Additional Analyses from DeLLphi-300 Highlight Safety and Clinical Efficacy of Tarlatamab, an Investigational First-in-Class BiTE® Immunotherapy, in Patients with SCLC With Treated and Stable Brain Metastases THOUSAND OAKS, Calif., June 1, 2023 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the presentation of new scientific and clinical research across its diverse oncology portfolio and pipeline at the American Society of Clinical Oncology (ASCO) Annual Meeting, taking place from June 2-6 in Chicago. More than 25 abstracts from Amgen-sponsored and collaborative studies, including three oral presentations and two poster discussions, will feature data in hard-to-treat tumor types, including non-small cell lung cancer (NSCLC), colorectal cancer (CRC) and small cell lung cancer (SCLC). "Our presentations at ASCO will illustrate how we're advancing novel approaches to address the toughest thoracic and colorectal cancers with limited treatment options," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "We're focused on expanding the reach and impact of our transformative, first-in-class medicines to help more people living with cancer." Additional information on Amgen abstracts is available on the ASCO website. Abstracts and Presentation Times:
Amgen Sponsored Abstracts Abstract #LBA9016, Poster Session: Lung Cancer–Non-Small Metastatic, Sunday, June 4 from 8:00-11:00 a.m. CDT. Poster Discussion Session: Lung Cancer–Non-Small Metastatic, Sunday, June 4 from 4:30-6:00 p.m. CDT Abstract #9008, Oral Abstract Session: Lung Cancer–Non-Small Cell Metastatic, Tuesday, June 6 from 9:45 a.m. – 12:45 p.m. CDT Monday, June 5 from 8:00-11:00 a.m. CDT
Abstract #3560, Poster Session: Gastrointestinal Cancer-Colorectal and Anal, Monday, June 5 from 8:00-11:00 a.m. CDT Abstract #8582, Poster Session: Lung Cancer-Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers, Sunday, June 4 from 8:00-11:00 a.m. CDT Abstract #TPS8611, Poster Session: Lung Cancer-Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers, Sunday, June 4 from 8:00-11:00 a.m. CDT Efficacy of panitumumab in patients with left-sided disease, MSS/MSI-L, and RAS/BRAF WT: A biomarker study of the Phase 3 PARADIGM trial Abstract #3508, Oral Abstract Session: Gastrointestinal Cancer—Colorectal and Anal, Sunday, June 4 from 8:00-11:00 a.m. CDT Investigator Sponsored Studies (ISS)
Neoadjuvant T-VEC + nivolumab combination therapy for resectable early metastatic (stage IIIB/C/D-IV M1a) melanoma with injectable disease: NIVEC trial Abstract #11570, Poster Session: Sarcoma, Saturday, June 3 from 1:15-4:15 p.m. CDT Abstract #1091, Poster Session: Breast Cancer-Metastatic, Sunday, June 4 from 8:00-11:00 a.m. CDT Abstract #9006, Oral Abstract Session: Lung Cancer—Non-Small Cell Metastatic, Tuesday, June 6 from 9:45 a.m. – 12:45 p.m. CDT ECOG-ACRIN LUNG-MAP S1900E substudy: A
Abstract #TPS9143, Poster Session: Lung Cancer—Non-Small Cell Metastatic, Sunday, June 4 from 8:00-11:00 a.m. CDT Abstract #9109, Poster Session: Lung Cancer—Non-Small Cell Metastatic, Sunday, June 4 from 8:00-11:00 a.m. CDT Abstract #TPS3166, Poster Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology, Saturday, June 3 from 8:00-11:00 a.m. CDT Abstract #e21155, Publication Only: Lung Cancer—Non-Small Cell Metastatic Abstract #3551, Poster Session: Gastrointestinal Cancer—Colorectal and Anal, Monday, June 5 from 8:00-11:00 a.m. CDT Abstract #3553, Poster Session: Gastrointestinal Cancer—Colorectal and Anal, Monday, June 5 from 8:00-11:00 a.m. CDT Intermittent or continuous panitumumab plus FOLFIRI (FOLFIRI/PANI) for first-line treatment of patients (pts) with RAS/BRAF wild-type (wt) metastatic colorectal cancer (mCRC): An update of survival/toxicity and preliminary results of genomic alterations from IMPROVE study Abstract #3571, Poster Session: Gastrointestinal Cancer—Colorectal and Anal, Monday, June 5 from 8:00-11:00 a.m. CDT Amgen is progressing the largest and broadest global KRASG12C inhibitor development program with unparalleled speed and exploring more than 10 sotorasib combination regimens, with clinical trial sites spanning five continents. To date, over 6,500 patients around the world have received LUMAKRAS/LUMYKRAS through the clinical development program and commercial use. In May 2021, LUMAKRAS was the first KRASG12C inhibitor to receive regulatory approval with its approval in the U.S., under accelerated approval. LUMAKRAS/LUMYKRAS is also approved in the European Union, Japan, United Arab Emirates, South Korea, Hong Kong, Switzerland, Taiwan, Qatar, and in Australia, Brazil, Canada, Great Britain, Singapore, and Israel under the FDA's Project Orbis. Additionally, Amgen has submitted MAAs in Argentina, Colombia, Kuwait, Macao, Malaysia, Mexico, Russia, Saudi Arabia, Thailand and Turkey. KRAS G12C is the most common KRAS mutation in NSCLC.6 About 13% of patients with NSCLC harbor the KRAS G12C mutation.7 Unmet medical need remains high and treatment options are limited for NSCLC patients with the KRAS G12C mutation whose first-line treatment has failed to work or has stopped working. The outcomes with other approved therapies are suboptimal, with a median progression-free survival of approximately four months following second-line treatment of KRAS G12C-mutated NSCLC.8 Patients with previously treated metastatic CRC need more