Data From Newly FDA-Approved IMDELLTRA™ (tarlatamab-dlle) Further Reinforce Leadership in Bispecific T-Cell Engagers

Overall Survival Data from Phase 3 LUMAKRAS^® (sotorasib) Plus Vectibix^® (panitumumab) in Metastatic Colorectal Cancer Accepted as Late-Breaking Oral Presentation

THOUSAND OAKS, Calif., May 28, 2024 /PRNewswire/ -- Amgen (NASDAQ:AMGN) today announced the presentation of new data from its broad oncology portfolio at the American Society of Clinical Oncology (ASCO) 2024 Annual Meeting, taking place from May 31-June 4 in Chicago. The 17 abstracts from Amgen-sponsored and partner-led studies, including one late-breaking oral presentation, demonstrate Amgen's commitment to innovation and meaningfully improving outcomes for people living with difficult-to-treat cancers.

"At this year's ASCO, we're thrilled to present strong clinical research data with our medicines that target some of the most devastating cancers," said Jay Bradner, M.D., executive vice president, Research & Development, and chief scientific officer at Amgen. "Our focus is on molecular targets that we believe play a fundamental role in cancer progression, and by attacking these with our innovative combination therapies, we aim to bring real improvements in patient outcomes. Notably, we are advancing T-cell Engager therapies in both hematologic and solid tumors, and we are exploring LUMAKRAS plus Vectibix as a potentially practice-changing approach to metastatic colorectal cancer." 

Amgen sponsored studies with oral presentations include:

• Subgroup analysis of the Phase 2 DeLLphi-301 study demonstrated durable anticancer activity in relapsed/refractory small cell lung cancer (SCLC) regardless of the presence of treated, stable brain metastases at baseline. Analysis of intracranial activity will be presented.
• Research from a Phase 1b study (DeLLpro-300) showcasing IMDELLTRA safety results with encouraging anti-tumor activity in DLL3-expressing de novo or treatment-emergent neuroendocrine prostate cancer (NEPC).
• Data from the global, registration-enabling Phase 3 CodeBreaK 300 study, evaluating LUMAKRAS combined with Vectibix in chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC) was accepted as a late-breaking abstract and will report overall survival (OS) results.
• Updated analysis from the global Phase 1b CodeBreaK 101 study showing that LUMAKRAS plus chemotherapy had a positive benefit-risk profile, durable responses, and long-term control in patients who had or had not received prior treatment for KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC).

For more information on the Amgen abstracts, see below.

Abstracts and Presentation Times:

Amgen Sponsored Abstracts

LUMAKRAS^®/LUMYKRAS^® (sotorasib) for mCRC

• Overall survival (OS) of phase 3 CodeBreaK 300 study of sotorasib plus panitumumab (soto+pani) versus investigator's choice of therapy for KRAS G12C-mutated metastatic colorectal cancer (mCRC)
  Abstract #LBA3510, Rapid Oral Session: Gastrointestinal Cancer – Colorectal and Anal, Monday, June 3 from 1:15-2:45 p.m. CDT

IMDELLTRA^TM (tarlatamab-dlle)

• DeLLphi-301: Tarlatamab phase 2 trial in small cell lung cancer (SCLC)—Efficacy and safety analyzed by presence of brain metastasis
  Abstract #8015, Rapid Oral Session: Lung Cancer—Non-Small Cell Local-Regional/Small Cell/Other Thoracic Cancers, Sunday, June 2 from 4:30-6:00 p.m. CDT
• Phase 1b DeLLpro-300 study of Tarlatamab in de novo or treatment-emergent neuroendocrine prostate cancer (NEPC)
  Abstract #5012, Rapid Oral Session: Genitourinary Cancer—Prostate, Testicular, and Penile, Monday, June 3 from 1:15-2:45 p.m. CDT

LUMAKRAS^®/LUMYKRAS^® (sotorasib) for NSCLC

• Sotorasib plus carboplatin and pemetrexed in KRAS G12C advanced NSCLC: Updated analysis from the international CodeBreaK 101 trial
  Abstract #8512, Rapid Oral Session: Targeting KRAS in Non–Small Cell Lung Cancer, Saturday, June 1 from 1:15-2:45 p.m. CDT

Partner-Led Abstracts

Vectibix^® (panitumumab)

