Trial Outcomes & Findings for Study of LY2835219 for Mantle Cell Lymphoma (NCT NCT01739309)

Last Updated: 2023-09-21

Results Overview

The DCR was estimated based on the Response Criteria for Non-Hodgkin's Lymphomas (Cheson et al. 1999). DCR was assessed from date of first dose until disease progression or death or start of new anticancer therapy. CR is defined as the disappearance of all detectable clinical and radiographic evidence of disease and disappearance of all disease-related symptoms based on CT scan or bone marrow biopsy; CRu = the CR criteria is met and a residual lymph node mass greater than 1.5 cm in greatest transverse diameter that has regressed by more than 75% in the sum of the product diameter (SPD). PR is \>= 50% decrease in SPD of the six largest nodal masses/no new sites of disease. Progressive Disease (PD) is defined as an increase by 25% in longest diameter, new lesion or assessable disease progression. SD=small changes not meeting the above criteria; DCR and its exact 95% confidence interval (CI) was estimated for treated participants using the Clopper-Pearson method.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

28 participants

Primary outcome timeframe

From Date of First Dose until Disease Progression or Death or Start of New Anticancer Therapy (Up to 28 Months)

Results posted on

2023-09-21

Participant Flow

Completers are those who died, or are alive and being followed at the end of the trial but off treatment.

Participant milestones

Participant milestones
Measure	Abemaciclib 200 milligram (mg) of Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle
Overall Study STARTED	28
Overall Study Received at Least One Dose of Study Drug	28
Overall Study COMPLETED	26
Overall Study NOT COMPLETED	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Abemaciclib 200 milligram (mg) of Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle
Overall Study Adverse Event	1
Overall Study Withdrawal by Subject	1

Baseline Characteristics

Study of LY2835219 for Mantle Cell Lymphoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Abemaciclib n=28 Participants 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle
Age, Continuous	68.4 years STANDARD_DEVIATION 7.8 • n=5 Participants
Sex: Female, Male Female	11 Participants n=5 Participants
Sex: Female, Male Male	17 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	28 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	27 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants
Region of Enrollment France	13 Participants n=5 Participants
Region of Enrollment Germany	15 Participants n=5 Participants

PRIMARY outcome

Timeframe: From Date of First Dose until Disease Progression or Death or Start of New Anticancer Therapy (Up to 28 Months)

Population: All participants who received at least one dose of study drug and had evaluable DCR data.

Outcome measures

Outcome measures
Measure	Abemaciclib n=28 Participants 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Percentage of Participants Who Achieve Disease Control Rate (DCR) Which Includes Complete Response (CR), Complete Response Unconfirmed (CRu), Partial Response (PR) or Stable Disease (SD)	71.4 percentage of participants Interval 51.3 to 86.8

SECONDARY outcome

Timeframe: From Date of First Dose until Disease Progression (Up to 28 Months)

Population: All participants who received at least one dose of study drug and had evaluable BOR data.

BOR was assessed based on the Response Criteria for Non-Hodgkin's Lymphomas and was measured from date of first dose until the earliest evidence of objective progression or start of new anticancer therapy. Any responses observed after objective progression or after the start of new anticancer therapy are excluded from the determination of best response. A second confirmatory radiological tumor assessment was performed at least 28 days after the first evidence of response (CR, CRu, or PR). Two objective status determinations of CR (or CRu) before progression were required for a best response of CR (or CRu). Two determinations of PR or better before progression, but not qualifying for CR or CRu, were required for a best response of PR.

Outcome measures

Outcome measures
Measure	Abemaciclib n=28 Participants 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Percentage of Participants Who Achieve Best Overall Disease Response (BOR) That Includes CR, CRu or PR	35.7 percentage of participants Interval 18.6 to 55.9

SECONDARY outcome

Timeframe: From Date of CR, CRu or PR until Disease Progression or Death Due to Any Cause (Up to 28 Months)

Population: All participants who received at least one dose of study drug and achieved BOR. 4 participants were censored.

