TRADE: Dose Escalation Tolerability of Abemaciclib in HR+... | NCT06001762

Name	Class
Eli Lilly and Company	INDUSTRY

Label	Type	Description	Intervention Names
Abemaciclib	Experimental	Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection.	Drug: Abemaciclib Drug: Tamoxifen Drug: Anastrozole Drug: Letrozole Drug: Exemestane Drug: LHRH Agonist

Name	Type	Description	Arm Group Labels	Other Names
Abemaciclib	Drug	CDK4 and CDK6 inhibitor, tablet taken orally	Abemaciclib

Measure	Description	Time Frame
Composite Endpoint: Number of Participants With Abemaciclib Discontinuation for Any Reason, Abemaciclib Dose Reductions, or the Inability of Study Participants to Reach the Target Dose of Abemaciclib (Full Dose 150 mg BID) at 3 Months (12 Weeks)	The composite endpoint is the number and proportion of participants with abemaciclib discontinuation for any reason and/or abemaciclib dose reductions and/or the inability of study participants to reach the target dose of abemaciclib (full dose 150 mg BID) at 3 months (12 weeks).	3 months (12 weeks)

Measure	Description	Time Frame
Number of Participants Unable to Reach Full Dose of Abemaciclib at 3 Months (12 Weeks)	Number of participants unable to reach the full dose (150 mg BID) of abemaciclib at 3 months (12 weeks)	3 months (12 weeks)
Number of Participants Who Discontinued Abemaciclib Treatment for Any Reason at 12 Weeks

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Stage II or III node-positive HR+/HER2- breast cancer per local laboratory assessment.
Eligible participants must be appropriate candidates for adjuvant abemaciclib, per assessment of their treating physician.
Participants must be candidates for adjuvant endocrine therapy, which may have started before or at time of entry onto the trial. Patient may be receiving adjuvant aromatase inhibitor or tamoxifen, +/- ovarian suppression.
Participants must have undergone definitive surgery of the primary breast tumor(s) within 16 months of study entry.
At least 21 days must have elapsed between last dose of chemotherapy and registration. Participants who previously received chemotherapy must have recovered (Common Terminology Criteria for Adverse Events [CTCAE] Grade ≤1) from the acute effects of chemotherapy except for residual alopecia or Grade 2 peripheral neuropathy prior to randomization.
At least 14 days must have elapsed between end of radiotherapy and day 1 of treatment with abemaciclib. Participants who received prior radiotherapy must have completed and fully recovered from the acute effects of radiotherapy. No radiotherapy should be planned to occur during study therapy.
At least 14 days must have elapsed since most recent breast surgery prior to registration and patient has recovered from side effects of prior surgery.
Bilateral or multifocal/multicentric breast cancers that meet eligibility criteria are allowed.
ECOG performance status 0-1
Men and women with any menopausal status ≥18 years of age
Adequate organ function as defined below:
- Absolute neutrophil count (ANC) ≥ 1500 x 10^9/L
- Platelets ≥ 100 x 10^9/L
- Hemoglobin ≥ 8g/dL; patients may receive erythrocyte transfusions to achieve this hemoglobin level at the discretion of the investigator. Initial treatment must not begin earlier than the day after the erythrocyte transfusion.
- Bilirubin ≤ 1.5 x ULN. For patients with Gilbert syndrome, the limit is ≤ 2 x institutional ULN AND direct bilirubin within the normal range of normality.
- AST/ALT ≤ 3 x institutional ULN
Premenopausal women must have a negative serum or urine pregnancy test. Pregnancy testing does not need to be pursued in female patients who are:
- Age > 60 years; or
- Age < 60 with intact uterus and amenorrhea for 12 consecutive months or more AND FSH/estradiol levels within postmenopausal range; or
- Status-post bilateral oophorectomy, total hysterectomy, or bilateral tubal ligation.
Women of child-bearing potential and men with partners of childbearing potential must be willing to employ one highly effective form of nonhormonal contraception (with the exception of hormonal IUDs) or two effective forms of nonhormonal contraception by the patient and/or partner and continue its use for the duration of the study treatment and for 3 months after the last dose of abemaciclib.
Subject must be able to swallow and retain oral medication.
Ability to understand and the willingness to sign a written informed consent document.
Non-English-speaking patients are eligible but will be exempt from patient-completed questionnaires.

