Tamoxifen Citrate

Long-Term Follow-Up Data Signal Promising Progression-Free Survival (PFS) for Selinexor in the Maintenance Setting with Median PFS of 28.4 Months in the TP53 Wild-Type and 39.5 Months in the Proficient Mismatched Repair Status (pMMR) TP53 Wild-Type Exploratory Subgroups Q-TWiST, an Important Metric Assessing Both Quality and Quantity of Clinical Benefit, Suggests Improvement with Selinexor versus Placebo, which is Critical in the Maintenance Setting Company Highlights Additional Presentations in Endometrial Cancer and Myelofibrosis at ASCO 2024 NEWTON, Mass., June 1, 2024 /PRNewswire/ -- Karyopharm Therapeutics Inc. (Nasdaq: KPTI), a commercial-stage pharmaceutical company pioneering novel cancer therapies, today announced the presentation of updated exploratory subgroup analyses from the SIENDO study (NCT03555422), in patients with advanced or recurrent TP53 wild-type endometrial cancer at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting. The data were presented in a special ASCO plenary series rapid abstract update session on June 1 at 12:30pm CT and simultaneously published in the Gynecologic Oncology Journal. The primary analysis of the Phase 3 SIENDO study of selinexor maintenance therapy in advanced or recurrent endometrial cancer showed improvements in median PFS for the intent-to-treat (ITT) population but were not clinically meaningful. However, an exploratory analysis of a pre-specified subgroup of patients with TP53 wild-type endometrial cancer showed a promising efficacy signal. In the exploratory subgroup analysis, 113 patients with TP53 wild-type advanced/recurrent endometrial cancer were randomized to receive selinexor (n=77) vs placebo (n=36) as maintenance therapy after 1L platinum-based chemotherapy. As of the April 1, 2024 data cut-off date, and a median duration of follow-up of 36.9 months, selinexor-treated patients had a median PFS of 28.4 months compared to 5.2 months for patients receiving placebo. In selinexor-treated patients with TP53 wild-type/pMMR and TP53 wild-type/dMMR endometrial cancer, median PFS was 39.5 months and 13.1 months compared to 4.9 months and 3.7 months in those treated with placebo, respectively. Although immature, preliminary overall survival (OS) in the TP53 wild-type subgroup was promising with a hazard ratio of 0.65; median OS for selinexor has not been reached. The updated analyses also highlighted findings from a quality-adjusted time without symptoms or toxicity analysis (Q-TWiST) used to assess quality and toxicity-adjusted PFS. The findings showed the restricted mean Q-TWiST for selinexor to be 26 months compared to 15 months for placebo, resulting in a difference of nearly 11 months. "The approximately 40 months median PFS observed with selinexor in patients whose tumors are both TP53 wild-type and pMMR, coupled with the robust QTWiST analysis, suggests that selinexor may be an optimal maintenance therapy in endometrial cancer," said Reshma Rangwala, MD, PhD, Chief Medical Officer and Head of Research at Karyopharm. "Our ongoing Phase 3 trial will definitively assess these benefits and may lead to a new standard of care in the novel subgroup of patients defined by TP53 wild-type status." No new safety signals were identified as of the data cut-off date of April 1, 2024. The most common treatment-emergent adverse events (TEAEs) in selinexor treated TP53 wild-type patients were nausea (90%), vomiting (60%) and diarrhea (45%), the majority of which were grades 1-2. The most common reported grade 3-4 TEAEs included neutropenia (20%), nausea (13%), and thrombocytopenia (10%). TEAEs leading to discontinuations were reported in 17% of patients. "It is exciting to see the emerging data around progression free survival, as well as an encouraging trend in overall survival and the Q-TWiST metric in the TP53 wild-type subgroup analysis from the SIENDO study," said Vicky Makker, MD, Gynecologic Oncologist, Memorial Sloan Kettering Cancer Center. "The long-term follow-up data further reinforce how selinexor could benefit patients with endometrial cancer, including patients with mismatch repair-proficient disease, and add to the growing body of evidence supporting the potential role of selinexor as a maintenance treatment option for patients whose options are limited." A copy of the presentation from the "ASCO Plenary Series: Rapid Abstract Updates" special session can be accessed under "Publications and Presentations" in the Investor section of the Company's website, . Selinexor is being evaluated in a global, Phase 3, randomized, double-blind study, EC-042 (XPORT-EC-042; NCT05611931), as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer. Karyopharm expects to report data from this trial in the first half of 2025. The following Karyopharm abstracts will also be presented at ASCO: About the EC-042 Study EC-042 (XPORT-EC-042; NCT05611931) is a global, Phase 3, randomized, double-blind study evaluating selinexor as a maintenance therapy following systemic therapy in patients with TP53 wild-type advanced or recurrent endometrial cancer. The EC-042 study was initiated in November 2022 and is expected to enroll up to 220 patients who will be randomized 1:1 to receive either a 60 mg, once-weekly, administration of oral selinexor or placebo until disease progression. The primary endpoint of the study is progression free survival (PFS), as assessed by an investigator, with overall survival as a key secondary endpoint. Further, in connection with the EC-042 Study, Karyopharm entered into a global collaboration with Foundation Medicine, Inc. to develop FoundationOne®CDx, a tissue-based comprehensive genomic profiling test to identify and enroll patients whose tumors are TP53 wild-type. About the SIENDO Study Karyopharm's evaluation of selinexor to treat patients with TP53 wild-type advanced or recurrent endometrial cancer is supported by data from an exploratory subgroup analysis from its ongoing SIENDO Study, a European Network of Gynaecological Oncological Trial Groups (ENGOT)-led trial in collaboration with the Gynecologic Oncology Group (GOG) Foundation, Inc. The SIENDO Study is a multicenter, randomized, double-blinded Phase 3 study evaluating the efficacy and safety of oral selinexor versus placebo as a front-line maintenance therapy in patients with advanced or recurrent endometrial cancer following at least one prior platinum-based combination chemotherapy treatment (NCT03555422). Participants in this study with advanced or recurrent disease who had a partial response or a complete response after at least 12 weeks of taxane-platinum