Try our mobile app
New analyses from the Phase 3 monarchE trial of two years of Verzenio treatment in node-positive, high risk early breast cancer show similar efficacy across age groups and in patients who had dose adjustments with benefit maintained at four-year follow-up; overall quality of life during the Verzenio treatment period shown to be similar to endocrine therapy alone
Updated data from the Phase 1/2 BRUIN trial of Jaypirca in patients with covalent BTK inhibitor pre-treated relapsed or refractory MCL continue to demonstrate durable efficacy and no newly identified safety signals
INDIANAPOLIS, June 2, 2023 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced Verzenio® (abemaciclib; CDK4/6 inhibitor) and Jaypirca™ (pirtobrutinib; non-covalent (reversible) BTK inhibitor) data to be presented at the 2023 ASCO® Annual Meeting in Chicago, June 2 – 6, 2023. Presentations include new analyses from the Phase 3 monarchE trial of two years of Verzenio treatment in patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, high risk early breast cancer (EBC) and updated data from the Phase 1/2 BRUIN trial for an approved use of Jaypirca in patients with covalent BTK inhibitor pre-treated relapsed or refractory mantle cell lymphoma (MCL).
"These additional data on Verzenio and Jaypirca build on the evidence supporting the role each of these medicines play in improving the treatment paradigms for patients with node-positive, high risk early breast cancer and covalent BTK inhibitor pre-treated relapsed or refractory MCL, respectively," said David Hyman, M.D., chief medical officer, Loxo@Lilly. "Mature data for Verzenio reinforce its benefit in the node-positive, high risk adjuvant setting across age groups and these data should also provide comfort that the durable efficacy observed is not compromised when dose reductions are necessary. We also continue to be encouraged by these longer-term follow up data for Jaypirca and the potential for treatment to extend the time patients with relapsed or refractory MCL may benefit from BTK inhibition therapy."
New Analyses from the Verzenio monarchE TrialAn oral presentation (Abstract #501) will highlight efficacy and safety results from age-based subgroup analyses from the Phase 3 monarchE study of Verzenio in combination with endocrine therapy (ET) in patients with HR+, HER2-, node-positive EBC at a high risk of recurrence. Previously reported four-year data from monarchE demonstrated that, with all patients off Verzenio, Verzenio with ET compared to ET alone reduced the risk of recurrence by 34% and the risk of distant relapse by 34% in this node positive, high risk EBC population, with a persistent and growing benefit demonstrated beyond the two-year treatment period with Verzenio – supporting the goal of eradicating micrometastatic disease to prevent recurrence even after patients have completed treatment.1
The new analyses show similar efficacy across age groups and in patients who had dose adjustments. Adjuvant Verzenio plus ET demonstrated an absolute benefit in invasive disease-free survival (IDFS) rate of 5.9% in those age 65 and older (n=850) and 6.4% in patients under 65 (n=4,787). Rates of adverse events (AEs) were also similar between age groups; 54% of patients 65 and older experienced Grade 3 and above AEs compared with 49% of patients under 65. Dose adjustments due to AEs were more common in patients age 65 and older. The impact of dose adjustments was evaluated among all patients enrolled in monarchE, regardless of age. In this analysis, patients were classified into three equal-sized subgroups according to their relative dose intensity (RDI) of Verzenio. IDFS outcomes at four years were similar across RDI subgroups (RDI from lowest dose intensity group to highest: 87.1%, 86.4%, 83.7%), showing treatment benefit is maintained despite dose modifications.
Patient-reported quality of life (QoL) data collected at baseline, 3, 6, 12, 18, and 24 months during the treatment period will also be presented, across all patients in monarchE. These results demonstrated overall QoL scores were similar for patients taking Verzenio plus ET and patients taking ET alone and were maintained in all age subgroups during the two-year Verzenio treatment period.
"The long-term efficacy and safety results from these analyses of the monarchE trial further demonstrate the benefit of adding two years of Verzenio to ET in the adjuvant setting, showing similar efficacy regardless of age, and even for those who have undergone dose modifications," said Erika P. Hamilton, M.D., medical oncologist, director of Breast Cancer Research at Sarah Cannon Research Institute and an investigator on the monarchE clinical trial. "These data, combined with new patient-reported outcomes, support the role of two years of Verzenio as the standard of care for people with HR+, HER2- early breast cancer and will be important for informing Verzenio treatment management."
