Participants n=5 Participants
Primary tumor type Liver	2 Participants n=5 Participants
Primary tumor type Lung non-small cell adenocarcinoma	9 Participants n=5 Participants
Primary tumor type Lung non-small cell non-adenocarcinoma	2 Participants n=5 Participants
Primary tumor type Lung non-small cell squamous	6 Participants n=5 Participants
Primary tumor type Lymphoma	1 Participants n=5 Participants
Primary tumor type Mesothelioma	5 Participants n=5 Participants
Primary tumor type Neuroendocrine	2 Participants n=5 Participants
Primary tumor type Ovarian	3 Participants n=5 Participants
Primary tumor type Pancreas	5 Participants n=5 Participants
Primary tumor type Penile	1 Participants n=5 Participants
Primary tumor type Prostate	1 Participants n=5 Participants
Primary tumor type Salivary gland	1 Participants n=5 Participants
Primary tumor type Sarcoma	13 Participants n=5 Participants
Primary tumor type Skin non-melanoma	3 Participants n=5 Participants
Primary tumor type Thyroid	1 Participants n=5 Participants
Primary tumor type Unknown primary	4 Participants n=5 Participants
Primary tumor type Uterus	4 Participants n=5 Participants
Number of participants who had radiotherapy, surgery and liver metastasis Prior antineoplastic radiotherapy	61 Participants n=5 Participants
Number of participants who had radiotherapy, surgery and liver metastasis Prior antineoplastic surgery	92 Participants n=5 Participants
Number of participants who had radiotherapy, surgery and liver metastasis Liver metastasis	29 Participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status for participants Performance status = 0	36 participants n=5 Participants
Eastern Cooperative Oncology Group (ECOG) Performance Status for participants Performance status = 1	70 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline up ≥16 weeks up to approximately 36 months

Clinical benefit (CB) for patients with solid tumors were assessed using RECIST 1.1 and included responses of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD) for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm. FAS

Outcome measures

Measure	Ribociclib 600 mg n=105 Participants LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.
Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments Complete response	0 Participants
Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments Partial response (PR)	3 Participants
Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments Stable disease (SD)	16 Participants
Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments Progressive disease (PD)	71 Participants
Number of Participants With Solid Tumor Response ≥ 16 Weeks for Based Upon Local Investigator Assessments Non-evaluable (NE)	15 Participants

PRIMARY outcome

Timeframe: Baseline and ≥ 16 weeks up to approximately 36 months

CBR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR + PR + SD for ≥ 16 weeks. CR and PR (for solid tumors) required a confirmation at least 4 weeks after the initial response observation. For hematologic tumors other appropriate hematological response criteria was applied. CR=Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have had reduction in short axis to <10 mm, PR=At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters, SD=Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study, PD=At least a 20% increase in the sum of diameter of all measured target lesions and also demonstrate an absolute increase of at least 5 mm FAS

Outcome measures

Measure	Ribociclib 600 mg n=105 Participants LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.
Clinical Benefit Rate (CBR) of ≥ 16 Weeks FAS	19 participant Interval 11.3 to 26.8

PRIMARY outcome

Timeframe: Baseline and ≥ 16 weeks up to approximately 36 months

ORR was determined by local, Investigator assessment for each tumor assessment and defined as responses of CR+PR ≥ 16 weeks. FAS

Outcome measures

Measure	Ribociclib 600 mg n=105 Participants LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.
Overall Response Rate (ORR) ≥ 16 Weeks. FAS	3 participant Interval 0.6 to 8.1

SECONDARY outcome

Timeframe: Every 8 weeks until death, assessed up to 24 months

Progression-free survival (PFS) is the time from the date of start of treatment to the date of event defined as the first documented progression or death due to any cause within 30 days of the last dose. If a subject has not had an event, progression-free survival is censored at the date of last adequate tumor assessment. Progressive disease is defined as at least a 20% increase in the sum of diameter of all measured target lesions, taking as reference the smallest sum of diameter of all target lesions recorded at or after baseline. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm (Note: the appearance of one or more new lesions is also considered progression)

Outcome measures

Measure	Ribociclib 600 mg n=106 Participants LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.
Progression Free Survival (PFS)	1.8 months Interval 1.8 to 1.9

SECONDARY outcome

Timeframe: Baseline up to approximately 36 months

Number of participants Overall survival (OS) is defined as the time from the date of first dose to the date of death due to any cause.