combination chemotherapy were randomized in a 2:1 manner to receive either maintenance therapy of 80 mg of selinexor or placebo taken once per week, until disease progression. The primary endpoint in the study was PFS from time of randomization until death or disease progression as assessed by an investigator, with the goal of the study demonstrating a HR of 0.6. In the first quarter of 2022, Karyopharm presented top-line data from the SIENDO study, including preliminary exploratory subgroup analyses. Selinexor-treated patients had a median PFS of 5.7 months compared to 3.8 months for patients on placebo in the full trial population, which was not clinically meaningful. There were no new safety signals identified, and a discontinuation rate of 10.5% due to adverse events (AEs). The most common treatment-emergent AEs in the SIENDO study of any grade were: nausea (84%), vomiting (52%), constipation (37%) and thrombocytopenia (37%). The most common grade 3 treatment-emergent AEs were nausea (10%), neutropenia (9%), thrombocytopenia (7%) and asthenia (6%). About Endometrial Cancer Endometrial cancer is the most common cancer of the female reproductive organs in the U.S., with approximately 67,880 new cases expected in 2024 leading to nearly 13,250 deaths.1 In 2022, there were approximately 124,874 new cases and 30,272 deaths in Europe from endometrial cancer, while on a global scale there were 420,368 new cases and approximately 97,723 deaths.2 Since 2000, the incidence of new cases and deaths from endometrial cancer have risen.3 Risk factors include obesity, Type 2 diabetes, high-fat diets, use of tamoxifen and oral estrogens, and delayed menopause.4 About XPOVIO® (selinexor) XPOVIO is a first-in-class, oral exportin 1 (XPO1) inhibitor and the first of Karyopharm's Selective Inhibitor of Nuclear Export (SINE) compounds approved for the treatment of cancer. XPOVIO functions by selectively binding to and inhibiting the nuclear export protein XPO1. XPOVIO is approved in the U.S. and marketed by Karyopharm in multiple oncology indications, including: (i) in combination with Velcade® (bortezomib) and dexamethasone (XVd) in adult patients with multiple myeloma who have received at least one prior therapy; (ii) in combination with dexamethasone in adult patients with relapsed or refractory multiple myeloma who have received at least four prior therapies and whose disease is refractory to at least two proteasome inhibitors, at least two immunomodulatory agents, and an anti-CD38 monoclonal antibody; and (iii) in adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), not otherwise specified, including DLBCL arising from follicular lymphoma, after at least two lines of systemic therapy. XPOVIO (also known as NEXPOVIO® in certain countries) has received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including but not limited to the European Union, the United Kingdom, China, South Korea, Canada, Israel and Taiwan. XPOVIO and NEXPOVIO is marketed by Karyopharm's partners, Antengene, Menarini, Neopharm and FORUS, in China, South Korea, Singapore, Australia, Hong Kong, Germany, Austria, Israel and Canada. Please refer to the local Prescribing Information for full details. Selinexor is also being investigated in several other mid- and late-stage clinical trials across multiple high unmet need cancer indications, including in endometrial cancer and myelofibrosis. For more information about Karyopharm's products or clinical trials, please contact the Medical Information department at: Tel: +1 (888) 209-9326 Email: [email protected] SELECT IMPORTANT SAFETY INFORMATION Warnings and Precautions Thrombocytopenia: Monitor platelet counts throughout treatment. Manage with dose interruption and/or reduction and supportive care. Neutropenia: Monitor neutrophil counts throughout treatment. Manage with dose interruption and/or reduction and granulocyte colony‐stimulating factors. Gastrointestinal Toxicity: Nausea, vomiting, diarrhea, anorexia, and weight loss may occur. Provide antiemetic prophylaxis. Manage with dose interruption and/or reduction, antiemetics, and supportive care. Hyponatremia: Monitor serum sodium levels throughout treatment. Correct for concurrent hyperglycemia and high serum paraprotein levels. Manage with dose interruption, reduction, or discontinuation, and supportive care. Serious Infection: Monitor for infection and treat promptly. Neurological Toxicity: Advise patients to refrain from driving and engaging in hazardous occupations or activities until neurological toxicity resolves. Optimize hydration status and concomitant medications to avoid dizziness or mental status changes. Embryo‐Fetal Toxicity: Can cause fetal harm. Advise females of reproductive potential and males with a female partner of reproductive potential, of the potential risk to a fetus and use of effective contraception. Cataract: Cataracts may develop or progress. Treatment of cataracts usually requires surgical removal of the cataract. Adverse Reactions The most common adverse reactions (≥20%) in patients with multiple myeloma who receive XVd are fatigue, nausea, decreased appetite, diarrhea, peripheral neuropathy, upper respiratory tract infection, decreased weight, cataract and vomiting. Grade 3‐4 laboratory abnormalities (≥10%) are thrombocytopenia, lymphopenia, hypophosphatemia, anemia, hyponatremia and neutropenia. In the BOSTON trial, fatal adverse reactions occurred in 6% of patients within 30 days of last treatment. Serious adverse reactions occurred in 52% of patients. Treatment discontinuation rate due to adverse reactions was 19%. The most common adverse reactions (≥20%) in patients with multiple myeloma who receive Xd are thrombocytopenia, fatigue, nausea, anemia, decreased appetite, decreased weight, diarrhea, vomiting, hyponatremia, neutropenia, leukopenia, constipation, dyspnea and upper respiratory tract infection. In the STORM trial, fatal adverse reactions occurred in 9% of patients. Serious adverse reactions occurred in 58% of patients. Treatment discontinuation rate due to adverse reactions was 27%. The most common adverse reactions (incidence ≥20%) in patients with DLBCL, excluding laboratory abnormalities, are fatigue, nausea, diarrhea, appetite decrease, weight decrease, constipation, vomiting, and pyrexia. Grade 3‐4 laboratory abnormalities (≥15%) are thrombocytopenia, lymphopenia, neutropenia, anemia, and hyponatremia. In the SADAL trial, fatal adverse reactions occurred in 3.7% of patients within 30 days, and 5% of patients within 60 days of last treatment; the most frequent fatal adverse reactions was infection (4.5% of patients). Serious adverse reactions occurred in 46% of patients; the most frequent serious adverse reaction was infection (21% of patients). Discontinuation due to adverse reactions occurred in 17% of patients. Use In Specific Populations Lactation: Advise not to breastfeed. For additional product information, including full prescribing information, please visit . To report SUSPECTED ADVERSE REACTIONS, contact Karyopharm Therapeutics Inc. at 1‐888‐209‐9326 or FDA at 1‐800‐FDA‐1088 or . About Karyopharm Therapeutics Karyopharm Therapeutics Inc. (Nasdaq: KPTI) is a commercial-stage pharmaceutical company whose dedication to pioneering novel cancer therapies is fueled by a belief in the extraordinary strength and courage of patients with cancer. Since its founding, Karyopharm has been an industry leader in oral compounds that address nuclear export dysregulation, a fundamental mechanism of oncogenesis. Karyopharm's lead compound and first-in-class, oral exportin 1 (XPO1) inhibitor, XPOVIO® (selinexor), is approved in the U.S. and marketed by the Company in three oncology indications. It has also received regulatory approvals in various indications in a growing number of ex-U.S. territories and countries, including Europe and the United Kingdom (as NEXPOVIO®) and China. Karyopharm has a focused pipeline targeting indications in multiple high unmet need cancers, including in multiple myeloma, endometrial cancer, myelofibrosis, and diffuse large B-cell lymphoma (DLBCL). For more information about our people, science and pipeline, please visit , and follow us on Twitter at @Karyopharm and LinkedIn. Forward-Looking Statements This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Such forward-looking statements include those regarding the ability of selinexor to treat patients with endometrial cancer; and expectations related to the clinical development of selinexor and potential regulatory submissions of selinexor. Such statements are subject to numerous important factors, risks and uncertainties, many of which are beyond Karyopharm's control, that may cause actual events or results to differ materially from Karyopharm's current expectations. For example, there can be no guarantee that Karyopharm will successfully commercialize XPOVIO or that any of Karyopharm's drug candidates, including selinexor and eltanexor, will successfully complete necessary clinical development phases or that development of any of Karyopharm's drug candidates will continue. Further, there can be no guarantee that any positive developments in the development or commercialization of Karyopharm's drug candidate portfolio will result in stock price appreciation. Management's expectations and, therefore, any forward-looking statements in this press release could also be affected by risks and uncertainties relating to a number of other factors, including the following: the adoption of XPOVIO in the commercial marketplace, the timing and costs involved in commercializing XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; the ability to obtain and retain regulatory approval of XPOVIO or any of Karyopharm's drug candidates that receive regulatory approval; Karyopharm's results of clinical trials and preclinical studies, including subsequent analysis of existing data and new data received from ongoing and future studies; the content and timing of decisions made by the U.S. Food and Drug Administration and other regulatory authorities, investigational review boards at clinical trial sites and publication review bodies, including with respect to the need for additional clinical studies; the ability of Karyopharm or its third party collaborators or successors in interest to fully perform their respective obligations under the applicable agreement and the potential future financial implications of such agreement; Karyopharm's ability to enroll patients in its clinical trials; unplanned cash requirements and expenditures; development or regulatory approval of drug candidates by Karyopharm's competitors for products or product candidates in which Karyopharm is currently commercializing or developing; the direct or indirect impact of the COVID-19 pandemic or any future pandemic on Karyopharm's business, results of operations and financial condition; and Karyopharm's ability to obtain, maintain and enforce patent and other intellectual property protection for any of its products or product candidates. These and other risks are described under the caption "Risk Factors" in Karyopharm's Quarterly Report on Form 10-Q for the quarter ended March 31, 2024, which was filed with the Securities and Exchange Commission (SEC) on May 8, 2024, and in other filings that Karyopharm may make with the SEC in the future. Any forward-looking statements contained in this press release speak only as of the date hereof, and, except as required by law, Karyopharm expressly disclaims any obligation to update any forward-looking statements, whether as a result of new information, future events or otherwise. XPOVIO® and NEXPOVIO® are registered trademarks of Karyopharm Therapeutics Inc. Any other trademarks referred to in this release are the property of their respective owners. References 1American Cancer Society, About Endometrial Cancer: (accessed May 22, 2024) 2International Agency for Research on Cancer, World Health Organization. "Top 15 Cancer Sites) (accessed May 22, 2024) 3Seer Cancer Incidence Rate Estimates, National Cancer Institute. Bethesda, MD. (accessed May 22, 2024) 4American Cancer Society, Endometrial Cancer Risk Factors. (accessed May 22, 2024) SOURCE Karyopharm Therapeutics Inc.