These Verzenio data will be shared in an oral presentation today during the Breast Cancer—Local/Regional/Adjuvant session from 2:45 – 5:45 p.m. CT.
Updated Jaypirca Data from the Phase 1/2 BRUIN StudyA poster presentation (Abstract #7514) will highlight efficacy data with a median survival follow-up time of two years for Jaypirca in relapsed or refractory MCL from the BRUIN Phase 1/2 clinical trial. The presentation uses a July 29, 2022 data cutoff date, providing an additional six months of follow-up from the data recently published in the Journal of Clinical Oncology and presented at the 2022 American Society of Hematology Annual Meeting.
The dataset includes the first 90 MCL patients enrolled who had received a prior covalent Bruton's tyrosine kinase (BTK) inhibitor. Patients had received a median of three prior lines of therapy (range 1-8). Efficacy and safety results were consistent with previously reported data. Jaypirca demonstrated an overall response rate (ORR) of 56.7% (95% CI: 45.8-67.1), a median duration of response (DOR) of 17.6 months (95% CI: 7.3-27.2), and a median progression-free survival (PFS) of 7.4 months (95% CI: 5.3-13.3). Response rates were consistent in patients with high-risk disease features, including blastoid/pleomorphic variants, elevated Ki-67 index, and TP53 mutations. In the MCL safety cohort (n=166), the most frequent treatment-emergent adverse events (TEAEs) were fatigue (31.3%), diarrhea (22.3%), and dyspnea (16.3%).
A second poster presentation (Abstract #7513) will highlight clinical safety data in patients with relapsed or refractory B-cell malignancies, inclusive of subtypes still under investigational use, from the Phase 1/2 BRUIN trial who received long-term (≥12 months) Jaypirca treatment. These safety data, based on longer-term Jaypirca therapy, are consistent with the overall safety profile, without evidence of new or worsening toxicity signals. In this long-term safety cohort (n=326), the most common TEAEs, regardless of attribution, were fatigue (32%), diarrhea (31%), COVID-19 (29%), contusion (26%), cough (25%), and back pain (21%). With continued treatment (median of 19 months), the rates of select AEs of special interest including atrial fibrillation remained low and did not show clinically meaningful increases, particularly Grade ≥3.
Both Jaypirca data presentations will be discussed on June 5 from 1:15 – 2:45 p.m. CT during the Hematologic Malignancies—Lymphoma and Chronic Lymphocytic Leukemia poster discussion session.
About the monarchE StudymonarchE was a global, randomized, open-label, two cohort, multicenter Phase 3 clinical trial that enrolled 5,637 adults with HR+, HER2-, node-positive EBC at high risk of recurrence. The study enrolled patients across more than 600 sites in 38 countries and is the only adjuvant study designed to investigate a CDK4/6 inhibitor in a high risk EBC population. To be enrolled in Cohort 1 (n=5,120), which is the FDA-approved population, patients had to have 4+ positive nodes or 1-3 positive nodes and at least one of the following: tumors that were ≥5 cm or Grade 3. Patients enrolled in Cohort 2 could not have met the eligibility criteria for Cohort 1. To be enrolled in Cohort 2 (n=517), patients had to have 1-3 positive nodes and Ki-67 score ≥20%. Patients in each cohort were randomized 1:1 to receive either Verzenio 150 mg twice daily plus standard-of-care adjuvant ET (Cohort 1, n=2,555; Cohort 2, n=253) or standard-of-care adjuvant ET alone (Cohort 1, n=2,565; Cohort 2, n=264) for 2 years. ET continued for at least 5 years if deemed medically appropriate. The primary endpoint was IDFS. Consistent with expert guidelines, IDFS was defined as the length of time before breast cancer comes back, any new cancer develops, or death.
About the BRUIN Phase 1/2 TrialThe BRUIN Phase 1/2 clinical trial is the ongoing first-in-human, global, multi-center evaluation of Jaypirca in patients with previously treated hematologic malignancies, including MCL.