effective treatment options. For patients in the third-line setting standard therapies yield median PFS times of about two months and patients' response rates are less than 2%.11,12 CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors.16 Eligible patients must have received a prior line of systemic anticancer therapy, consistent with their tumor type and stage of disease. The primary endpoint for the Phase 2 study was centrally assessed objective response rate. The Phase 2 trial in NSCLC enrolled 126 patients, 124 of whom had centrally evaluable lesions by RECIST at baseline.4 The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and results have been published.17 CodeBreaK 200, the global Phase 3 randomized active-controlled study comparing sotorasib to docetaxel in KRAS G12C-mutated NSCLC completed enrollment of 345 patients. Eligible patients had previously treated, locally advanced and unresectable or metastatic KRAS G12C-mutated NSCLC. The primary endpoint is progression-free survival and key secondary endpoints include overall survival, objective response rate, and patient-reported outcomes.18 Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment.19 A Phase 2 randomized study will evaluate sotorasib in patients with stage IV KRAS G12C-mutated NSCLC in need of first-line treatment (CodeBreaK 201).20 This indication is approved under accelerated approval based on overall response rate (ORR) and duration of response (DOR). Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).
Among 357 patients who received LUMAKRAS in CodeBreaK 100, hepatotoxicity occurred in 1.7% (all grades) and 1.4% (Grade 3). A total of 18% of patients who received LUMAKRAS had increased alanine aminotransferase (ALT)/increased aspartate aminotransferase (AST); 6% were Grade 3 and 0.6% were Grade 4. In addition to dose interruption or reduction, 5% of patients received corticosteroids for the treatment of hepatotoxicity. Monitor liver function tests (ALT, AST and total bilirubin) prior to the start of LUMAKRAS every 3 weeks for the first 3 months of treatment, then once a month or as clinically indicated, with more frequent testing in patients who develop transaminase and/or bilirubin elevations. Withhold, dose reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction. Most Common Adverse Reactions
Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
If coadministration with an acid-reducing agent cannot be avoided, inform patients to take LUMAKRAS 4 hours before or 10 hours after a locally acting antacid. Please see LUMAKRAS full Prescribing Information. Vectibix is the first and only fully human monoclonal anti-EGFR antibody approved by the FDA for the treatment of mCRC. Vectibix was approved in the U.S. in September 2006 as a monotherapy for the treatment of patients with EGFR-expressing mCRC after disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. In May 2014, the FDA approved Vectibix for use in combination with FOLFOX, as first-line treatment in patients with wild-type KRAS (exon 2) mCRC. With this approval, Vectibix became the first-and-only biologic therapy indicated for use with FOLFOX, one of the most commonly used chemotherapy regimens, in the first-line treatment of mCRC for patients with wild-type KRAS mCRC. In June 2017, the FDA approved a refined indication for Vectibix for use in in patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) mCRC. INDICATION AND LIMITATION OF USE
Vectibix® is indicated for the treatment of patients with wild-type RAS (defined as wild-type in both KRAS and NRAS as determined by an FDA-approved test for this use) metastatic colorectal cancer (mCRC): as first-line therapy in combination with FOLFOX, and as monotherapy following disease progression after prior treatment with fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy. Limitation of Use: Vectibix® is not indicated for the treatment of patients with RAS mutant mCRC or for whom RAS mutation status is unknown. IMPORTANT SAFETY INFORMATION
BOXED WARNING: DERMATOLOGIC TOXICITY
Dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients receiving Vectibix monotherapy [see Dosage and Administration (2.3), Warnings and Precautions (5.1), and Adverse Reactions (6.1)]. In Study 20020408, dermatologic toxicities occurred in 90% of patients and were severe (NCI-CTC grade 3 and higher) in 15% of patients with mCRC receiving Vectibix®. The clinical manifestations included, but were not limited to, acneiform dermatitis, pruritus, erythema, rash, skin exfoliation, paronychia, dry skin, and skin fissures. Monitor patients who develop dermatologic or soft tissue toxicities while receiving Vectibix® for the development of inflammatory or infectious sequelae. Life-threatening and fatal infectious complications including necrotizing fasciitis, abscesses, and sepsis have been observed in patients treated with Vectibix®. Life-threatening and fatal bullous mucocutaneous disease with blisters, erosions, and skin sloughing has also been observed in patients treated with Vectibix®. It could not be determined whether these mucocutaneous adverse reactions were directly related to EGFR inhibition or to idiosyncratic immune- related effects (e.g., Stevens Johnson syndrome or toxic epidermal necrolysis). Withhold or discontinue Vectibix® for dermatologic or soft tissue toxicity associated with severe