• Acquired gene alteration patterns and post-progression survival: PARADIGM study analysis
  Abstract #3507, Oral Session: Gastrointestinal Cancer—Colorectal and Anal, Sunday, June 2 from 8:00-11:00 a.m. CDT

Investigator Sponsored Studies (ISS)

BLINCYTO^® (blinatumomab)

• Comparison of immunoglobulin high-throughput sequencing MRD in bone marrow and peripheral blood in pediatric B-ALL: A report from the Children's Oncology Group AALL1731
  Abstract #10014, Oral Session: Pediatric Oncology II, Monday, June 3 from 11:30-2:30 p.m. CDT

Vectibix^® (panitumumab)

• FU/FA maintenance therapy with or without panitumumab (pmab) in RAS wild-type metastatic colorectal cancer (mCRC) (PanaMa, AIO KRK 0212): Updated efficacy analyses
  Abstract #3506, Oral Session: Gastrointestinal Cancer—Colorectal and Anal, Sunday, June 2 from 8:00-11:00 a.m. CDT

About IMDELLTRA™ (tarlatamab-dlle)
IMDELLTRA is a first-in-class immunotherapy engineered by Amgen researchers that binds to both DLL3 on tumor cells and CD3 on T cells, activating T cells to kill DLL3-expressing small cell lung cancer (SCLC) cells. This results in the formation of a cytolytic synapse with lysis of the cancer cell.^1,2 DLL3 is a protein that is expressed on the surface of SCLC cells in ~85-96% of patients with SCLC, but is minimally expressed on healthy cells, making it an exciting target.^3,4

About Small Cell Lung Cancer (SCLC)
Small cell lung cancer is one of the most aggressive and devastating solid tumor malignancies, with a median survival of approximately 12 months following initial therapy and a 3% five-year relative survival rate for extensive-stage SCLC.^5-7 Current second-line treatments impart a short duration of response (median DoR: 3.3–5.3 months) and limited survival (median OS: 5.8-9.3 months), while current third-line treatments for SCLC, which consist primarily of chemotherapy, yield a short median DoR of 2.6 months and a median OS of 4.4-5.3 months.^8-12 SCLC comprises ~15% of the 2.4 million plus patients diagnosed with lung cancer worldwide each year.^13-15 Despite initial high response rates to first-line platinum-based chemotherapy, most patients quickly relapse within months and require subsequent treatment options.¹³

IMDELLTRA™ (tarlatamab-dlle) U.S. Indication
IMDELLTRA™ (tarlatamab-dlle) is indicated for the treatment of adult patients with extensive-stage small cell lung cancer (ES-SCLC) with disease progression on or after platinum-based chemotherapy.

This indication is approved under accelerated approval based on overall response rate and duration of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

IMDELLTRA™ (tarlatamab-dlle) Important Safety Information

WARNING: CYTOKINE RELEASE SYNDROME AND NEUROLOGIC TOXICITY including IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME

• Cytokine release syndrome (CRS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRA^TM. Initiate treatment with IMDELLTRA^TM using the step-up dosing schedule to reduce the incidence and severity of CRS. Withhold IMDELLTRA^TM until CRS resolves or permanently discontinue based on severity.
• Neurologic toxicity, including immune effector cell-associated neurotoxicity syndrome (ICANS), including serious or life-threatening reactions, can occur in patients receiving IMDELLTRA^TM. Monitor patients for signs and symptoms of neurologic toxicity, including ICANS, during treatment and treat promptly. Withhold IMDELLTRA^TM until ICANS resolves or permanently discontinue based on severity.

WARNINGS AND PRECAUTIONS

• Cytokine Release Syndrome (CRS): IMDELLTRA^TM can cause CRS including serious or life-threatening reactions. In the pooled safety population, CRS occurred in 55% of patients who received IMDELLTRA^TM, including 34% Grade 1, 19% Grade 2, 1.1% Grade 3 and 0.5% Grade 4. Recurrent CRS occurred in 24% of patients, including 18% Grade 1 and 6% Grade 2.
  
  Most events (43%) of CRS occurred after the first dose, with 29% of patients experiencing any grade CRS after the second dose and 9% of patients experiencing CRS following the third dose or later. Following the Day 1, Day 8, and Day 15 infusions, 16%, 4.3% and 2.1% of patients experienced ≥ Grade 2 CRS, respectively. The median time to onset of all grade CRS from most recent dose of IMDELLTRA^TM was 13.5 hours (range: 1 to 268 hours). The median time to onset of ≥ Grade 2 CRS from most recent dose of IMDELLTRA^TM was 14.6 hours (range: 2 to 566 hours).
  