Exclusion Criteria:

Prior treatment with any CDK4/6 inhibitor.
Patients with node-negative breast cancer are not eligible for the trial.
Concurrent therapy with other investigational agents.
Diagnosis of inflammatory breast cancer (T4d).
History of allergic reactions attributed to abemaciclib or similar chemical or biologic composition or excipients.
Participants with a history of malignancy are ineligible except in the following circumstances:

--Individuals with a history of invasive breast cancer are not eligible unless they have been disease-free for a minimum of five years.
Individuals with a malignancy history other than invasive breast cancer are eligible if they have no active malignancy and are deemed by the investigator to be at low risk for recurrence of that malignancy.
Individuals with the following cancer history are eligible: adequately treated non- melanoma skin cancers, curatively treated in situ cancer of the cervix, ductal carcinoma in situ (DCIS) of the breast, stage 1 grade 1 endometrial carcinoma. Other exceptions may exist following review with the sponsor-investigator
Serious and/or uncontrolled preexisting medical condition(s) that, in the judgment of the investigator, would preclude participation in this study (for example, interstitial lung disease, severe dyspnea at rest or requiring oxygen therapy, severe renal impairment [e.g. estimated creatinine clearance <30ml/min], history of major surgical resection involving the stomach or small bowel, or preexisting uncontrolled Crohn's disease or ulcerative colitis or a preexisting chronic condition resulting in baseline Grade 2 or higher diarrhea) or other conditions that in the opinion of the investigator limit compliance with study requirements.
History of any of the following conditions: syncope of cardiovascular etiology, ventricular arrhythmia of pathological origin (including, but not limited to, ventricular tachycardia and ventricular fibrillation), or sudden cardiac arrest.
Any of the following due to teratogenic potential of the study drugs:
- Pregnant women
- Nursing women
- Women of childbearing potential who are unwilling to employ adequate contraception (condoms, diaphragms, IUDS, surgical sterilization, abstinence, etc). Hormonal birth control methods are not permitted.
- Men who are unwilling to employ adequate contraception (condoms, surgical sterilization, abstinence, etc).
Receipt of an experimental treatment in a clinical trial within the last 30 days or 5 half-lives, whichever is longer, prior to enrollment, or is currently enrolled in any other type of medical research (for example: medical device) judged by the sponsor-investigator not to be scientifically or medically compatible with this study.
Active systemic bacterial infection (requiring intravenous [IV] antibiotics at time of initiating study treatment) or invasive/ systemic fungal infection\
For patients with known HIV infection, CD4 baseline count should be evaluated: patients with a CDK count ≥ 350 cells/uL can be enrolled. Participants should be on established anti-retroviral therapy (ART) for at least four weeks and have an HIV viral load less than 400 copies/mL prior to enrollment. Potential pharmacological interactions of the ART with abemaciclib and endocrine therapy must be reviewed, particularly for the effects on CYP3A4.
Patients with active or chronic Hepatitis B or C are eligible provided they meet liver function laboratory criteria and cannot be on any medication with a known interaction with the study agents.
Participants receiving any medications or substances that are strong inhibitors or inducers of CYP3A4, including selected herbals (e.g., hypericum) and food (e.g., grapefruit) known for pharmacological interactions, cannot be enrolled, due to interference with the dose-escalation, unless the food or supplement has been discontinued at least after an interval equivalent to 3-5 half-lives of the inhibitor.