INDIANAPOLIS, May 23, 2024 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that data from studies of Verzenio® (abemaciclib; a CDK4/6 inhibitor), Retevmo® (selpercatinib; a rearranged during transfection [RET] inhibitor), olomorasib (an investigational KRAS G12C inhibitor) and imlunestrant (an investigational oral selective estrogen receptor degrader [SERD]) will be presented at the 2024 American Society of Clinical Oncology (ASCO) Annual Meeting taking place May 31 – June 4 in Chicago. Lilly will also host an investor event to provide an update on its oncology strategy and pipeline. The event will take place on Sunday, June 2, at 7:30 p.m. CDT and will be available via a live webcast on the "Webcasts & Presentations" section of Lilly's investor website. A replay will also be available on the website following the event. Presentation Highlights Verzenio (abemaciclib) In a late-breaking oral presentation, Lilly will report outcome data from the pivotal Phase 3 postMONARCH study evaluating Verzenio in combination with fulvestrant compared to placebo plus fulvestrant for patients with hormone receptor positive (HR+), human epidermal growth factor receptor 2 negative (HER2-) advanced or metastatic breast cancer with disease recurrence or progression on a prior CDK4/6i plus endocrine therapy. Retevmo (selpercatinib) In a rapid oral abstract presentation, Lilly will report results from the Phase 1/2 LIBRETTO-121 study evaluating the safety and efficacy of Retevmo in pediatric and adolescent patients with advanced solid tumors harboring an activating RET alteration. Olomorasib (investigational KRAS G12C inhibitor): In two oral presentations, Lilly will report updated results from the Phase 1/2 study evaluating the safety and efficacy of olomorasib (LY3537982), a potent and highly selective second-generation inhibitor of KRAS G12C, in combination with pembrolizumab in patients with KRAS G12C-mutant advanced non-small cell lung cancer (NSCLC), and updated results for olomorasib as a monotherapy in patients with KRAS G12C-mutant advanced solid tumors. Submitted abstracts utilized an October 30, 2023 data cut-off date, and the presentations will utilize a March 18, 2024 data cut-off date. A full list of abstract titles and viewing details are listed below: Verzenio (abemaciclib): Presentation Title: Abemaciclib plus fulvestrant vs fulvestrant alone for HR+, HER2- advanced breast cancer following progression on a prior CDK4/6 inhibitor plus endocrine therapy: Primary outcome of the phase 3 postMONARCH trial Abstract Number: LBA1001 Presentation Date & Time: Saturday, June 1, 3:00 p.m. – 3:12 p.m. CDT Location: Hall B1 (Live Stream) Presenter: Kevin Kalinsky Presentation Title: CYCLONE 2: A phase 3 study of abemaciclib with abiraterone in patients with metastatic castration-resistant prostate cancer Abstract Number: 5001 Presentation Date & Time: Saturday, June 1, 3:12 p.m. – 3:24 p.m. CDT Location: Arie Crown Theater (Live Stream) Presenter: Matthew Smith Presentation Title: Prognostic utility of ctDNA detection in the monarchE trial of adjuvant abemaciclib plus endocrine therapy (ET) in HR+, HER2-, node-positive, high-risk early breast cancer (EBC) Abstract Number: LBA507 Presentation Date & Time: Monday, June 3, 5:12 p.m. – 5:24 p.m. CDT Location: Hall B1 (Live Stream) Presenter: Sherene Loi Retevmo (selpercatinib) : Presentation Title: Safety and efficacy of selpercatinib in pediatric patients with RET-altered solid tumors: Updated results from LIBRETTO-121 Abstract Number: 10022 Presentation Date & Time: Sunday, June 2, 5:06 p.m. – 5:12 p.m. CDT Location: S504 (On Demand) Presenter: Daniel Morgenstern Presentation Title: Intracranial outcomes of 1L selpercatinib in advanced RET fusion-positive NSCLC: LIBRETTO-431 study Abstract Number: 8547 Presentation Date & Time: Monday, June 3, 1:30 p.m. – 4:30 p.m. CDT Location: Hall A (On Demand) Presenter: Maurice Perol Presentation Title: Selpercatinib in non-MTC, RET-mutated tumors: Efficacy in MEN-associated and other tumors Abstract Number: 3150 Presentation Date & Time: Saturday, June 1, 9:00 a.m. – 12:00 p.m. CDT Location: Hall A (On Demand) Presenter: Philippe Cassier Presentation Title: Health-related quality of life (HRQoL) and symptoms in LIBRETTO-431 patients with RET fusion-positive advanced non-small-cell lung cancer (NSCLC) Abstract Number: 11068 Presentation Date & Time: Monday, June 3, 9:00 a.m. – 12:00 p.m. CDT Location: Hall A (On Demand) Presenter: Caicun Zhou Presentation Title: Comparative patient-reported tolerability (PRT): A multiplicity-controlled analysis of LIBRETTO-531, a randomized controlled trial (RCT) in medullary thyroid cancer (MTC) Abstract Number: 11111 Presentation Date & Time: Monday, June 3, 9:00 a.m. – 12:00 p.m. CDT Location: Hall A (On Demand) Presenter: Marcia Brose Imlunestrant (investigational oral SERD): Presentation Title: Imlunestrant, an oral selective estrogen receptor degrader (SERD), in combination with human epidermal growth factor receptor 2 (HER2) directed therapy, with or without abemaciclib, in estrogen receptor (ER) positive, HER2 positive advanced breast cancer (aBC): EMBER phase 1a/1b study Abstract Number: 1027 Presentation Date & Time: Sunday, June 2, 9:00 a.m. – 12:00 p.m. CDT Location: Hall A (on Demand) Presenter: Manali Bhave Presentation Title: Imlunestrant, an oral selective estrogen receptor degrader (SERD), as monotherapy and in combination with abemaciclib, in endometrioid endometrial cancer (EEC): Results from the EMBER phase 1a/1b study Abstract Number: 5589 Presentation Date & Time: Monday, June 3, 9:00 a.m. – 12:00 p.m. CDT Location: Hall A (on Demand) Presenter: Kan Yonemori Olomorasib (investigational KRAS G12C inhibitor): Presentation Title: Efficacy and safety of olomorasib (LY3537982), a second-generation KRAS G12C inhibitor (G12Ci), in combination with pembrolizumab in patients with KRAS G12C-mutant advanced NSCLC Abstract Number: 8510 Presentation Date & Time: Saturday, June 1, 1:39 p.m. – 1:51 p.m. CDT Location: Hall B1 (Live Stream) Presenter: Timothy Burns Presentation Title: Pan-tumor activity of olomorasib (LY3537982), a second-generation KRAS G12C inhibitor (G12Ci), in patients with KRAS G12C-mutant advanced solid tumors Abstract Number: 3007 Presentation Date & Time: Saturday, June 1, 5:00 p.m. – 5:12 p.m. CDT Location: Hall D1 (Live Stream) Presenter: Rebecca Suk Heist 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. 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.1 NCCN® also includes Verzenio plus endocrine therapy as a preferred treatment option for metastatic breast cancer.2 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.2 In metastatic breast cancer, Verzenio has demonstrated statistically significant OS in the Phase 3 MONARCH 2 study.3 Verzenio has shown a consistent and generally manageable safety profile across clinical trials. 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 . INDICATIONS FOR VERZENIO® VERZENIO® is a kinase inhibitor indicated: in combination with endocrine therapy (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative, node-positive, early breast cancer at high risk of recurrence. in combination with an aromatase inhibitor as initial endocrine-based therapy for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer. in combination with fulvestrant for the treatment of adult patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer with disease progression following endocrine therapy. as monotherapy for the treatment of adult patients with HR-positive, HER2-negative advanced or metastatic breast cancer 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 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 diarrhea 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 <1% of patients exposed to Verzenio across trials. Two deaths due to neutropenic sepsis were observed in MONARCH 2. Inform patients to promptly report any episodes of fever to their healthcare provider. 