or life-threatening inflammatory or infectious complications. Dose modifications for Vectibix® concerning dermatologic toxicity are provided in the product labeling. Vectibix® is not indicated for the treatment of patients with colorectal cancer that harbor somatic RAS mutations in exon 2 (codons 12 and 13), exon 3 (codons 59 and 61), and exon 4 (codons 117 and 146) of either KRAS or NRAS and hereafter is referred to as "RAS." Retrospective subset analyses across several randomized clinical trials were conducted to investigate the role of RAS mutations on the clinical effects of anti-EGFR-directed monoclonal antibodies (panitumumab or cetuximab). Anti-EGFR antibodies in patients with tumors containing RAS mutations resulted in exposing those patients to anti-EGFR related adverse reactions without clinical benefit from these agents. Additionally, in Study 20050203, 272 patients with RAS-mutant mCRC tumors received Vectibix® in combination with FOLFOX and 276 patients received FOLFOX alone. In an exploratory subgroup analysis, OS was shorter (HR = 1.21, 95% CI: 1.01-1.45) in patients with RAS-mutant mCRC who received Vectibix® and FOLFOX versus FOLFOX alone. Progressively decreasing serum magnesium levels leading to severe (grade 3-4) hypomagnesemia occurred in up to 7% (in Study 20080763) of patients across clinical trials. Monitor patients for hypomagnesemia and hypocalcemia prior to initiating Vectibix® treatment, periodically during Vectibix® treatment, and for up to 8 weeks after the completion of treatment. Other electrolyte disturbances, including hypokalemia, have also been observed. Replete magnesium and other electrolytes as appropriate. In Study 20020408, 4% of patients experienced infusion reactions and 1% of patients experienced severe infusion reactions (NCI-CTC grade 3-4). Infusion reactions, manifesting as fever, chills, dyspnea, bronchospasm, and hypotension, can occur following Vectibix® administration. Fatal infusion reactions occurred in postmarketing experience. Terminate the infusion for severe infusion reactions. Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix®. In an interim analysis of an open-label, multicenter, randomized clinical trial in the first-line setting in patients with mCRC, the addition of Vectibix® to the combination of bevacizumab and chemotherapy resulted in decreased OS and increased incidence of NCI-CTC grade 3-5 (87% vs 72%) adverse reactions. NCI-CTC grade 3-4 adverse reactions occurring at a higher rate in Vectibix®-treated patients included rash/acneiform dermatitis (26% vs 1%), diarrhea (23% vs 12%), dehydration (16% vs 5%), primarily occurring in patients with diarrhea, hypokalemia (10% vs 4%), stomatitis/mucositis (4% vs ®-treated patients (7% vs 3%) and included fatal events in three (®-treated patients. As a result of the toxicities experienced, patients randomized to Vectibix®, bevacizumab, and chemotherapy received a lower mean relative dose intensity of each chemotherapeutic agent (oxaliplatin, irinotecan, bolus 5-FU, and/or infusional 5-FU) over the first 24 weeks on study compared with those randomized to bevacizumab and chemotherapy. Vectibix® can cause fetal harm when administered to a pregnant woman. Advise pregnant women and females of reproductive potential of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment, and for at least 2 months after the last dose of Vectibix®. The most commonly reported adverse reactions (≥ 20%) with Vectibix® + FOLFOX were diarrhea, stomatitis, mucosal inflammation, asthenia, paronychia, anorexia, hypomagnesemia, hypokalemia, rash, acneiform dermatitis, pruritus, and dry skin. The most common serious adverse reactions (≥ 2% difference between treatment arms) were diarrhea and dehydration. To see the Vectibix® Prescribing Information, including Boxed Warning visit www.vectibix.com. Tarlatamab is an investigational, targeted immunotherapy engineered by Amgen researchers to engage a patient's own T cells to delta-like ligand 3 (DLL3) expressed on the surface of SCLC tumor cells.21,22 DLL3 represents an exciting therapeutic target for patients with SCLC, as approximately 85% of patients have expression of DLL3 on the cell surface of SCLC cells, with minimal expression in normal cells.23,24 In a Phase 1 study, tarlatamab demonstrated a manageable safety profile along with encouraging response durability in heavily pretreated patients with SCLC.21 Amgen is currently investigating tarlatamab in multiple trials, including DeLLphi-301, a potentially registrational Phase 2 study in heavily pretreated SCLC. The DeLLphi-304 trial is a Phase 3 study comparing tarlatamab with standard of care chemotherapy in second-line treatment of SCLC. At Amgen Oncology, our mission to serve patients drives all that we do. That's why we're relentlessly focused on accelerating the delivery of medicines that have the potential to empower all angles of care and transform lives of people with cancer. For the last four decades, we have been dedicated to discovering the firsts that matter in oncology and to finding ways to reduce the burden of cancer. Building on our heritage, Amgen continues to advance the largest pipeline in the Company's history, moving with great speed to advance those innovations for the patients who need them. For more information, follow us on www.twitter.com/amgenoncology.