Name	Affiliation	Role
Erica Mayer, MD, MPH	Dana-Farber Cancer Institute	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Stamford Hospital		Stamford	Connecticut	06904	United States
Eastern Maine Medical Center (Northern Light)

ID	Title	Description
FG000	Abemaciclib	The dose escalation strategy utilizes Abemaciclib dose levels of 50mg BID x 2 weeks, then 100mg bid x 2 weeks, then 150mg bid from C2D1 and onwards Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection. Abemaciclib: CDK4 and CDK6 inhibitor, tablet taken orally Tamoxifen: Selective estrogen receptor modulator, taken orally per institutional standard of care Anastrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Letrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Exemestane: Steroidal aromatase inhibitor, taken orally per institutional standard of care LHRH Agonist: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Jan 26, 2026

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

Composite Endpoint: Number of Participants With Abemaciclib Discontinuation for Any Reason, Abemaciclib Dose Reductions, or the Inability of Study Participants to Reach the Target Dose of Abemaciclib (Full Dose 150 mg BID) at 3 Months (12 Weeks)

The composite endpoint is the number and proportion of participants with abemaciclib discontinuation for any reason and/or abemaciclib dose reductions and/or the inability of study participants to reach the target dose of abemaciclib (full dose 150 mg BID) at 3 months (12 weeks).

Subjects who received at least one dose of abemaciclib and did not progress within 12 weeks of starting treatment. One (1) subject had a progression event within 12 weeks of starting treatment. Therefore, this subject is excluded from the primary endpoint analysis.

Posted

Count of Participants

Participants

3 months (12 weeks)

ID	Title	Description
OG000	Abemaciclib	The dose escalation strategy utilizes Abemaciclib dose levels of 50mg BID x 2 weeks, then 100mg bid x 2 weeks, then 150mg bid from C2D1 and onwards Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection. Abemaciclib: CDK4 and CDK6 inhibitor, tablet taken orally Tamoxifen: Selective estrogen receptor modulator, taken orally per institutional standard of care Anastrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Letrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Exemestane: Steroidal aromatase inhibitor, taken orally per institutional standard of care LHRH Agonist: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Units	Counts
Participants	OG00089

Title

Denominators

Categories

Title	Measurements
Abemaciclib discontinuation, dose reduction, and/or taking less than target dose at 12 weeks	OG00026
Achieved abemaciclib target dose at 12 weeks	OG00063

Group IDs	Group Description	Statistical Method	Statistical Comment	P-Value	P-Value Comment	Parameter Type	Parameter Value	Dispersion Type	Dispersion Value	Confidence Interval Sides	Confidence Interval %	CI Lower Limit	CI Upper Limit	CI Lower Limit Comment	CI Upper Limit Comment	Estimate Comment	Tested Non-Inferiority	Non-Inferiority Type	Non-Inferiority Comment	Other Analysis Description
OG000		One-sided binomial test		0.023	One-sided binomial test testing whether the reported composite adverse event rate is less than the null hypothesis rate of 40% (value estimated from monarchE trial data).	Percentage	29.2			2-Sided	90	21.3	38.2					Superiority

Secondary

Number of Participants Unable to Reach Full Dose of Abemaciclib at 3 Months (12 Weeks)

Number of participants unable to reach the full dose (150 mg BID) of abemaciclib at 3 months (12 weeks)

Posted

Count of Participants

Participants

3 months (12 weeks)

ID	Title	Description
OG000	Abemaciclib	The dose escalation strategy utilizes Abemaciclib dose levels of 50mg BID x 2 weeks, then 100mg bid x 2 weeks, then 150mg bid from C2D1 and onwards Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection. Abemaciclib: CDK4 and CDK6 inhibitor, tablet taken orally Tamoxifen: Selective estrogen receptor modulator, taken orally per institutional standard of care Anastrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Letrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Exemestane: Steroidal aromatase inhibitor, taken orally per institutional standard of care LHRH Agonist: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Secondary

Number of Participants Who Discontinued Abemaciclib Treatment for Any Reason at 12 Weeks

Number of participants who discontinued abemaciclib treatment for any reason 3 months (12 weeks)

Posted

Count of Participants

Participants

3 months (12 weeks)

ID	Title	Description
OG000	Abemaciclib	The dose escalation strategy utilizes Abemaciclib dose levels of 50mg BID x 2 weeks, then 100mg bid x 2 weeks, then 150mg bid from C2D1 and onwards Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection. Abemaciclib: CDK4 and CDK6 inhibitor, tablet taken orally Tamoxifen: Selective estrogen receptor modulator, taken orally per institutional standard of care Anastrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Letrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Exemestane: Steroidal aromatase inhibitor, taken orally per institutional standard of care LHRH Agonist: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Secondary