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), 3% of patients experienced ILD or pneumonitis of any grade: 0.4% were Grade 3 or 4 and there was one fatality (0.1%). In Verzenio-treated patients in MBC (MONARCH 1, MONARCH 2, MONARCH 3), 3.3% of Verzenio-treated patients had ILD or pneumonitis of any grade: 0.6% had Grade 3 or 4, and 0.4% had fatal outcomes. Additional cases of ILD or pneumonitis have been observed in the postmarketing setting, with fatalities reported. 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 6%) and aspartate aminotransferase (AST) (2 to 3%) were reported in patients receiving Verzenio. Across three clinical trials in 3559 patients (monarchE, MONARCH 2, MONARCH 3), the median time to onset of Grade ≥3 ALT increases ranged from 57 to 87 days and the median time to resolution to Grade <3 was 13 to 14 days. The median time to onset of Grade ≥3 AST increases ranged from 71 to 185 days and the median time to resolution to Grade <3 ranged from 11 to 15 days. 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 5% of patients across three clinical trials in 3559 patients treated with Verzenio (monarchE, MONARCH 2, MONARCH 3). VTE included deep vein thrombosis, pulmonary embolism, pelvic venous thrombosis, cerebral venous sinus thrombosis, subclavian and axillary vein thrombosis, and inferior vena cava thrombosis. In clinical trials, deaths due to VTE have been reported in patients treated with Verzenio. 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, ≥10%) observed in monarchE for Verzenio plus tamoxifen or an aromatase inhibitor vs tamoxifen or an aromatase inhibitor, with a difference between arms of ≥2%, were diarrhea (84% vs 9%), infections (51% vs 39%), neutropenia (46% vs 6%), fatigue (41% vs 18%), leukopenia (38% vs 7%), nausea (30% vs 9%), anemia (24% vs 4%), headache (20% vs 15%), vomiting (18% vs 4.6%), stomatitis (14% vs 5%), lymphopenia (14% vs 3%), thrombocytopenia (13% vs 2%), decreased appetite (12% vs 2.4%), ALT increased (12% vs 6%), AST increased (12% vs 5%), dizziness (11% vs 7%), rash (11% vs 4.5%), and alopecia (11% vs 2.7 %). The most frequently reported ≥5% Grade 3 or 4 adverse reaction that occurred in the Verzenio arm vs the tamoxifen or an aromatase inhibitor arm of monarchE were neutropenia (19.6% vs 1%), leukopenia (11% vs <1%), diarrhea (8% vs 0.2%), and lymphopenia (5% vs <1%). Lab abnormalities (all grades; Grade 3 or 4) for monarchE in ≥10% for Verzenio plus tamoxifen or an aromatase inhibitor with a difference between arms of ≥2% were increased serum creatinine (99% vs 91%; .5% vs <.1%), decreased white blood cells (89% vs 28%; 19.1% vs 1.1%), decreased neutrophil count (84% vs 23%; 18.7% vs 1.9%), anemia (68% vs 17%; 1% vs .1%), decreased lymphocyte count (59% vs 24%; 13.2 % vs 2.5%), decreased platelet count (37% vs 10%; .9% vs .2%), increased ALT (37% vs 24%; 2.6% vs 1.2%), increased AST (31% vs 18%; 1.6% vs .9%), and hypokalemia (11% vs 3.8%; 1.3% vs 0.2%). The most common adverse reactions (all grades, ≥10%) observed in MONARCH 3 for Verzenio plus anastrozole or letrozole vs anastrozole or letrozole, with a difference between arms of ≥2%, were diarrhea (81% vs 30%), fatigue (40% vs 32%), neutropenia (41% vs 2%), infections (39% vs 29%), nausea (39% vs 20%), abdominal pain (29% vs 12%), vomiting (28% vs 12%), anemia (28% vs 5%), alopecia (27% vs 11%), decreased appetite (24% vs 9%), leukopenia (21% vs 2%), creatinine increased (19% vs 4%), constipation (16% vs 12%), ALT increased (16% vs 7%), AST increased (15% vs 7%), rash (14% vs 5%), pruritus (13% vs 9%), cough (13% vs 9%), dyspnea (12% vs 6%), dizziness (11% vs 9%), weight decreased (10% vs 3.1%), influenza-like illness (10% vs 8%), and thrombocytopenia (10% vs 2%). The most frequently reported ≥5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 3 were neutropenia (22% vs 1%), diarrhea (9% vs 1.2%), leukopenia (7% vs <1%)), increased ALT (6% vs 2%), and anemia (6% vs 1%). Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 3 in ≥10% for Verzenio plus anastrozole or letrozole with a difference between arms of ≥2% were increased serum creatinine (98% vs 84%; 2.2% vs 0%), decreased white blood cells (82% vs 27%; 13% vs 0.6%), anemia (82% vs 28%; 1.6% vs 0%), decreased neutrophil count (80% vs 21%; 21.9% vs 2.6%), decreased lymphocyte count (53% vs 26%; 7.6% vs 1.9%), decreased platelet count (36% vs 12%; 1.9% vs 0.6%), increased ALT (48% vs 25%; 6.6% vs 1.9%), and increased AST (37% vs 23%; 3.8% vs 0.6%). The most common adverse reactions (all grades, ≥10%) observed in MONARCH 2 for Verzenio plus fulvestrant vs fulvestrant, with a difference between arms of ≥2%, were diarrhea (86% vs 25%), neutropenia (46% vs 4%), fatigue (46% vs 32%), nausea (45% vs 23%), infections (43% vs 25%), abdominal pain (35% vs 16%), anemia (29% vs 4%), leukopenia (28% vs 2%), decreased appetite (27% vs 12%), vomiting (26% vs 10%), headache (20% vs 15%), dysgeusia (18% vs 2.7%), thrombocytopenia (16% vs 3%), alopecia (16% vs 1.8%), stomatitis (15% vs 10%), ALT increased (13% vs 5%), pruritus (13% vs 6%), cough (13% vs 11%), dizziness (12% vs 6%), AST increased (12% vs 7%), peripheral edema (12% vs 7%), creatinine increased (12% vs <1%), rash (11% vs 4.5%), pyrexia (11% vs 6%), and weight decreased (10% vs 2.2%). The most frequently reported ≥5% Grade 3 or 4 adverse reactions that occurred in the Verzenio arm vs the placebo arm of MONARCH 2 were neutropenia (25% vs 1%), diarrhea (13% vs 0.4%), leukopenia (9% vs 0%), anemia (7% vs 1%), and infections (5.7% vs 3.5%). Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 2 in ≥10% for Verzenio plus fulvestrant with a difference between arms of ≥2% were increased serum creatinine (98% vs 74%; 1.2% vs 0%), decreased white blood cells (90% vs 33%; 23.7% vs .9%), decreased neutrophil count (87% vs 30%; 32.5% vs 4.2%), anemia (84% vs 34%; 2.6% vs .5%), decreased lymphocyte count (63% vs 32%; 12.2% vs 1.8%), decreased platelet count (53% vs 15%; 2.1% vs 0%), increased ALT (41% vs 32%; 4.6% vs 1.4%), and increased AST (37% vs 25%; 3.9% vs 4.2%). The most common adverse reactions (all grades, ≥10%) observed in MONARCH 1 with Verzenio were diarrhea (90%), fatigue (65%), nausea (64%), decreased appetite (45%), abdominal pain (39%), neutropenia (37%), vomiting (35%), infections (31%), anemia (25%), thrombocytopenia (20%), headache (20%), cough (19%), constipation (17%), leukopenia (17%), arthralgia (15%), dry mouth (14%), weight decreased (14%), stomatitis (14%), creatinine increased (13%), alopecia (12%), dysgeusia (12%), pyrexia (11%), dizziness (11%), and dehydration (10%). The most frequently reported ≥5% Grade 3 or 4 adverse reactions from MONARCH 1 with Verzenio were diarrhea (20%), neutropenia (24%), fatigue (13%), and leukopenia (5%). Lab abnormalities (all grades; Grade 3 or 4) for MONARCH 1 with Verzenio were increased serum creatinine (99%; .8%), decreased white blood cells (91%; 28%), decreased neutrophil count (88%; 26.6%), anemia (69%; 0%), decreased lymphocyte count (42%; 13.8%), decreased platelet count (41%; 2.3%), increased ALT (31%; 3.1%), and increased AST (30%; 3.8%). 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). Please see full Prescribing Information and Patient Information for Verzenio. AL HCP ISI 12OCT2021 About Retevmo® (selpercatinib, 40 mg & 80 mg capsules) Retevmo (selpercatinib, formerly known as LOXO-292) (pronounced reh-TEHV-moh) is a highly selective and potent RET kinase inhibitor with central nervous system (CNS) activity. Retevmo may affect both tumor cells and healthy cells, which can result in side effects. RET-driver alterations are predominantly mutually exclusive from other oncogenic drivers. Retevmo is a U.S. FDA-approved oral prescription medicine, 120 mg or 160 mg dependent on weight (<50 kg or ≥50 kg, respectively), taken twice daily until disease progression or unacceptable toxicity.4 INDICATIONS FOR RETEVMO ® Retevmo® is kinase inhibitor indicated for the treatment of: Adult patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with a rearranged during transfection (RET) gene fusion, as detected by an FDA-approved test. Adult and pediatric patients 12 years of age and older with advanced or metastatic medullary thyroid cancer (MTC) with a RET mutation, as detected by an FDA-approved test, who require systemic therapy.1 Adult and pediatric patients 12 years of age and older with advanced or metastatic thyroid cancer with a RET gene fusion, as detected by an FDA-approved test, who require systemic therapy and who are radioactive iodine-refractory (if radioactive iodine is appropriate).1 Adult patients with locally advanced or metastatic solid tumors with a RET gene fusion that have progressed on or following prior systemic treatment or who have no satisfactory alternative treatment options.1 This indication is approved under accelerated approval based on overall response rate and duration of response. 1 Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trial(s). IMPORTANT SAFETY INFORMATION FOR RETEVMO® (selpercatinib) Hepatotoxicity: Serious hepatic adverse reactions occurred in 3% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 59% of patients, including Grade 3 or 4 events in 11% and increased alanine aminotransferase (ALT) occurred in 55% of patients, including Grade 3 or 4 events in 12%. Monitor ALT and AST prior to initiating Retevmo, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Severe, life-threatening, and fatal interstitial lung disease (ILD)/pneumonitis can occur in patients treated with Retevmo. ILD/pneumonitis occurred in 1.8% of patients who received Retevmo, including 0.3% with Grade 3 or 4 events, and 0.3% with fatal reactions. Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Retevmo and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose, or permanently discontinue Retevmo based on severity of confirmed ILD. Hypertension occurred in 41% of patients, including Grade 3 hypertension in 20% and Grade 4 in one (0.1%) patient. Overall, 6.3% had their dose interrupted and 1.3% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications. Do not initiate Retevmo in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Retevmo. Monitor blood pressure after 1 week, at least monthly thereafter, and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold, reduce dose, or permanently discontinue Retevmo based on the severity. Retevmo can cause concentration-dependent QT interval prolongation. An increase in QTcF interval to >500 ms was measured in 7% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 20% of patients. Retevmo has not been studied in patients with clinically significant active cardiovascular disease or recent myocardial infarction. Monitor patients who are at significant risk of developing QTc prolongation, including patients with known long QT syndromes, clinically significant bradyarrhythmias, and severe or uncontrolled heart failure. Assess QT interval, electrolytes, and thyroid-stimulating hormone (TSH) at baseline and periodically during treatment, adjusting frequency based upon risk factors including diarrhea. Correct hypokalemia, hypomagnesemia, and hypocalcemia prior to initiating Retevmo and during treatment. Monitor the QT interval more frequently when Retevmo is concomitantly administered with strong and moderate CYP3A inhibitors or drugs known to prolong QTc interval. Withhold and dose reduce or permanently discontinue Retevmo based on the severity. Serious, including fatal, hemorrhagic events can occur with Retevmo. Grade ≥3 hemorrhagic events occurred in 3.1% of patients treated with Retevmo including 4 (0.5%) patients with fatal hemorrhagic events, including cerebral hemorrhage (n=2), tracheostomy site hemorrhage (n=1), and hemoptysis (n=1). Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. Hypersensitivity occurred in 6% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.9%. The median time to onset was 1.9 weeks (range: 5 days to 2 years). Signs and symptoms of hypersensitivity included fever, rash and arthralgias or myalgias with concurrent decreased platelets or transaminitis. If hypersensitivity occurs, withhold Retevmo and begin corticosteroids at a dose of 1 mg/kg prednisone (or equivalent). Upon resolution of the event, resume Retevmo at a reduced dose and increase the dose of Retevmo by 1 dose level each week as tolerated until reaching the dose taken prior to onset of hypersensitivity. Continue steroids until patient reaches target dose and then taper. Permanently discontinue Retevmo for recurrent hypersensitivity. Tumor lysis syndrome (TLS) occurred in 0.6% of patients with medullary thyroid carcinoma receiving Retevmo. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated. Impaired wound healing can occur in patients who receive drugs that inhibit the vascular endothelial growth factor (VEGF) signaling pathway. Therefore, Retevmo has the potential to adversely affect wound healing. Withhold Retevmo for at least 7 days prior to elective surgery. Do not administer for at least 2 weeks following major surgery and until adequate wound healing. The safety of resumption of Retevmo after resolution of wound healing complications has not been established. Retevmo can cause hypothyroidism. Hypothyroidism occurred in 13% of patients treated with Retevmo; all reactions were Grade 1 or 2. Hypothyroidism occurred in 13% of patients (50/373) with thyroid cancer and 13% of patients (53/423) with other solid tumors including NSCLC. Monitor thyroid function before treatment with Retevmo and periodically during treatment. Treat with thyroid hormone replacement as clinically indicated. Withhold Retevmo until clinically stable or permanently discontinue Retevmo based on severity. Based on data from animal reproduction studies and its mechanism of action, Retevmo can cause fetal harm when administered to a pregnant woman. Administration of selpercatinib to pregnant rats during organogenesis at maternal exposures that were approximately equal to those observed at the recommended human dose of 160 mg twice daily resulted in embryolethality and malformations. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential and males with female partners of reproductive potential to use effective contraception during treatment with Retevmo and for 1 week after the last dose. There are no data on the presence of selpercatinib or its metabolites in human milk or on their effects on the breastfed child or on milk production. Because of the potential for serious adverse reactions in breastfed children, advise women not to breastfeed during treatment with Retevmo and for 1 week after the last dose. Severe adverse reactions (Grade 3-4) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001, were hypertension (20%), diarrhea (5%), prolonged QT interval (4.8%), dyspnea (3.1%), fatigue (3.1%), hemorrhage (2.6%), abdominal pain (2.5%), vomiting (1.8%), headache (1.4%), nausea (1.1%), constipation (0.8%), edema (0.8%), rash (0.6%), and arthralgia (0.3%). Serious adverse reactions occurred in 44% of patients who received Retevmo. The most frequently reported serious adverse reactions (in ≥2% of patients) were pneumonia, pleural effusion, abdominal pain, hemorrhage, hypersensitivity, dyspnea, and hyponatremia. Fatal adverse reactions occurred in 3% of patients; fatal adverse reactions included sepsis (n=6), respiratory failure (n=5), hemorrhage (n=4), pneumonia (n=3), pneumonitis (n=2), cardiac arrest (n=2), sudden death (n=1), and cardiac failure (n=1). Common adverse reactions (all grades) occurring in ≥20% of patients who received Retevmo in LIBRETTO-001, were edema (49%), diarrhea (47%), fatigue (46%), dry mouth (43%), hypertension (41%), abdominal pain (34%), rash (33%), constipation (33%), nausea (31%), headache (28%), cough (24%), vomiting (22%), dyspnea (22%), hemorrhage (22%), arthralgia (21%), and prolonged QT interval (21%). Laboratory abnormalities (all grades ≥20%; Grade 3-4) worsening from baseline in patients who received Retevmo in LIBRETTO-001, were increased AST (59%; 11%), decreased calcium (59%; 5.7%), increased ALT (56%; 12%), decreased albumin (56%; 2.3%), increased glucose (53%; 2.8%), decreased lymphocytes (52%; 20%), increased creatinine (47%; 2.4%), decreased sodium (42%; 11%), increased alkaline phosphatase (40%; 3.4%), decreased platelets (37%; 3.2%), increased total cholesterol (35%; 1.7%), increased potassium (34%; 2.7%), decreased glucose (34%; 1.0%), decreased magnesium (33%; 0.6%), increased bilirubin (30%; 2.8%), decreased hemoglobin (28%; 3.5%), and decreased neutrophils (25%; 3.2%). Concomitant use of acid-reducing agents decreases selpercatinib plasma concentrations which may reduce Retevmo antitumor activity. Avoid concomitant use of proton-pump inhibitors (PPIs), histamine-2 (H2) receptor antagonists, and locally-acting antacids with Retevmo. If coadministration cannot be avoided, take Retevmo with food (with a PPI) or modify its administration time (with a H2 receptor antagonist or a locally-acting antacid). Concomitant use of strong and moderate CYP3A inhibitors increases selpercatinib plasma concentrations which may increase the risk of Retevmo adverse reactions including QTc interval prolongation. Avoid concomitant use of strong and moderate CYP3A inhibitors with Retevmo. If concomitant use of a strong or moderate CYP3A inhibitor cannot be avoided, reduce the Retevmo dosage as recommended and monitor the QT interval with ECGs more frequently. Concomitant use of strong and moderate CYP3A inducers decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor activity. Avoid coadministration of Retevmo with strong and moderate CYP3A inducers. Concomitant use of Retevmo with CYP2C8 and CYP3A substrates increases their plasma concentrations which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with CYP2C8 and CYP3A substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for CYP2C8 and CYP3A substrates provided in their approved product labeling. Retevmo is a P-glycoprotein (P-gp) inhibitor. Concomitant use of Retevmo with P-gp substrates increases their plasma concentrations, which may increase the risk of adverse reactions related to these substrates. Avoid coadministration of Retevmo with P-gp substrates where minimal concentration changes may lead to increased adverse reactions. If coadministration cannot be avoided, follow recommendations for P-gp substrates provided in their approved product labeling. The safety and effectiveness of Retevmo have not been established in pediatric patients less than 12 years of age. The safety and effectiveness of Retevmo have been established in pediatric patients aged 12 years and older for medullary thyroid cancer (MTC) who require systemic therapy and for advanced RET fusion-positive thyroid cancer who require systemic therapy and are radioactive iodine-refractory (if radioactive iodine is appropriate). Use of Retevmo for these indications is supported by evidence from adequate and well-controlled studies in adults with additional pharmacokinetic and safety data in pediatric patients aged 12 years and older. Monitor open growth plates in adolescent patients. Consider interrupting or discontinuing Retevmo if abnormalities occur. No dosage modification is recommended for patients with mild to severe renal impairment (estimated Glomerular Filtration Rate [eGFR] ≥15 to 89 mL/min, estimated by Modification of Diet in Renal