  Clinical signs and symptoms of CRS included pyrexia, hypotension, fatigue, tachycardia, headache, hypoxia, nausea, and vomiting. Potentially life-threatening complications of CRS may include cardiac dysfunction, acute respiratory distress syndrome, neurologic toxicity, renal and/or hepatic failure, and disseminated intravascular coagulation (DIC).
  
  Administer IMDELLTRA^TM following the recommended step-up dosing and administer concomitant medications before and after Cycle 1 IMDELLTRA^TM infusions as described in Table 3 of the Prescribing Information (PI) to reduce the risk of CRS. Administer IMDELLTRA^TM in an appropriate health care facility equipped to monitor and manage CRS. Ensure patients are well hydrated prior to administration of IMDELLTRA^TM.
  
  Closely monitor patients for signs and symptoms of CRS during treatment with IMDELLTRA^TM. At the first sign of CRS, immediately discontinue IMDELLTRA^TM infusion, evaluate the patient for hospitalization and institute supportive care based on severity. Withhold or permanently discontinue IMDELLTRA^TM based on severity. Counsel patients to seek medical attention should signs or symptoms of CRS occur.
  
  
• Neurologic Toxicity, Including ICANS: IMDELLTRA^TM can cause serious or life-threatening neurologic toxicity, including ICANS. In the pooled safety population, neurologic toxicity, including ICANS, occurred in 47% of patients who received IMDELLTRA^TM, including 10% Grade 3. The most frequent neurologic toxicities were headache (14%), peripheral neuropathy (7%), dizziness (7%), insomnia (6%), muscular weakness (3.7%), delirium (2.1%), syncope (1.6%), and neurotoxicity (1.1%).
  
  ICANS occurred in 9% of IMDELLTRA^TM-treated patients. Recurrent ICANS occurred in 1.6% of patients. Most patients experienced ICANS following Cycle 2 Day 1 (24%). Following Day 1, Day 8, and Day 15 infusions, 0.5%, 0.5% and 3.7% of patients experienced ≥ Grade 2 ICANS, respectively. The median time to onset of ICANS from the first dose of IMDELLTRA^TM was 29.5 days (range: 1 to 154 days). ICANS can occur several weeks following administration of IMDELLTRA^TM. The median time to resolution of ICANS was 33 days (range: 1 to 93 days).
  
  The onset of ICANS can be concurrent with CRS, following resolution of CRS, or in the absence of CRS. Clinical signs and symptoms of ICANS may include but are not limited to confusional state, depressed level of consciousness, disorientation, somnolence, lethargy, and bradyphrenia.
  
  Patients receiving IMDELLTRA^TM are at risk of neurologic adverse reactions and ICANS resulting in depressed level of consciousness. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, in the event of any neurologic symptoms until they resolve.
  
  Closely monitor patients for signs and symptoms of neurologic toxicity and ICANS during treatment. At the first sign of ICANS, immediately evaluate the patient and provide supportive therapy based on severity. Withhold IMDELLTRA^TM or permanently discontinue based on severity.
  
  
• Cytopenias: IMDELLTRA^TM can cause cytopenias including neutropenia, thrombocytopenia, and anemia. In the pooled safety population, decreased neutrophils occurred in 12% including 6% Grade 3 or 4 of IMDELLTRA^TM-treated patients. The median time to onset for Grade 3 or 4 neutropenia was 29.5 days (range: 2 to 213). Decreased platelets occurred in 33% including 3.2% Grade 3 or 4. The median time to onset for Grade 3 or 4 decreased platelets was 50 days (range: 3 to 420). Decreased hemoglobin occurred in 58% including 5% Grade 3 or 4. Febrile neutropenia occurred in 0.5% of patients treated with IMDELLTRA^TM.
  
  Monitor patients for signs and symptoms of cytopenias. Perform complete blood counts prior to treatment with IMDELLTRA^TM, before each dose, and as clinically indicated. Based on the severity of cytopenias, temporarily withhold, or permanently discontinue IMDELLTRA^TM.
  