DOR is from the date when criteria for objective response (ie, CR, CRu or PR) are met, to the first documentation of relapse or disease progression or death due to any cause. DOR is based on the Response Criteria for Non-Hodgkin's Lymphomas of the Cancer and Leukemia Group B. CR is defined as disappearance of all disease, no symptoms and must last 4 weeks or "unconfirmed CR, (CRu)". PR is defined as \>= 50% decrease in sum of product diameter (SPD), no increase or new lesion, or assessable disease stable or decreased, must last 4 weeks or CRu. Progressive Disease or PD is defined as an increase by 25% in longest diameter, new lesion, or assessable disease progression. DOR was analyzed using Kaplan-Meier methods. If the participant receives other anticancer therapy prior to progression, the participant was censored at the start date of this other therapy.

Outcome measures

Outcome measures
Measure	Abemaciclib n=10 Participants 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Duration of Objective Response (DOR)	12.39 months Interval 3.19 to The upper limit of the 95% CI was not calculated due to the high censoring rate.

SECONDARY outcome

Timeframe: From Date of First Dose until Disease Progression or Death Due to Any Cause (Up to 28 Months)

Population: All participants who received at least one dose of study drug. 9 participants were censored.

PFS is defined as the date of first dose until disease progression or death due to any cause based on the Response Criteria for Non-Hodgkin's Lymphomas. Disease progression is defined as the first date of documentation of a new lesion or enlargement of a previous lesion, or the date after radiologic assessment has been completed. PD is defined as an increase by 25% in longest diameter, new lesion, or assessable disease progression. Progression-free survival was analyzed using Kaplan-Meier methods. If the participant receives other anticancer therapy prior to progression, the participant was censored at the start date of this other therapy.

Outcome measures

Outcome measures
Measure	Abemaciclib n=28 Participants 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Progression-Free Survival (PFS)	8.18 Months Interval 4.34 to 16.03

SECONDARY outcome

Timeframe: From Date of First Dose until Death Due to Any Cause (Up to 28 Months)

Population: All participants who received at least one dose of study drug.

OS is defined as from the date of first dose until death due to any cause. For each participant who is not known to have died as of the data-inclusion cutoff date for overall survival analysis, OS were censored on the last date the participant is known to be alive. Overall survival was analyzed using Kaplan-Meier methods.

Outcome measures

Outcome measures
Measure	Abemaciclib n=28 Participants 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Overall Survival (OS)	16.03 Months Interval 6.77 to The 95% confidence interval upper limit was not reached (NR).

SECONDARY outcome

Timeframe: From Date of First Dose until Disease Progression, Discontinuation of Treatment, or Death Due to Any Cause (Up to 28 Months)

Population: All participants who received at least one dose of study drug.

Event-free survival (time to treatment failure) is measured from date of first dose to disease progression, or discontinuation of treatment for any reason (eg, disease progression, toxicity, participant preference, initiation of new treatment without documented progression, or death due to any cause). 2 participants were censored. Event-free survival is defined only for responders (participants with a CR, CRu, or PR).

Outcome measures

Outcome measures
Measure	Abemaciclib n=28 Participants 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Event-Free Survival	11.29 Months Interval 5.45 to 16.26

SECONDARY outcome

Timeframe: From Date of First Dose Until Disease Progression (Up to 28 Months)

Population: All participants who received at least one dose of study drug. 17 participants were censored.

Time to Disease Progression is based on the response criteria of Non-Hodgkin's Lymphomas. Time to progression (TTP) is defined as the time from date of first dose until documented disease progression or death as a result of lymphoma. In TTP, deaths from other causes are censored either at the time of death or at an earlier time of assessment.

Outcome measures

Outcome measures
Measure	Abemaciclib n=28 Participants 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Time to Disease Progression	12.85 Months Interval 5.45 to The upper limit was not calculated due to the high censoring rate.

SECONDARY outcome

Timeframe: First Dose Until Date of Disease Progression or Time of Occurrence Disease-Free State or CR to Disease Recurrence or Death (Up to 28 Months)

Population: All participants who received at least one dose of study drug. 5 participants were censored.