Number of Participants With Abemaciclib Dose Reductions at 12 Weeks

Number of participants with abemaciclib dose reductions at 3 months (12 weeks)

Posted

Count of Participants

Participants

3 months (12 weeks)

ID	Title	Description
OG000	Abemaciclib	The dose escalation strategy utilizes Abemaciclib dose levels of 50mg BID x 2 weeks, then 100mg bid x 2 weeks, then 150mg bid from C2D1 and onwards Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection. Abemaciclib: CDK4 and CDK6 inhibitor, tablet taken orally Tamoxifen: Selective estrogen receptor modulator, taken orally per institutional standard of care Anastrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Letrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Exemestane: Steroidal aromatase inhibitor, taken orally per institutional standard of care LHRH Agonist: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Secondary

Number of Participants Experiencing CTCAE v5.0 Treatment-emergent Grade 2-4 Diarrhea by 24 Weeks

Among all patients who received at least one dose of Abemaciclib, summarize the maximum treatment-emergent diarrhea adverse event reported per subject (across any dose level received) between the start of treatment and up to 24 weeks. Adverse events (AEs) are graded in a clinical setting utilizing CTCAE v5.0 criteria; AEs of grade 2 to 5 are systematically reported, while grade 1 AEs are not systematically reported, so subjects with no reported AEs (grade 0) and subjects with a maximum grade 1 AE are combined into a single category. AEs are considered treatment-emergent if they start at or after the first dose of Abemaciclib.

Grade 0 - no toxicity reported

Grade 1 - mild

Grade 2 - moderate

Grade 3 - severe

Grade 4 - life-threatening

Grade 5 - fatal (no cases of grade 5 diarrhea to report)

Subjects who received at least one dose of abemaciclib

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Abemaciclib	The dose escalation strategy utilizes Abemaciclib dose levels of 50mg BID x 2 weeks, then 100mg bid x 2 weeks, then 150mg bid from C2D1 and onwards Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection. Abemaciclib: CDK4 and CDK6 inhibitor, tablet taken orally Tamoxifen: Selective estrogen receptor modulator, taken orally per institutional standard of care Anastrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Letrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Exemestane: Steroidal aromatase inhibitor, taken orally per institutional standard of care LHRH Agonist: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Secondary

Number of Participants Experiencing CTCAE v5.0 Treatment-emergent Adverse Events by 24 Weeks

Among all patients who received at least one dose of Abemaciclib, summarize the maximum treatment-emergent adverse event (of any kind) reported per subject (across any dose level received) between the start of treatment and up to 24 weeks. Adverse events (AEs) are graded in a clinical setting utilizing CTCAE v5.0 criteria; AEs of grade 2 to 5 are systematically reported, while grade 1 AEs are not systematically reported, so subjects with no reported AEs (grade 0) and subjects with a maximum grade 1 AE are combined into a single category. AEs are considered treatment-emergent if they start at or after the first dose of Abemaciclib.

Grade 0 - no toxicity reported

Grade 1 - mild

Grade 2 - moderate

Grade 3 - severe

Grade 4 - life-threatening

Grade 5 - fatal (no cases of grade 5 toxicities)

Subjects who received at least one dose of abemaciclib

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Abemaciclib	The dose escalation strategy utilizes Abemaciclib dose levels of 50mg BID x 2 weeks, then 100mg bid x 2 weeks, then 150mg bid from C2D1 and onwards Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection. Abemaciclib: CDK4 and CDK6 inhibitor, tablet taken orally Tamoxifen: Selective estrogen receptor modulator, taken orally per institutional standard of care Anastrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Letrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Exemestane: Steroidal aromatase inhibitor, taken orally per institutional standard of care LHRH Agonist: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Secondary

The composite endpoint at 24 weeks is the number and proportion of participants with abemaciclib (abema) treatment discontinuations and/or abemaciclib dose reductions and/or participant inability to reach the target dose (full dose 150 mg BID) of abemaciclib at 24 weeks.

