Lilly Announces Details of Presentations at 2022 American Association for Cancer Research (AACR)
Eli Lilly and Company (NYSE: LLY) will present data on pirtobrutinib and Verzenio at the 2022 American Association for Cancer Research (AACR) Annual Meeting from April 8-13, 2022. Key presentations include the BRUIN Phase 1b study results on pirtobrutinib for chronic lymphocytic leukemia and data on Verzenio’s efficacy against CDK4/6i resistance in breast cancer. These findings will enhance understanding of treatment options and potential outcomes for patients with relapsed conditions. Posters will be accessible on-demand until July 13, 2022.
- Presentation of promising data from the BRUIN Phase 1b study supports pirtobrutinib's potential in treating relapsed chronic lymphocytic leukemia.
- Research highlights Verzenio's ability to address resistance in breast cancer, showcasing its efficacy and expanding treatment options.
- None.
INDIANAPOLIS, March 8, 2022 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that data from the pirtobrutinib and Verzenio® (abemaciclib) development programs will be presented at the 2022 American Association for Cancer Research (AACR) Annual Meeting, April 8 - 13, 2022.
During the meeting, data will be presented from the BRUIN Phase 1b study of pirtobrutinib, an investigational, highly selective, non-covalent (reversible) BTK inhibitor, in combination with venetoclax with and without rituximab in relapsed/refractory chronic lymphocytic leukemia. Additionally, Lilly will present in vitro data on mechanistic insights into resistance to combination CDK4/6i plus endocrine therapy (ET) and the ability of Verzenio to overcome resistance when combined with ET for the treatment of palbociclib resistant breast cancer cell lines.
Details on poster presentations for pirtobrutinib and Verzenio are shared below:
Medicine | Abstract Title | Presentation Details |
Pirtobrutinib | Pirtobrutinib, a highly selective, non-covalent (reversible) BTK inhibitor in combination with venetoclax ± rituximab in relapsed/refractory chronic lymphocytic leukemia: Results from the BRUIN phase 1b study | Abstract #: CT138 Session: Phase I Clinical Trials 1 Session Date and Time: Monday, Apr 11, 2022 1:30 PM - 5:00 PM ET Location: Exhibit Halls D-H, Poster Section 35 |
Verzenio (abemaciclib) | Sequential treatment with abemaciclib + ET inhibits cell proliferation and triggers apoptosis in cell lines resistant to CDK4/6i | Abstract #: 2307 Session: Cell Cycle Control and Cell Cycle Regulators as Therapeutic Targets Session Date and Time: Tuesday, Apr 12, 2022 9:00 AM - 12:30 PM ET Location: Exhibit Halls D-H, Poster Section 5 Poster Board #: 11 |
Posters will be available on-demand on the AACR website at www.aacr.org beginning at the start of the poster session until July 13, 2022. The pirtobrutinib poster can also be viewed at www.loxooncology.com.
About Pirtobrutinib (LOXO-305)
Pirtobrutinib is an investigational, highly selective, non-covalent (reversible) Bruton's tyrosine kinase (BTK) inhibitor. BTK plays a key role in the B-cell antigen receptor signaling pathway, which is required for the development, activation and survival of normal white blood cells, known as B-cells, and malignant B-cells. BTK is a validated molecular target found across numerous B-cell leukemias and lymphomas including chronic lymphocytic leukemia, mantle cell lymphoma, Waldenström macroglobulinemia, and marginal zone lymphoma. Currently available covalent BTK inhibitors irreversibly inhibit BTK and the long-term efficacy of these therapies can be limited by acquired resistance, most commonly through BTK C481 mutations. In rapidly growing tumors with inherently high rates of BTK turnover, resistance to covalent BTK therapies may be the result of incomplete target inhibition. Pirtobrutinib was designed to reversibly bind BTK, deliver consistently high target coverage regardless of BTK turnover rate, preserve activity in the presence of the C481 acquired resistance mutations, and avoid off-target kinases that have complicated the development of both covalent and investigational non-covalent BTK inhibitors. Interested patients and physicians can contact the Loxo Oncology at Lilly Physician and Patient BTK Clinical Trial Hotline at 1-855-LOXO-305 or email clinicaltrials@loxooncology.com.