Disease-free survival is measured from first dose until date of disease progression or the time of occurrence of disease-free state or attainment of a CR to disease recurrence or death as a result of lymphoma or acute toxicity of treatment. Progressive Disease (PD) is defined as an increase by 25%, new lesion, or accessible progressive disease. Disease-Free Survival was assessed based on the response criteria of Non-Hodgkins Lymphomas. Disease-free survival is only defined for participants with response.

Outcome measures

Outcome measures
Measure	Abemaciclib n=28 Participants 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Disease-Free Survival	9.20 Months Interval 3.19 to The 95% confidence interval upper limit was not reached (NR).

SECONDARY outcome

Timeframe: Baseline, Cycle 5 (Up To Day 140)

Population: All participants who received at least one dose of study drug and had baseline and post baseline FACT-Lym data.

Change From Baseline in FACT-Lym Total Outcome Index (TOI) Score (Follicular Lymphoma Population). The FACT-Lym TOI Score for the follicular lymphoma population was derived from the following 3 individual FACT-Lym questionnaire subscale scores: Physical Well-being (range: 0-28), Functional Well-being (range: 0-28) and Lymphoma (range: 0-60). The FACT-Lym TOI Score is the sum of the 3 individual subscales (range 0-116). Higher scores indicate better outcomes and lower scores indicate worse outcomes. A positive change from baseline indicates an improvement and a negative change is a detriment.

Outcome measures

Outcome measures
Measure	Abemaciclib n=13 Participants 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores Physical Well-Being (PWB) Subscale Score	0.2 units on a scale Standard Deviation 5.6
Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores Functional (FWB) Subscale Score	-0.9 units on a scale Standard Deviation 4.5
Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores LYM Subscale Score	1.1 units on a scale Standard Deviation 5.2
Change From Baseline in Functional Assessment of Cancer Therapy - Lymphoma (FACT-Lym) TOI and Subscale Scores FACT-Lym TOI Score	0.5 units on a scale Standard Deviation 12.5

SECONDARY outcome

Timeframe: Predose, 1 hour (hr), 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose

Population: All participants who received at least one dose of study drug and had evaluable PK data.

Outcome measures

Outcome measures
Measure	Abemaciclib n=26 Participants 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
Pharmacokinetics (PK): Maximum Concentration (Cmax) of Abemaciclib	189 nanogram/milliliter (ng/ml) Geometric Coefficient of Variation 59

SECONDARY outcome

Timeframe: Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose

Population: All randomized who received at least one dose of study drug and had evaluable PK data.

Outcome measures

Outcome measures
Measure	Abemaciclib n=26 Participants 200 mg Abemaciclib was administered orally every 12 hours on days 1 through 28 of a 28-day cycle.
PK - Area Under the Concentration-Time Curve From Zero to Last Time Point (AUC[0-tlast]) of Abemaciclib	978 hournanogram/milliliter (hrng/ml) Geometric Coefficient of Variation 61

SECONDARY outcome

Timeframe: Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose

Population: Zero participants were analyzed due to the calculation of half-life (t1/2) by noncompartmental analysis was not possible due to cessation of sampling at 8 hours postdose.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose

Population: Zero participants were analyzed. Vd was not calculated by non-compartmental analysis with the available data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Predose, 1 hr, 2 hr, 4 hr, 6 hr, 8 hr, 10 Hours Postdose

Population: Zero participants were analyzed. CL was not calculated due to PK sampling schedule was not suitable for estimation of these PK parameters.