Outcome measures

Measure	Ribociclib 600 mg n=106 Participants LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.
Overall Survival (OS)	7.7 months Interval 5.3 to 9.2

SECONDARY outcome

Timeframe: Baseline up to approximately 36 months

Duration of response (DOR) is defined as time from the first documented response to the date first documented disease progression or relapse or death due to any cause. For patients with solid tumors the assessment criteria will be RECIST 1.1 and will include responses of CR and/or PR.

Outcome measures

Measure	Ribociclib 600 mg n=3 Participants LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.
Number of Days for Duration of Response for Responders Patient 1	254 Days
Number of Days for Duration of Response for Responders Patient 2	330 Days
Number of Days for Duration of Response for Responders Patient 3	985 Days

Adverse Events

Ribociclib 600 mg

Serious events: 40 serious events

Other events: 104 other events

Deaths: 14 deaths

Serious adverse events

Measure	Ribociclib 600 mg n=106 participants at risk LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.
Blood and lymphatic system disorders Anaemia	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Blood and lymphatic system disorders Febrile neutropenia	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Blood and lymphatic system disorders Thrombocytopenia	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Cardiac disorders Atrial fibrillation	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Cardiac disorders Cardio-respiratory arrest	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Cardiac disorders Palpitations	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Cardiac disorders Pericardial effusion	1.9% 2/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Abdominal pain	1.9% 2/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Abdominal pain upper	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Ascites	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Constipation	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Dysphagia	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Haemorrhoids	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Mouth haemorrhage	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Nausea	2.8% 3/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Small intestinal obstruction	1.9% 2/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Vomiting	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
General disorders Asthenia	1.9% 2/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
General disorders Non-cardiac chest pain	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
General disorders Pain	1.9% 2/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Infections and infestations Abscess	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Infections and infestations Peritonitis	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Infections and infestations Pneumonia	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Infections and infestations Pseudomonal sepsis	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Infections and infestations Pyelonephritis	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Infections and infestations Pyelonephritis acute	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Infections and infestations Sepsis	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Infections and infestations Urinary tract infection	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Alanine aminotransferase increased	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Aspartate aminotransferase increased	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Blood bilirubin increased	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Weight decreased	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Metabolism and nutrition disorders Diabetic ketoacidosis	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Metabolism and nutrition disorders Failure to thrive	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Metabolism and nutrition disorders Hypomagnesaemia	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Metabolism and nutrition disorders Hyponatraemia	1.9% 2/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Metabolism and nutrition disorders Hypophosphataemia	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Metabolism and nutrition disorders Malnutrition	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Musculoskeletal and connective tissue disorders Bone pain	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Musculoskeletal and connective tissue disorders Muscular weakness	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Musculoskeletal and connective tissue disorders Pain in extremity	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Cancer pain	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Nervous system disorders Aphasia	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Nervous system disorders Embolic stroke	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Nervous system disorders Transient ischaemic attack	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Psychiatric disorders Confusional state	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Psychiatric disorders Mental status changes	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Renal and urinary disorders Nephropathy toxic	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Renal and urinary disorders Renal failure	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Renal and urinary disorders Renal tubular necrosis	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Renal and urinary disorders Ureteric obstruction	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Respiratory, thoracic and mediastinal disorders Acute respiratory failure	1.9% 2/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	4.7% 5/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Respiratory, thoracic and mediastinal disorders Pulmonary embolism	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Respiratory, thoracic and mediastinal disorders Respiratory failure	1.9% 2/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Vascular disorders Deep vein thrombosis	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Vascular disorders Hypotension	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Vascular disorders Thrombophlebitis superficial	0.94% 1/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.