Subjects who received at least one dose of abemaciclib and did not progress within 24 weeks of starting treatment. One (1) subject had a progression event within 24 weeks of starting treatment (the same subject excluded from the primary endpoint analysis at 12 weeks). Therefore, this subject is excluded from this secondary endpoint analysis.

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Abemaciclib	The dose escalation strategy utilizes Abemaciclib dose levels of 50mg BID x 2 weeks, then 100mg bid x 2 weeks, then 150mg bid from C2D1 and onwards Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection. Abemaciclib: CDK4 and CDK6 inhibitor, tablet taken orally Tamoxifen: Selective estrogen receptor modulator, taken orally per institutional standard of care Anastrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Letrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Exemestane: Steroidal aromatase inhibitor, taken orally per institutional standard of care LHRH Agonist: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Secondary

Number of Participants Unable to Reach the Full Dose by 24 Weeks

Number of participants unable to reach the full dose will be reported as the rate of participants who have never reached the full dose of abemaciclib at 150mg BID by 24 weeks.

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Abemaciclib	The dose escalation strategy utilizes Abemaciclib dose levels of 50mg BID x 2 weeks, then 100mg bid x 2 weeks, then 150mg bid from C2D1 and onwards Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection. Abemaciclib: CDK4 and CDK6 inhibitor, tablet taken orally Tamoxifen: Selective estrogen receptor modulator, taken orally per institutional standard of care Anastrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Letrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Exemestane: Steroidal aromatase inhibitor, taken orally per institutional standard of care LHRH Agonist: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Secondary

Number of Participants Who Discontinued Abemaciclib Treatment for to Any Reason at 24 Weeks

Number of Participants who Discontinued Abemaciclib Treatment for to Any Reason at 24 Weeks (6 months)

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Abemaciclib	The dose escalation strategy utilizes Abemaciclib dose levels of 50mg BID x 2 weeks, then 100mg bid x 2 weeks, then 150mg bid from C2D1 and onwards Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection. Abemaciclib: CDK4 and CDK6 inhibitor, tablet taken orally Tamoxifen: Selective estrogen receptor modulator, taken orally per institutional standard of care Anastrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Letrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Exemestane: Steroidal aromatase inhibitor, taken orally per institutional standard of care LHRH Agonist: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Secondary

Number of Participants With Abemaciclib Dose Reductions at 24 Weeks

Number of Participants with Abemaciclib Dose Reductions at 24 Weeks (6 months)

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Abemaciclib	The dose escalation strategy utilizes Abemaciclib dose levels of 50mg BID x 2 weeks, then 100mg bid x 2 weeks, then 150mg bid from C2D1 and onwards Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection. Abemaciclib: CDK4 and CDK6 inhibitor, tablet taken orally Tamoxifen: Selective estrogen receptor modulator, taken orally per institutional standard of care Anastrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Letrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Exemestane: Steroidal aromatase inhibitor, taken orally per institutional standard of care LHRH Agonist: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Secondary

Number of Participants Unable to Maintain the Full Dose of Abemaciclib by 24 Weeks

Number of participants who reached the full dose of abemaciclib (150mg BID) but then had a dose reduction by 24 weeks

Posted

Count of Participants

Participants

Up to 24 weeks

ID	Title	Description
OG000	Abemaciclib	The dose escalation strategy utilizes Abemaciclib dose levels of 50mg BID x 2 weeks, then 100mg bid x 2 weeks, then 150mg bid from C2D1 and onwards Study procedures will be conducted as follows: Cycles 1 - 24 Days 1 - 28 of 28-day cycle: Predetermined dose of Abemaciclib 2 x per day. Endocrine therapy 1 x per day. In clinic visits with blood tests, questionnaires, and assessments: Day 1 of Cycles 1, 2, and 3 Day 15 of Cycles 1 and 2 Every three cycles after Cycle 3 Day 1. End of treatment visit with blood tests, questionnaires, assessments, and stool sample collection. Abemaciclib: CDK4 and CDK6 inhibitor, tablet taken orally Tamoxifen: Selective estrogen receptor modulator, taken orally per institutional standard of care Anastrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Letrozole: Non-steroidal aromatase inhibitor, taken orally per institutional standard of care Exemestane: Steroidal aromatase inhibitor, taken orally per institutional standard of care LHRH Agonist: Luteinizing hormone-releasing hormone agonist), taken orally per institutional standard of care

Secondary

Not Posted

Oct 2027

Up to 24 months

Participants

Secondary

Number of Participants Unable to Reach the Full Dose by 24 Months

Number of participants who have never reached the full dose of abemaciclib at 150mg BID by 24 months.