Outcome measures

Outcome data not reported

Adverse Events

Abemaciclib

Serious events: 13 serious events

Other events: 28 other events

Deaths: 23 deaths

Serious adverse events

Serious adverse events
Measure	Abemaciclib n=28 participants at risk 200 milligram (mg) Abemaciclib administered orally every 12 hours on days 1 through 28 of a 28-day cycle
Blood and lymphatic system disorders Anaemia	7.1% 2/28 • Number of events 2 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Gastrointestinal disorders Ileus	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Gastrointestinal disorders Rectal haemorrhage	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
General disorders General physical health deterioration	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
General disorders Pyrexia	3.6% 1/28 • Number of events 2 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Infections and infestations Device related infection	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Infections and infestations Meningitis	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Infections and infestations Pneumonia	7.1% 2/28 • Number of events 3 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Infections and infestations Progressive multifocal leukoencephalopathy	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Infections and infestations Sepsis	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Infections and infestations Septic shock	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Fall	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Injury, poisoning and procedural complications Head injury	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Dehydration	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Back pain	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Nervous system disorders Nervous system disorder	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Nervous system disorders Somnolence	3.6% 1/28 • Number of events 1 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.

Other adverse events

Other adverse events
Measure	Abemaciclib n=28 participants at risk 200 milligram (mg) Abemaciclib administered orally every 12 hours on days 1 through 28 of a 28-day cycle
Blood and lymphatic system disorders Anaemia	28.6% 8/28 • Number of events 8 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Leukopenia	10.7% 3/28 • Number of events 5 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Neutropenia	25.0% 7/28 • Number of events 8 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Blood and lymphatic system disorders Thrombocytopenia	39.3% 11/28 • Number of events 12 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Gastrointestinal disorders Abdominal pain	14.3% 4/28 • Number of events 5 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Gastrointestinal disorders Diarrhoea	75.0% 21/28 • Number of events 31 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Gastrointestinal disorders Nausea	32.1% 9/28 • Number of events 14 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Gastrointestinal disorders Vomiting	28.6% 8/28 • Number of events 56 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
General disorders Asthenia	7.1% 2/28 • Number of events 3 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
General disorders Fatigue	35.7% 10/28 • Number of events 15 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
General disorders Oedema peripheral	21.4% 6/28 • Number of events 8 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
General disorders Pyrexia	14.3% 4/28 • Number of events 5 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Infections and infestations Bronchitis	21.4% 6/28 • Number of events 6 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Infections and infestations Conjunctivitis	14.3% 4/28 • Number of events 4 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Infections and infestations Nasopharyngitis	7.1% 2/28 • Number of events 4 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Infections and infestations Rhinitis	7.1% 2/28 • Number of events 2 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Infections and infestations Urinary tract infection	14.3% 4/28 • Number of events 6 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Investigations Blood creatinine increased	25.0% 7/28 • Number of events 9 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Investigations Gamma-glutamyltransferase increased	7.1% 2/28 • Number of events 9 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Investigations Neutrophil count decreased	14.3% 4/28 • Number of events 12 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Investigations Platelet count decreased	10.7% 3/28 • Number of events 4 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Investigations Weight decreased	7.1% 2/28 • Number of events 2 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Decreased appetite	14.3% 4/28 • Number of events 4 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Metabolism and nutrition disorders Hyperkalaemia	7.1% 2/28 • Number of events 2 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Musculoskeletal and connective tissue disorders Muscle spasms	7.1% 2/28 • Number of events 2 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Nervous system disorders Dizziness	14.3% 4/28 • Number of events 4 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Nervous system disorders Dysgeusia	7.1% 2/28 • Number of events 2 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Nervous system disorders Headache	10.7% 3/28 • Number of events 3 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Nervous system disorders Presyncope	7.1% 2/28 • Number of events 2 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Cough	14.3% 4/28 • Number of events 4 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Respiratory, thoracic and mediastinal disorders Dyspnoea	17.9% 5/28 • Number of events 5 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Alopecia	10.7% 3/28 • Number of events 3 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Night sweats	7.1% 2/28 • Number of events 4 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Skin and subcutaneous tissue disorders Pruritus	10.7% 3/28 • Number of events 3 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.
Vascular disorders Hypotension	7.1% 2/28 • Number of events 2 • Baseline till end of follow-up (Up to 7.9 years) All participants who received at least one dose of study drug.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60