Eli Lilly and Company (NYSE: LLY) today announced that data from programs across its oncology portfolio and pipeline will be presented at the 2021 American Association for Cancer Research (AACR) Annual Meeting, to be held virtually April 10-15, 2021
| INDIANAPOLIS, March 10, 2021 /PRNewswire/ -- Eli Lilly and Company (NYSE: LLY) today announced that data from programs across its oncology portfolio and pipeline will be presented at the 2021 American Association for Cancer Research (AACR) Annual Meeting, to be held virtually April 10-15, 2021. During the meeting, Lilly Oncology will present data from a study exploring safety and efficacy of its selective RET-kinase inhibitor Retevmo® (selpercatinib, 40 mg & 80 mg capsules) in patients with rearranged during transfection (RET) fusion-positive cancers outside of lung and thyroid cancer. Additionally, Loxo Oncology at Lilly, a research and development group of Eli Lilly and Company, will present preclinical characterization data for an oral selective estrogen receptor degrader (SERD), BCL2 inhibitor, next-generation KRAS-G12C inhibitor, and next-generation RET inhibitor. Portfolio Highlights Lilly will also present post-hoc efficacy data on Merck’s Phase 3 KEYNOTE-189 trial, which evaluated ALIMTA® (pemetrexed for injection) in combination with KEYTRUDA® (pembrolizumab) and cisplatin or carboplatin compared with ALIMTA in combination with placebo and cisplatin or carboplatin, in untreated patients with metastatic nonsquamous NSCLC, regardless of PD-L1 expression. Additionally, Lilly will present data on the Phase 3 ORIENT-3 trial, which evaluated sintilimab injection compared with docetaxel in patients with previously treated advanced/metastatic squamous NSCLC (sqNSCLC). Pipeline Highlights All posters will be available on-demand on the AACR website at www.aacr.org from April 10 – June 21. Loxo Oncology at Lilly posters can also be viewed at www.loxooncology.com. A list of the oral and poster presentations, along with viewing details, is highlighted below. Retevmo (selpercatinib) Presentation Title: Efficacy and Safety of Selpercatinib in RET Fusion-Positive Cancers Other than Lung or Thyroid Cancers Presentation Title: Safety of selpercatinib for RET-altered advanced solid tumors: a post hoc analysis of LIBRETTO-001 Alimta (pemetrexed) Presentation Title: Pemetrexed and Platinum plus Pembrolizumab in Patients with Metastatic Non-Squamous Non-Small Cell Lung Cancer By Tumor Burden at Baseline: A Post-hoc Efficacy Analysis of KEYNOTE-189 Sintilimab Presentation Title: ORIENT-3: A randomized, open-label, phase 3 study of sintilimab versus docetaxel in previously treated advanced/metastatic squamous non-small-cell lung cancer (sqNSCLC) Pipeline Presentation Title: Preclinical characterization of LY3484356, a novel, potent and orally bioavailable selective estrogen receptor degrader (SERD) Poster Title: Preclinical characterization of LOXO-338, a novel, oral and selective BCL2 inhibitor Presentation Title: Preclinical characterization of LY3537982, a novel, highly selective and potent KRAS-G12C inhibitor Poster Title: Preclinical characterization of potent and selective next-generation RET inhibitors About Retevmo® (selpercatinib) Retevmo (selpercatinib, formerly known as LOXO-292) (pronounced reh-TEHV-moh) is a selective and potent RET kinase inhibitor. 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 an 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.i Continued approval may be contingent upon verification and description of clinical benefit in confirmatory trials. About ALIMTA® (pemetrexed for injection) About Sintilimab In April 2020, the NMPA accepted the supplemental new drug application for sintilimab in combination with ALIMTA (pemetrexed for injection) and platinum as first-line therapy in advanced or recurrent non-squamous non-small cell lung cancer (NSCLC). In May 2020, sintilimab combined with gemcitabine and platinum chemotherapy met the predefined primary endpoint in the Phase 3 ORIENT-12 study as first-line therapy in patients with locally advanced or metastatic squamous NSCLC. Sintilimab monotherapy met the primary endpoint in the ORIENT-2 study as second-line therapy in patients with advanced or metastatic esophageal squamous cell carcinoma as well. In August 2020, the NMPA accepted the sNDA for sintilimab in combination with gemcitabine and platinum chemotherapy as first-line therapy in patients with locally advanced or metastatic squamous NSCLC. Sintilimab is a type of immunoglobulin G4 monoclonal antibody, which binds to PD-1 molecules on the surface of T-cells, blocks the PD-1/ PD-Ligand 1 (PD-L1) pathway and reactivates T-cells to kill cancer cells. Innovent is currently conducting more than 20 clinical studies with sintilimab to evaluate its safety and efficacy in a wide variety of cancer indications, including more than 10 registrational or pivotal clinical trials. Sintilimab injection is not an approved product in the United States. ALIMTA (pemetrexed for injection) is not approved for use in combination with sintilimab in the United States. IMPORTANT SAFETY INFORMATION FOR RETEVMO® (selpercatinib) Hepatotoxicity: Serious hepatic adverse reactions occurred in 2.6% of patients treated with Retevmo. Increased aspartate aminotransferase (AST) occurred in 51% of patients, including Grade 3 or 4 events in 8% and increased alanine aminotransferase (ALT) occurred in 45% of patients, including Grade 3 or 4 events in 9%. The median time to first onset for increased AST was 4.1 weeks (range: 5 days to 2 years) and increased ALT was 4.1 weeks (range: 6 days to 1.5 years). 