Not Posted

Oct 2027

Up to 24 months

Participants

Secondary

Number of Participants Who Discontinued Abemaciclib Treatment Due to Any Reason Prior to 24 Months

Number of Participants who Discontinued Abemaciclib Treatment Due to Any Reason prior to 24 Months (at completion of adjuvant abemaciclib therapy for all subjects).

Not Posted

Oct 2027

Up to 24 months

Participants

Secondary

Number of Participants With Abemaciclib Dose Reductions at 24 Months

Number of Participants with Abemaciclib Dose Reductions at 24 months (at completion of adjuvant abemaciclib therapy for all subjects).

Not Posted

Oct 2027

Up to 24 months

Participants

Secondary

Number of Participants Unable to Maintain the Full Dose of Abemaciclib by 24 Months

Number of participants who reached the full dose of abemaciclib (150mg BID) but then had a dose reduction by 24 months

Not Posted

Oct 2027

Up to 24 months

Participants

Secondary

Number of Participants Experiencing CTCAE v5.0 Treatment-emergent Grade 2-4 Diarrhea by 24 Months

Among all patients who received at least one dose of Abemaciclib, summarize the maximum treatment-emergent diarrhea adverse event reported per subject (across any dose level received) between the start of treatment and up to 24 months. Adverse events (AEs) are graded in a clinical setting utilizing CTCAE v5.0 criteria; AEs of grade 2 to 5 are systematically reported, while grade 1 AEs are not systematically reported, so subjects with no reported AEs (grade 0) and subjects with a maximum grade 1 AE are combined into a single category. AEs are considered treatment-emergent if they start at or after the first dose of Abemaciclib.