About the BRUIN Phase 1/2 Trial
This first-in-human, global, multi-center Phase 1/2 trial evaluates pirtobrutinib as a single agent in patients with previously treated chronic lymphocytic leukemia (CLL), small lymphocytic lymphoma (SLL), or non-Hodgkin's lymphomas (NHL). The trial includes a Phase 1 dose escalation phase and a Phase 2 dose expansion phase. The Phase 1 dose escalation enrolls patients with CLL/SLL or NHL who have received at least two prior lines of therapy and have progressed or are intolerant to standard of care. The primary objective of the Phase 1 portion of the trial is to determine the maximum tolerated dose and recommended Phase 2 dose. Key secondary objectives include measures of safety, pharmacokinetics, and anti-tumor activity (i.e. Overall Response Rate (ORR) and Duration of Response, as determined by appropriate histology-specific response criteria). In the Phase 2 dose expansion, patients are enrolled across various cohorts, depending on disease type and prior therapy. The primary endpoint for Phase 2 is ORR. Secondary endpoints include duration of response (DOR), overall survival (OS), safety, and pharmacokinetics (PK).
About Verzenio® (abemaciclib)
Verzenio® abemaciclib is a targeted treatment known as a CDK4/6 inhibitor. Verzenio is a non-chemotherapy oral tablet.
Verzenio works inside the cell to block CDK4/6 activity and help stop the growth of cancer cells, so they may eventually die (based on preclinical studies). Cyclin-dependent kinases (CDK)4/6 are activated by binding to D-cyclins. In estrogen receptor-positive (ER+) breast cancer cell lines, cyclin D1 and CDK4/6 promote phosphorylation of the retinoblastoma protein (Rb), cell cycle progression, and cell proliferation.
In vitro, continuous exposure to Verzenio inhibited Rb phosphorylation and blocked progression from G1 to S phase of the cell cycle, resulting in senescence and apoptosis (cell death). Preclinically, Verzenio dosed daily without interruption resulted in reduction of tumor size. Inhibiting CDK4/6 in healthy cells can result in side effects, some of which may be serious. Some CDK4/6 inhibitors require an intermittent dosing schedule (3 weeks on, 1 week off) due to bone marrow suppression. Verzenio is the only CDK4/6 inhibitor that is approved in the US with an continuous, twice daily dosing schedule. Clinical evidence also suggests that Verzenio crosses the blood-brain barrier. In patients with advanced cancer, including breast cancer, concentrations of Verzenio and its active metabolites (M2 and M20) in cerebrospinal fluid are comparable to unbound plasma concentrations.
INDICATIONS FOR VERZENIO
Verzenio® (abemaciclib) in combination with endocrine therapy (ET) is indicated for the adjuvant treatment of adult patients with hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), node-positive, early breast cancer (EBC) at high risk of recurrence and a Ki-67 score of ≥
Verzenio is indicated for the treatment of HR+ HER2- advanced or metastatic breast cancer:
- in combination with an aromatase inhibitor for postmenopausal women, and men, as initial endocrine-based therapy
- in combination with fulvestrant for adult patients with disease progression following endocrine therapy
- as a single agent for adult patients with disease progression following endocrine therapy and prior chemotherapy in the metastatic setting
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
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
Monitor complete blood counts prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, or delay in starting treatment cycles is recommended for patients who develop Grade 3 or 4 neutropenia.
Severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis can occur in patients treated with Verzenio and other CDK4/6 inhibitors. In Verzenio-treated patients in EBC (monarchE),
Monitor patients for pulmonary symptoms indicative of ILD or pneumonitis. Symptoms may include hypoxia, cough, dyspnea, or interstitial infiltrates on radiologic exams. Infectious, neoplastic, and other causes for such symptoms should be excluded by means of appropriate investigations. Dose interruption or dose reduction is recommended in patients who develop persistent or recurrent Grade 2 ILD or pneumonitis. Permanently discontinue Verzenio in all patients with Grade 3 or 4 ILD or pneumonitis.
Grade ≥3 increases in alanine aminotransferase (ALT) (2 to
Monitor liver function tests (LFTs) prior to the start of Verzenio therapy, every 2 weeks for the first 2 months, monthly for the next 2 months, and as clinically indicated. Dose interruption, dose reduction, dose discontinuation, or delay in starting treatment cycles is recommended for patients who develop persistent or recurrent Grade 2, or any Grade 3 or 4 hepatic transaminase elevation.
Venous thromboembolic events (VTE) were reported in 2 to
Verzenio has not been studied in patients with early breast cancer who had a history of VTE. Monitor patients for signs and symptoms of venous thrombosis and pulmonary embolism and treat as medically appropriate. Dose interruption is recommended for EBC patients with any grade VTE and for MBC patients with a Grade 3 or 4 VTE.
Verzenio can cause fetal harm when administered to a pregnant woman, based on findings from animal studies and the mechanism of action. In animal reproduction studies, administration of abemaciclib to pregnant rats during the period of organogenesis caused teratogenicity and decreased fetal weight at maternal exposures that were similar to the human clinical exposure based on area under the curve (AUC) at the maximum recommended human dose. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with Verzenio and for 3 weeks after the last dose. Based on findings in animals, Verzenio may impair fertility in males of reproductive potential. There are no data on the presence of Verzenio in human milk or its effects on the breastfed child or on milk production. Advise lactating women not to breastfeed during Verzenio treatment and for at least 3 weeks after the last dose because of the potential for serious adverse reactions in breastfed infants.