  
• Infections: IMDELLTRA^TM can cause serious infections, including life-threatening and fatal infections. In the pooled safety population, infections, including opportunistic infections, occurred in 41% of patients who received IMDELLTRA^TM. Grade 3 or 4 infections occurred in 13% of patients. The most frequent infections were COVID-19 (9%, majority during the COVID-19 pandemic), urinary tract infection (10%), pneumonia (9%), respiratory tract infection (3.2%), and candida infection (3.2%).
  
  Monitor patients for signs and symptoms of infection prior to and during treatment with IMDELLTRA^TM and treat as clinically indicated. Withhold or permanently discontinue IMDELLTRA^TM based on severity.
  
  
• Hepatotoxicity: IMDELLTRA^TM can cause hepatotoxicity. In the pooled safety population, elevated ALT occurred in 42%, with Grade 3 or 4 ALT elevation occurring in 2.1%. Elevated AST occurred in 44% of patients, with Grade 3 or 4 AST elevation occurring in 3.2%. Elevated bilirubin occurred in 15% of patients; Grade 3 or 4 total bilirubin elevations occurred in 1.6% of patients. Liver enzyme elevation can occur with or without concurrent CRS. Monitor liver enzymes and bilirubin prior to treatment with IMDELLTRA^TM, before each dose, and as clinically indicated. Withhold IMDELLTRA^TM or permanently discontinue based on severity.
  
  
• Hypersensitivity: IMDELLTRA^TM can cause severe hypersensitivity reactions. Clinical signs and symptoms of hypersensitivity may include, but are not limited to, rash and bronchospasm. Monitor patients for signs and symptoms of hypersensitivity during treatment with IMDELLTRA^TM and manage as clinically indicated. Withhold or consider permanent discontinuation of IMDELLTRA^TM based on severity.
  
  
• Embryo-Fetal Toxicity: Based on its mechanism of action, IMDELLTRA^TM may cause fetal harm when administered to a pregnant woman. Advise patients of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with IMDELLTRA^TM and for 2 months after the last dose.

ADVERSE REACTIONS

• The most common (> 20%) adverse reactions were CRS (55%), fatigue (51%), pyrexia (36%), dysgeusia (36%), decreased appetite (34%), musculoskeletal pain (30%), constipation (30%), anemia (27%) and nausea (22%). The most common (≥ 2%) Grade 3 or 4 laboratory abnormalities were decreased lymphocytes (57%), decreased sodium (16%), increased uric acid (10%), decreased total neutrophils (6%), decreased hemoglobin (5%), increased activated partial thromboplastin time (5%), decreased potassium (5%), increased aspartate aminotransferase (3.2%), decreased white blood cells (3.8%), decreased platelets (3.2%), and increased alanine aminotransferase (2.1%).
• Serious adverse reactions occurred in 58% of patients. Serious adverse reactions in > 3% of patients included CRS (24%), pneumonia (6%), pyrexia (3.7%), and hyponatremia (3.6%). Fatal adverse reactions occurred in 2.7% of patients including pneumonia (0.5%), aspiration (0.5%), pulmonary embolism (0.5%), respiratory acidosis (0.5%), and respiratory failure (0.5%).

DOSAGE AND ADMINISTRATION: Important Dosing Information

• Administer IMDELLTRA^TM as an intravenous infusion over one hour.
• Administer IMDELLTRA^TM according to the step-up dosing schedule in the IMDELLTRA^TM PI (Table 1) to reduce the incidence and severity of CRS.
• For Cycle 1, administer recommended concomitant medications before and after Cycle 1 IMDELLTRA^TM infusions to reduce the risk of CRS reactions as described in the PI (Table 3).
• IMDELLTRA^TM should only be administered by a qualified healthcare professional with appropriate medical support to manage severe reactions such as CRS and neurologic toxicity including ICANS.
• Due to the risk of CRS and neurologic toxicity, including ICANS, monitor patients from the start of the IMDELLTRA^TM infusion for 22 to 24 hours on Cycle 1 Day 1 and Cycle 1 Day 8 in an appropriate healthcare setting.
• Recommend that patients remain within 1 hour of an appropriate healthcare setting for a total of 48 hours from start of the infusion with IMDELLTRA^TM following Cycle 1 Day 1 and Cycle 1 Day 8 doses, accompanied by a caregiver.
• Prior to administration of IMDELLTRA^TM evaluate complete blood count, liver enzymes, and bilirubin before each dose, and as clinically indicated.
• Ensure patients are well hydrated prior to administration of IMDELLTRA^TM.