Amgen is committed to unlocking the potential of biology for patients suffering from serious illnesses by discovering, developing, manufacturing and delivering innovative human therapeutics. This approach begins by using tools like advanced human genetics to unravel the complexities of disease and understand the fundamentals of human biology. Amgen focuses on areas of high unmet medical need and leverages its expertise to strive for solutions that improve health outcomes and dramatically improve people's lives. A biotechnology pioneer since 1980, Amgen has grown to be one of the world's leading independent biotechnology companies, has reached millions of patients around the world and is developing a pipeline of medicines with breakaway potential. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average and is also part of the Nasdaq-100 index. In 2022, Amgen was named one of the "World's Best Employers" by Forbes and one of "America's 100 Most Sustainable Companies" by Barron's. For more information, visit Amgen.com and follow us on Twitter, LinkedIn, Instagram, TikTok and YouTube. Amgen Forward-Looking Statements This news release contains forward-looking statements that are based on the current expectations and beliefs of Amgen. All statements, other than statements of historical fact, are statements that could be deemed forward-looking statements, including any statements on the outcome, benefits and synergies of collaborations, or potential collaborations, with any other company (including BeiGene, Ltd., Kyowa-Kirin Co., Ltd., or any collaboration to manufacture therapeutic antibodies against COVID-19), the performance of OtezlaOtezla® (apremilast) (including anticipated OtezlaOtezla sales growth and the timing of non-GAAP EPS accretion), the Five Prime Therapeutics, Inc. acquisition, the Teneobio, Inc. acquisition, the ChemoCentryx, Inc. acquisition, or the proposed acquisition of Horizon Therapeutics plc, as well as estimates of revenues, operating margins, capital expenditures, cash, other financial metrics, expected legal, arbitration, political, regulatory or clinical results or practices, customer and prescriber patterns or practices, reimbursement activities and outcomes, effects of pandemics or other widespread health problems such as the ongoing COVID-19 pandemic on our business, and other such estimates and results. Forward-looking statements involve significant risks and uncertainties, including those discussed below and more fully described in the Securities and Exchange Commission reports filed by Amgen, including our most recent annual report on Form 10-K and any subsequent periodic reports on Form 10-Q and current reports on Form 8-K. Unless otherwise noted, Amgen is providing this information as of the date of this news release and does not undertake any obligation to update any forward-looking statements contained in this document as a result of new information, future events or otherwise. No forward-looking statement can be guaranteed and actual results may differ materially from those we project. Discovery or identification of new product candidates or development of new indications for existing products cannot be guaranteed and movement from concept to product is uncertain; consequently, there can be no guarantee that any particular product candidate or development of a new indication for an existing product will be successful and become a commercial product. Further, preclinical results do not guarantee safe and effective performance of product candidates in humans. The complexity of the human body cannot be perfectly, or sometimes, even adequately modeled by computer or cell culture systems or animal models. The length of time that it takes for us to complete clinical trials and obtain regulatory approval for product marketing has in the past varied and we expect similar variability in the future. Even when clinical trials are successful, regulatory authorities may question the sufficiency for approval of the trial endpoints we have selected. We develop product candidates internally and through licensing collaborations, partnerships and joint ventures. Product candidates that are derived from relationships may be subject to disputes between the parties or may prove to be not as effective or as safe as we may have believed at the time of entering into such relationship. Also, we or others could identify safety, side effects or manufacturing problems with our products, including our devices, after they are on the market.
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Further, any scientific information discussed in this news release relating to new indications for our products is preliminary and investigative and is not part of the labeling approved by the U.S. Food and Drug Administration for the products. The products are not approved for the investigational use(s) discussed in this news release, and no conclusions can or should be drawn regarding the safety or effectiveness of the products for these uses. CONTACT: Amgen, Thousand Oaks Michael Strapazon, 805-313-5553(media)
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