The most common adverse reactions (all grades, ≥
The most frequently reported ≥
Lab abnormalities (all grades; Grade 3 or 4) for monarchE in ≥
The most common adverse reactions (all grades, ≥
The most frequently reported ≥
Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 3 in ≥
The most common adverse reactions (all grades, ≥
The most frequently reported ≥
Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 2 in ≥
The most common adverse reactions (all grades, ≥
The most frequently reported ≥
Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 1 with Verzenio were increased serum creatinine (
Strong and moderate CYP3A inhibitors increased the exposure of abemaciclib plus its active metabolites to a clinically meaningful extent and may lead to increased toxicity. Avoid concomitant use of ketoconazole. Ketoconazole is predicted to increase the AUC of abemaciclib by up to 16-fold. In patients with recommended starting doses of 200 mg twice daily or 150 mg twice daily, reduce the Verzenio dose to 100 mg twice daily with concomitant use of strong CYP3A inhibitors other than ketoconazole. In patients who have had a dose reduction to 100 mg twice daily due to adverse reactions, further reduce the Verzenio dose to 50 mg twice daily with concomitant use of strong CYP3A inhibitors. If a patient taking Verzenio discontinues a strong CYP3A inhibitor, increase the Verzenio dose (after 3 to 5 half-lives of the inhibitor) to the dose that was used before starting the inhibitor. With concomitant use of moderate CYP3A inhibitors, monitor for adverse reactions and consider reducing the Verzenio dose in 50 mg decrements. Patients should avoid grapefruit products.
Avoid concomitant use of strong or moderate CYP3A inducers and consider alternative agents. Coadministration of strong or moderate CYP3A inducers decreased the plasma concentrations of abemaciclib plus its active metabolites and may lead to reduced activity.
With severe hepatic impairment (Child-Pugh C), reduce the Verzenio dosing frequency to once daily. The pharmacokinetics of Verzenio in patients with severe renal impairment (CLcr <30 mL/min), end stage renal disease, or in patients on dialysis is unknown. No dosage adjustments are necessary in patients with mild or moderate hepatic (Child-Pugh A or B) and/or renal impairment (CLcr ≥30-89 mL/min).
AL HCP ISI 12OCT2021
Please see full Prescribing Information for Verzenio.
About Lilly Oncology
For more than 50 years, Lilly has been dedicated to delivering life-changing medicines and support to people living with cancer and those who care for them. Lilly is determined to build on this heritage and continue making life better for all those affected by cancer around the world. To learn more about Lilly's commitment to people with cancer, please visit www.LillyOncology.com.
About Loxo Oncology at Lilly
Loxo Oncology at Lilly was created in December 2019, combining the Lilly Research Laboratories oncology organization and Loxo Oncology, which was acquired by Lilly in early 2019. Loxo Oncology at Lilly brings together the focus and spirit of a biotech with the scale and resources of large pharma, with the goal of rapidly delivering impactful new medicines for people with cancer. Our approach centers on creating new oncology medicines that unequivocally work early in clinical development and will matter to patients.
About Eli Lilly and Company
Lilly is a global health care leader that unites caring with discovery to create medicines that make life better for people around the world. We were founded more than a century ago by a man committed to creating high-quality medicines that meet real needs, and today we remain true to that mission in all our work. Across the globe, Lilly employees work to discover and bring life-changing medicines to those who need them, improve the understanding and management of disease, and give back to communities through philanthropy and volunteerism. To learn more about Lilly, please visit us at lilly.com and lilly.com/newsroom. P-LLY
Verzenio® is a trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates.
Lilly Forward-Looking Statement
This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Lilly's oncology portfolio and pipeline, including Verzenio and pirtobrutinib, and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of research, development, regulatory approval, and commercialization. Among other things, there can be no guarantee that future studies will be completed as planned, that future study results will be consistent with the results to date, that Verzenio or pirtobrutinib will receive (or receive additional) regulatory approvals or be commercially successful. For further discussion of these and other risks and uncertainties, see Lilly's most recent Form 10-K and Form 10-Q filings with the United States Securities and Exchange Commission. Except as required by law, Lilly undertakes no duty to update forward-looking statements to reflect events after the date of this release.
Refer to: | Lauren Cohen; lcohen@loxooncology.com; 617-678-2067 (Media) |
Kevin Hern; hern_kevin_r@lilly.com; 317-277-1838 (Investors) |
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