Disease [MDRD] equation). A recommended dosage has not been established for patients with end-stage renal disease. Reduce the dose when administering Retevmo to patients with severe hepatic impairment (total bilirubin greater than 3 to 10 times upper limit of normal [ULN] and any AST). No dosage modification is recommended for patients with mild or moderate hepatic impairment. Monitor for Retevmo-related adverse reactions in patients with hepatic impairment. Please see full Prescribing Information for Retevmo. SE HCP ISI All_21SEP22 About Imlunestrant Imlunestrant (LY3484356) is an investigational, next-generation oral selective estrogen receptor degrader (SERD) with pure antagonistic properties. The estrogen receptor (ER) is the key therapeutic target for patients with ER+/HER2- breast cancer. Novel degraders of ER may overcome endocrine therapy resistance while providing consistent oral pharmacology and convenience of administration. Imlunestrant was specifically designed to deliver continuous estrogen receptor target inhibition throughout the dosing period and regardless of ESR1 mutational status. Imlunestrant is currently being studied in several clinical trials. About Olomorasib Olomorasib (LY3537982) is an investigational, oral, potent, and highly selective second-generation inhibitor of the KRAS G12C protein. KRAS is the most common oncogene across all tumor types, and KRAS G12C mutations occur in 13% of patients with non-small cell lung cancer (NSCLC), and 1-3% of patients with other solid tumors.5 Olomorasib was specifically designed to target KRAS G12C mutations and has pharmacokinetic properties which allow for high predicted target occupancy and high potency when used as monotherapy or in combination.6 Olomorasib is currently being studied in the LOXO-RAS-20001 Phase 1/2 trial (NCT04956640) in patients with KRAS G12C-mutant NSCLC, and other advanced solid tumors and in the pivotal, registrational SUNRAY-01 global study (NCT06119581) investigating olomorasib in combination with pembrolizumab with or without chemotherapy for first-line treatment of KRAS G12C-mutant advanced NSCLC. For additional information about olomorasib clinical trials, please refer to clinicaltrials.gov. About Lilly Lilly is a medicine company turning science into healing to make life better for people around the world. We've been pioneering life-changing discoveries for nearly 150 years, and today our medicines help more than 51 million people across the globe. Harnessing the power of biotechnology, chemistry and genetic medicine, our scientists are urgently advancing new discoveries to solve some of the world's most significant health challenges: redefining diabetes care; treating obesity and curtailing its most devastating long-term effects; advancing the fight against Alzheimer's disease; providing solutions to some of the most debilitating immune system disorders; and transforming the most difficult-to-treat cancers into manageable diseases. With each step toward a healthier world, we're motivated by one thing: making life better for millions more people. That includes delivering innovative clinical trials that reflect the diversity of our world and working to ensure our medicines are accessible and affordable. To learn more, visit Lilly.com and Lilly.com/news, or follow us on Facebook, Instagram and LinkedIn. P-LLY Retevmo® is a registered trademark owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates. Verzenio® is a registered trademark owned or licensed by Eli Lilly and Company, its subsidiaries, or affiliates. © Lilly USA, LLC 2024. ALL RIGHTS RESERVED. Cautionary Statement Regarding Forward-Looking Statements This press release contains forward-looking statements (as that term is defined in the Private Securities Litigation Reform Act of 1995) about Verzenio® (abemaciclib) as a potential treatment for people with certain types of early breast cancer, Retevmo® (selpercatinib) as a potential treatment for people with locally advanced and metastatic RET fusion-positive NSCLC, RET-mutant MTC, and RET-activated thyroid cancer, imlunestrant as a potential treatment for people with certain types of breast cancer and olomorasib as a potential treatment for certain KRAS G12C-mutant advanced solid tumors, and reflects Lilly's current beliefs and expectations. However, as with any pharmaceutical product, there are substantial risks and uncertainties in the process of drug research, development, and commercialization. Among other things, there can be no guarantee that studies will be initiated or completed as planned, that future study results will be consistent with the results to date, or that Verzenio, Retevmo, imlunestrant, or olomorasib will receive initial regulatory approvals or approvals for additional indications, as applicable, or be commercially successful. For further discussion of these and other risks and uncertainties that could cause actual results to differ from Lilly's expectations, see Lilly's 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. 1 Referenced with permission from the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Breast Cancer V.2.2024. © National Comprehensive Cancer Network, Inc. 2024. All rights reserved. Accessed May 9, 2024. To view the most recent and complete version of the guidelines, go online to NCCN.org. NCCN makes no warranties of any kind whatsoever regarding their content, use or application and disclaims any responsibility for their application or use in any way. 2 Johnston SRD, Toi M, O'Shaughnessy J, Rastogi P, et al. Abemaciclib plus endocrine therapy for hormone receptor-positive, HER2-negative, node-positive, high-risk early breast cancer (monarchE): results from a preplanned interim analysis of a randomised, open-label, phase 3 trial. Lancet Oncol. 2023 Jan;24(1):77-90. 3 Sledge GW Jr, Toi M, Neven P, et al. The effect of abemaciclib plus fulvestrant on overall survival in hormone receptor-positive, ERBB2–negative breast cancer that progressed on endocrine therapy—MONARCH 2: a randomized clinical trial. JAMA Oncol. 2020;6(1):116-124. doi:10.1001/jamaoncol. 2019.4782. 4 Retevmo. Prescribing information. Lilly USA, LLC. 5 Ji J, Wang C, Fakih M. Targeting KRASG12C-mutated advanced colorectal cancer: Research and clinical developments. OncoTargets and Therapy. 2022;Volume 15:747-756. doi:10.2147/ott.s340392 6 Peng S-B, Si C, Zhang Y, et al. Abstract 1259: Preclinical characterization of Ly3537982, a novel, highly selective and potent KRAS-G12C inhibitor. Cancer Research. 2021;81(13_Supplement):1259-1259. doi:10.1158/1538-7445.am2021-1259 SOURCE Eli Lilly and Company