Please see IMDELLTRA™ full Prescribing Information, including BOXED WARNINGS.

About LUMAKRAS^®/LUMYKRAS^® (sotorasib)
LUMAKRAS received accelerated approval from the U.S. Food and Drug Administration (FDA) on May 28, 2021. The U.S. FDA completed its review of Amgen's supplemental New Drug Application (sNDA) seeking full approval of LUMAKRAS^® on December 26, 2023, which resulted in a complete response letter. In addition, the FDA concluded that the dose comparison postmarketing requirement (PMR) issued at the time of LUMAKRAS accelerated approval, to compare the safety and efficacy of LUMAKRAS 960 mg daily dose versus a lower daily dose, has been fulfilled. The company said LUMAKRAS at 960 mg once-daily will remain the dose for patients with KRAS G12C-mutated NSCLC under accelerated approval. The U.S. FDA also issued a new PMR for an additional confirmatory study to support full approval that will be completed no later than February 2028.

About Metastatic Colorectal Cancer and the KRAS G12C Mutation
Colorectal cancer (CRC) is the second leading cause of cancer deaths worldwide, comprising 10% of all cancer diagnoses.¹⁶ It is also the third most commonly diagnosed cancer globally.¹⁷

Patients with previously treated metastatic CRC need more effective treatment options. For patients in the third-line setting, standard therapies yield median overall survival (OS) times of less than one year, and patients' response rates are less than 10%.¹⁸

KRAS mutations are among the most common genetic alterations in colorectal cancers, with the KRAS G12C mutation present in approximately 3-5% of colorectal cancers.^19-21 

About Advanced Non-Small Cell Lung Cancer and the KRAS G12C Mutation
Lung cancer is the leading cause of cancer-related deaths worldwide, and it accounts for more deaths worldwide than colon cancer, breast cancer and prostate cancer combined.²²

KRAS G12C is the most common KRAS mutation in NSCLC.²³ About 13% of patients with non-squamous NSCLC harbor the KRAS G12C mutation.²⁴ 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.

About CodeBreaK
The CodeBreaK clinical development program for Amgen's drug sotorasib is designed to study patients with an advanced solid tumor with the KRAS G12C mutation and address the longstanding unmet medical need for these cancers. 

Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment.²⁵ A Phase 2 randomized study evaluating sotorasib in patients with stage IV KRAS G12C-mutated NSCLC in need of first-line treatment is ongoing (CodeBreaK 201).²⁶ Amgen has also initiated a Phase 3 study of LUMAKRAS plus carboplatin and pemetrexed as front-line therapy in KRAS G12C-mutant, programmed death-ligand 1 (PD-L1) negative advanced NSCLC (CodeBreaK 202).

LUMAKRAS^® (sotorasib) U.S. Indication 
LUMAKRAS is indicated for the treatment of adult patients with KRAS G12C-mutated locally advanced or metastatic non-small cell lung cancer (NSCLC), as determined by an FDA-approved test, who have received at least one prior systemic therapy. 

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). 

LUMAKRAS^® (sotorasib) Important U.S. Safety Information 

Hepatotoxicity 

• LUMAKRAS can cause hepatotoxicity, which may lead to drug-induced liver injury and hepatitis.
• 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, reduce or permanently discontinue LUMAKRAS based on severity of adverse reaction.

Interstitial Lung Disease (ILD)/Pneumonitis 

• LUMAKRAS can cause ILD/pneumonitis that can be fatal. Among 357 patients who received LUMAKRAS in CodeBreaK 100, ILD/pneumonitis occurred in 0.8% of patients, all cases were Grade 3 or 4 at onset, and 1 case was fatal. LUMAKRAS was discontinued due to ILD/pneumonitis in 0.6% of patients.
• Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold LUMAKRAS in patients with suspected ILD/pneumonitis and permanently discontinue LUMAKRAS if no other potential causes of ILD/pneumonitis are identified.

Most Common Adverse Reactions 

• The most common adverse reactions occurring in ≥ 20% were diarrhea, musculoskeletal pain, nausea, fatigue, hepatotoxicity and cough.

Drug Interactions 

• Advise patients to inform their healthcare provider of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, dietary and herbal products.
• Inform patients to avoid proton pump inhibitors and H₂ receptor antagonists while taking LUMAKRAS.
• 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.  