Grade 0 - no toxicity reported

Grade 1 - mild

Grade 2 - moderate

Grade 3 - severe

Grade 4 - life-threatening

Grade 5 - fatal

Not Posted

Oct 2027

Up to 24 months

Participants

Other Adverse Events

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Anemia	Blood and lymphatic system disorders	CTCAE (5.0)	Systematic Assessment	EG0008 affected90 at risk
Mitral valve disease	Cardiac disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Sinus tachycardia	Cardiac disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Vertigo	Ear and labyrinth disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Blurred vision	Eye disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Eye disorders - Other, specify	Eye disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Abdominal pain	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG00010 affected90 at risk
Anal fissure	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Constipation	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG00029 affected90 at risk
Dry mouth	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Dyspepsia	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0005 affected90 at risk
Flatulence	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Gastroesophageal reflux disease	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0003 affected90 at risk
Gastrointestinal pain	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Hemorrhoids	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Mucositis oral	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Nausea	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0009 affected90 at risk
Oral hemorrhage	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Rectal hemorrhage	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Stomach pain	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Vomiting	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0003 affected90 at risk
Edema limbs	General disorders and administration site conditions	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Fatigue	General disorders and administration site conditions	CTCAE (5.0)	Systematic Assessment	EG00024 affected90 at risk
Flu like symptoms	General disorders and administration site conditions	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Non-cardiac chest pain	General disorders and administration site conditions	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Pain	General disorders and administration site conditions	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Allergic reaction	Immune system disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Breast infection	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Folliculitis	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Infections and infestations - Other, specify	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Lung infection	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Nail infection	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Otitis media	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Rhinitis infective	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Sinusitis	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0003 affected90 at risk
Skin infection	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Upper respiratory infection	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Urinary tract infection	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0005 affected90 at risk
Vaginal infection	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Alanine aminotransferase increased	Investigations	CTCAE (5.0)	Systematic Assessment	EG0003 affected90 at risk
Aspartate aminotransferase increased	Investigations	CTCAE (5.0)	Systematic Assessment	EG0004 affected90 at risk
Creatinine increased	Investigations	CTCAE (5.0)	Systematic Assessment	EG0003 affected90 at risk
INR increased	Investigations	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Lymphocyte count decreased	Investigations	CTCAE (5.0)	Systematic Assessment	EG00011 affected90 at risk
Neutrophil count decreased	Investigations	CTCAE (5.0)	Systematic Assessment	EG00028 affected90 at risk
White blood cell decreased	Investigations	CTCAE (5.0)	Systematic Assessment	EG00015 affected90 at risk
Anorexia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment	EG0006 affected90 at risk
Hyperglycemia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Hypocalcemia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Hypokalemia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Hypophosphatemia	Metabolism and nutrition disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Arthralgia	Musculoskeletal and connective tissue disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Back pain	Musculoskeletal and connective tissue disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Muscle cramp	Musculoskeletal and connective tissue disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify	Neoplasms benign, malignant and unspecified (incl cysts and polyps)	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Dizziness	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0003 affected90 at risk
Dysgeusia	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Headache	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0006 affected90 at risk
Nystagmus	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Peripheral sensory neuropathy	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Vasovagal reaction	Nervous system disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Anxiety	Psychiatric disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Depression	Psychiatric disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Insomnia	Psychiatric disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Chronic kidney disease	Renal and urinary disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Breast pain	Reproductive system and breast disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Vaginal dryness	Reproductive system and breast disorders	CTCAE (5.0)	Systematic Assessment	EG0004 affected90 at risk
Vaginal hemorrhage	Reproductive system and breast disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Allergic rhinitis	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0003 affected90 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0006 affected90 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0005 affected90 at risk
Respiratory, thoracic and mediastinal disorders - Other, specify	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Rash maculo-papular	Skin and subcutaneous tissue disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Skin and subcutaneous tissue disorders - Other, specify	Skin and subcutaneous tissue disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Surgical and medical procedures - Other, specify	Surgical and medical procedures	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Hot flashes	Vascular disorders	CTCAE (5.0)	Systematic Assessment	EG0006 affected90 at risk
Hypertension	Vascular disorders	CTCAE (5.0)	Systematic Assessment	EG00015 affected90 at risk
Thromboembolic event	Vascular disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk

ID	Term
D009371	Neoplasms by Site
D009369	Neoplasms
D001941	Breast Diseases
D012871	Skin Diseases
D017437	Skin and Connective Tissue Diseases

ID	Term
C000590451	abemaciclib
D013629	Tamoxifen
D000077384	Anastrozole
D000077289	Letrozole
C056516	exemestane
D007987	Gonadotropin-Releasing Hormone

ID	Term
D013267	Stilbenes
D001597	Benzylidene Compounds
D001555	Benzene Derivatives
D006841	Hydrocarbons, Aromatic
D006844	Hydrocarbons, Cyclic
D006838	Hydrocarbons
D009930	Organic Chemicals
D009570	Nitriles
D014230	Triazoles
D001393	Azoles
D006573	Heterocyclic Compounds, 1-Ring
D006571	Heterocyclic Compounds
D010906	Pituitary Hormone-Releasing Hormones
D007028	Hypothalamic Hormones
D036361	Peptide Hormones
D006728	Hormones
D006730	Hormones, Hormone Substitutes, and Hormone Antagonists
D009479	Neuropeptides
D010455	Peptides
D000602	Amino Acids, Peptides, and Proteins
D009842	Oligopeptides
D009419	Nerve Tissue Proteins
D011506	Proteins

Term	Organ System	Source Vocabulary	Assessment Type	Statistical Information
Pericardial effusion	Cardiac disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Diarrhea	Gastrointestinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Lung infection	Infections and infestations	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Chronic kidney disease	Renal and urinary disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Cough	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Dyspnea	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Nasal congestion	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Pleural effusion	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Pneumonitis	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0002 affected90 at risk
Sore throat	Respiratory, thoracic and mediastinal disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk
Thromboembolic event	Vascular disorders	CTCAE (5.0)	Systematic Assessment	EG0001 affected90 at risk