The trial includes a Phase 1 dose-escalation phase, a Phase 1b combination arm, and a Phase 2 dose-expansion phase. The primary endpoint of the Phase 1 study is maximum tolerated dose (MTD)/recommended Phase 2 dose (RP2D). Secondary endpoints include safety, pharmacokinetics (PK), and preliminary efficacy measured by ORR for monotherapy. The primary endpoint of the Phase 1b study is safety of the drug combinations. The secondary endpoints are PK and preliminary efficacy measured by ORR for the drug combinations. The primary endpoint for the Phase 2 study is ORR as determined by an IRC. Secondary endpoints include ORR as determined by investigator, best overall response (BOR), DOR, PFS, overall survival (OS), safety, and PK.
About Verzenio® (abemaciclib)Verzenio® (abemaciclib) is approved to treat people with certain HR+, HER2- breast cancers in the adjuvant and advanced or metastatic setting. Verzenio is the first and only CDK4/6 inhibitor approved to treat node-positive, high risk early breast cancer (EBC) patients.2 The National Comprehensive Cancer Network® (NCCN®) recommends consideration of two years of abemaciclib (Verzenio) added to endocrine therapy as a Category 1 treatment option in the adjuvant setting.3
The collective results of Lilly's clinical development program continue to differentiate Verzenio as a CDK4/6 inhibitor. In high risk EBC, Verzenio has shown a persistent and deepening benefit beyond the two-year treatment period in the monarchE trial, the only adjuvant study designed specifically to investigate a CDK4/6 inhibitor in a high risk population.4 In metastatic breast cancer, Verzenio has demonstrated statistically significant OS in the Phase 3 MONARCH 2 study.5 Verzenio has shown a consistent and generally manageable safety profile across clinical trials. In addition to breast cancer, Lilly is studying Verzenio in different forms of difficult-to-treat prostate cancer.
Verzenio is an oral tablet taken twice daily and available in strengths of 50 mg, 100 mg, 150 mg, and 200 mg. Discovered and developed by Lilly researchers, Verzenio was first approved in 2017 and is currently authorized for use in more than 90 counties around the world. For full details on indicated uses of Verzenio in HR+, HER2- breast cancer, please see full Prescribing Information, available at www.Verzenio.com.
INDICATIONS FOR VERZENIO®VERZENIO® is a kinase inhibitor indicated:
IMPORTANT SAFETY INFORMATION FOR VERZENIO (abemaciclib)Severe diarrhea associated with dehydration and infection occurred in patients treated with Verzenio. Across four clinical trials in 3691 patients, diarrhea occurred in 81 to 90% of patients who received Verzenio. Grade 3 diarrhea occurred in 8 to 20% of patients receiving Verzenio. Most patients experienced diarrhea during the first month of Verzenio treatment. The median time to onset of the first diarrhea event ranged from 6 to 8 days; and the median duration of Grade 2 and Grade 3 diarrhea ranged from 6 to 11 days and 5 to 8 days, respectively. Across trials, 19 to 26% of patients with diarrhea required a Verzenio dose interruption and 13 to 23% required a dose reduction.
Instruct patients to start antidiarrheal therapy, such as loperamide, at the first sign of loose stools, increase oral fluids, and notify their healthcare provider for further instructions and appropriate follow-up. For Grade 3 or 4 diarrhea, or diarrhea that requires hospitalization, discontinue Verzenio until toxicity resolves to ≤Grade 1, and then resume Verzenio at the next lower dose.
Neutropenia, including febrile neutropenia and fatal neutropenic sepsis, occurred in patients treated with Verzenio. Across four clinical trials in 3691 patients, neutropenia occurred in 37 to 46% of patients receiving Verzenio. A Grade ≥3 decrease in neutrophil count (based on laboratory findings) occurred in 19 to 32% of patients receiving Verzenio. Across trials, the median time to first episode of Grade ≥3 neutropenia ranged from 29 to 33 days, and the median duration of Grade ≥3 neutropenia ranged from 11 to 16 days. Febrile neutropenia has been reported in