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. Hypertension occurred in 35% of patients, including Grade 3 hypertension in 17% and Grade 4 in one (0.1%) patient. Overall, 4.6% 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 6% of patients and an increase in the QTcF interval of at least 60 ms over baseline was measured in 15% 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 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 2.3% of patients treated with Retevmo including 3 (0.4%) patients with fatal hemorrhagic events, including one case each of cerebral hemorrhage, tracheostomy site hemorrhage, and hemoptysis. Permanently discontinue Retevmo in patients with severe or life-threatening hemorrhage. Hypersensitivity occurred in 4.3% of patients receiving Retevmo, including Grade 3 hypersensitivity in 1.6%. The median time to onset was 1.7 weeks (range 6 days to 1.5 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 1% 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. 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 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 at least 1 week after the final 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 final dose. Severe adverse reactions (Grade 3-4) occurring in ≥15% of patients who received Retevmo in LIBRETTO-001, were hypertension (18%), prolonged QT interval (4%), diarrhea (3.4%), dyspnea (2.3%), fatigue (2%), abdominal pain (1.9%), hemorrhage (1.9%), headache (1.4%), rash (0.7%), constipation (0.6%), nausea (0.6%), vomiting (0.3%), and edema (0.3%). Serious adverse reactions occurred in 33% of patients who received Retevmo. The most frequently reported serious adverse reaction (in ≥ 2% of patients) was pneumonia. Fatal adverse reactions occurred in 3% of patients; fatal adverse reactions which occurred in >1 patient included sepsis (n=3), cardiac arrest (n=3) and respiratory failure (n=3). Common adverse reactions (all grades) occurring in ≥15% of patients who received Retevmo in LIBRETTO-001, were dry mouth (39%), diarrhea (37%), hypertension (35%), fatigue (35%), edema (35%), rash (27%), constipation (25%), nausea (23%), abdominal pain (23%), headache (23%), cough (18%), prolonged QT interval (17%), dyspnea (16%), vomiting (15%), and hemorrhage (15%). Laboratory abnormalities (all grades; Grade 3-4) ≥20% worsening from baseline in patients who received Retevmo in LIBRETTO-001, were AST increased (51%; 8%), ALT increased (45%; 9%), increased glucose (44%; 2.2%), decreased leukocytes (43%; 1.6%), decreased albumin (42%; 0.7%), decreased calcium (41%; 3.8%), increased creatinine (37%; 1.0%), increased alkaline phosphatase (36%; 2.3%), decreased platelets (33%; 2.7%), increased total cholesterol (31%; 0.1%), decreased sodium (27%; 7%), decreased magnesium (24%; 0.6%), increased potassium (24%; 1.2%), increased bilirubin (23%; 2.0%), and decreased glucose (22%; 0.7%). Concomitant use of acid-reducing agents decreases selpercatinib plasma concentrations which may reduce Retevmo anti-tumor 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. 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_05FEB2021 IMPORTANT SAFETY INFORMATION FOR ALIMTA® (pemetrexed for injection) CONTRAINDICATION
WARNINGS AND PRECAUTIONS
Renal Failure
Bullous and Exfoliative Skin Toxicity
Interstitial Pneumonitis
Radiation Recall
Increased Risk of Toxicity With Ibuprofen in Patients With Renal Impairment
Embryo-Fetal Toxicity
DRUG INTERACTIONS
ADVERSE REACTIONS
USE IN SPECIFIC PATIENT POPULATIONS
PM_HCP_ISI_NSCLC1L_Combo_30JAN2019 For safety and dosing guidelines for ALIMTA, see complete Warnings and Precautions, Adverse Reactions, and Dosage and Administration sections in the full Prescribing Information and Patient Prescribing Information. About Loxo Oncology at Lilly About Eli Lilly and Company © Lilly USA, LLC 2021. ALL RIGHTS RESERVED. ALIMTA® and Retevmo® are trademarks owned by or licensed to Eli Lilly and Company, its subsidiaries, or affiliates. Lilly 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 various therapies under development by Lilly and Loxo Oncology at Lilly, presentation of related data, and Lilly and Loxo Oncology’s strategy and pipeline, 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, 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 any of these therapies 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, 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. i RETEVMO [package insert]. Indianapolis, IN: Eli Lilly and Company; 2021.
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