Other adverse events

Measure	Ribociclib 600 mg n=106 participants at risk LEE011 600 mg (hard gelatin capsules) was administered orally once daily for 3 weeks on/1 week off. A complete treatment cycle was defined as 28 days.
Blood and lymphatic system disorders Anaemia	24.5% 26/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Blood and lymphatic system disorders Leukopenia	11.3% 12/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Blood and lymphatic system disorders Neutropenia	31.1% 33/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Blood and lymphatic system disorders Thrombocytopenia	12.3% 13/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Abdominal pain	9.4% 10/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Constipation	19.8% 21/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Diarrhoea	26.4% 28/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Dyspepsia	7.5% 8/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Nausea	43.4% 46/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Gastrointestinal disorders Vomiting	29.2% 31/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
General disorders Asthenia	7.5% 8/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
General disorders Chest pain	7.5% 8/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
General disorders Fatigue	42.5% 45/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
General disorders Oedema peripheral	11.3% 12/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
General disorders Pyrexia	7.5% 8/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Infections and infestations Urinary tract infection	10.4% 11/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Alanine aminotransferase increased	10.4% 11/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Aspartate aminotransferase increased	10.4% 11/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Blood alkaline phosphatase increased	7.5% 8/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Blood creatinine increased	14.2% 15/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Electrocardiogram QT prolonged	11.3% 12/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Gamma-glutamyltransferase increased	8.5% 9/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Lymphocyte count decreased	7.5% 8/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Neutrophil count decreased	15.1% 16/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Platelet count decreased	8.5% 9/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations Weight decreased	8.5% 9/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Investigations White blood cell count decreased	17.9% 19/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Metabolism and nutrition disorders Decreased appetite	19.8% 21/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Metabolism and nutrition disorders Dehydration	6.6% 7/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Metabolism and nutrition disorders Hyperglycaemia	8.5% 9/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Metabolism and nutrition disorders Hypoalbuminaemia	6.6% 7/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Metabolism and nutrition disorders Hypokalaemia	6.6% 7/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Metabolism and nutrition disorders Hypomagnesaemia	8.5% 9/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Musculoskeletal and connective tissue disorders Arthralgia	7.5% 8/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Musculoskeletal and connective tissue disorders Back pain	11.3% 12/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Musculoskeletal and connective tissue disorders Muscular weakness	6.6% 7/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Musculoskeletal and connective tissue disorders Musculoskeletal pain	7.5% 8/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Musculoskeletal and connective tissue disorders Myalgia	5.7% 6/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Musculoskeletal and connective tissue disorders Pain in extremity	6.6% 7/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Nervous system disorders Dizziness	12.3% 13/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Nervous system disorders Headache	8.5% 9/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Psychiatric disorders Anxiety	6.6% 7/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Psychiatric disorders Confusional state	5.7% 6/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Psychiatric disorders Insomnia	10.4% 11/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Renal and urinary disorders Proteinuria	5.7% 6/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Respiratory, thoracic and mediastinal disorders Cough	14.2% 15/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Respiratory, thoracic and mediastinal disorders Dyspnoea	18.9% 20/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Respiratory, thoracic and mediastinal disorders Epistaxis	5.7% 6/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	5.7% 6/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.
Skin and subcutaneous tissue disorders Rash	5.7% 6/106 • Adverse Events (AEs) were collected from First Patient First Visit (FPFV) until Last Patient Last Visit (LPLV). All AEs reported in this record are from date of First Patient First Treatment until Last Patient Last Visit) which was an average of 2.7 months up to maximum of 36.2 months.

Additional Information

Study Director

Novartis Pharmaceuticals

Phone: 1-888-669-6682

Email: Novartis.email@novartis.com

Results disclosure agreements

• Principal investigator is a sponsor employee The terms and conditions of Novartis' agreements with its investigators may vary. However, Novartis does not prohibit any investigator from publishing. Any publications from a single-site are postponed until the publication of the pooled data (ie, data from all sites) in the clinical trial.
• Publication restrictions are in place

Restriction type: OTHER