About Vectibix^® (panitumumab)
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 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 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.
• Severe diarrhea and dehydration, leading to acute renal failure and other complications, have been observed in patients treated with Vectibix^® in combination with chemotherapy.
• Fatal and nonfatal cases of interstitial lung disease (ILD) (1%) and pulmonary fibrosis have been observed in patients treated with Vectibix^®. Pulmonary fibrosis occurred in less than 1% (2/1467) of patients enrolled in clinical studies of Vectibix^®. In the event of acute onset or worsening of pulmonary symptoms interrupt Vectibix^® therapy. Discontinue Vectibix^® therapy if ILD is confirmed.
• In patients with a history of interstitial pneumonitis or pulmonary fibrosis, or evidence of interstitial pneumonitis or pulmonary fibrosis, the benefits of therapy with Vectibix^® versus the risk of pulmonary complications must be carefully considered.
• Exposure to sunlight can exacerbate dermatologic toxicity. Advise patients to wear sunscreen and hats and limit sun exposure while receiving Vectibix^®.
• Keratitis and ulcerative keratitis, known risk factors for corneal perforation, have been reported with Vectibix^® use. Monitor for evidence of keratitis or ulcerative keratitis. Interrupt or discontinue Vectibix^® for acute or worsening keratitis.
• 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 < 1%), and hypomagnesemia (4% vs 0).
• NCI-CTC grade 3-5 pulmonary embolism occurred at a higher rate in Vectibix^®-treated patients (7% vs 3%) and included fatal events in three (< 1%) Vectibix^®-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^®.
• In monotherapy, the most commonly reported adverse reactions (≥ 20%) in patients with Vectibix^® were skin rash with variable presentations, paronychia, fatigue, nausea, and diarrhea.
• 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.

About BLINCYTO^® (blinatumomab)
BLINCYTO is the first globally approved BiTE^® immuno-oncology therapy that targets CD19 surface antigens on B cells. BiTE^® molecules fight cancer by helping the body's immune system detect and target malignant cells by engaging T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger cancer cell death (apoptosis). BiTE^® immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers.

BLINCYTO was granted breakthrough therapy and Priority Review designations by the U.S. FDA and is approved in the U.S. for the treatment of:

• CD19-positive B-ALL in first or second complete remission with MRD greater than or equal to 0.1% in adults and pediatric patients.
• Relapsed or refractory CD19-positive B-ALL in adults and pediatric patients.

In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:

• Adults with Philadelphia chromosome-negative CD19-positive relapsed or refractory B-ALL. Patients with Philadelphia chromosome-positive B-ALL should have failed treatment with at least two tyrosine kinase inhibitors (TKIs) and have no alternative treatment options.
• Adults with Philadelphia chromosome-negative CD19-positive B-ALL in first or second complete remission with MRD greater than or equal to 0.1%.
• Pediatric patients aged 1 year or older with Philadelphia chromosome-negative CD19-positive B-ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation.
• Pediatric patients aged 1 year or older with high-risk first relapsed Philadelphia chromosome-negative CD19-positive B-ALL as part of the consolidation therapy.

BLINCYTO^® IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

• Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO^®. Interrupt or discontinue BLINCYTO^® and treat with corticosteroids as recommended.
• Neurological toxicities, including immune effector cell-associated neurotoxicity syndrome (ICANS), which may be severe, life-threatening, or fatal, occurred in patients receiving BLINCYTO^®. Interrupt or discontinue BLINCYTO^® as recommended.

Contraindications
BLINCYTO^® is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

• Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in 15% of patients with R/R ALL and in 7% of patients with MRD-positive ALL. The median time to onset of CRS is 2 days after the start of infusion and the median time to resolution of CRS was 5 days among cases that resolved. Closely monitor and advise patients to contact their healthcare professional for signs and symptoms of serious adverse events such as fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO^® overlap with those of infusion reactions, capillary leak syndrome, and hemophagocytic histiocytosis/macrophage activation syndrome. If severe CRS occurs, interrupt BLINCYTO^® until CRS resolves. Discontinue BLINCYTO^® permanently if life-threatening CRS occurs. Administer corticosteroids for severe or life-threatening CRS.
• Neurological Toxicities: Approximately 65% of patients receiving BLINCYTO^® in clinical trials experienced neurological toxicities. The median time to the first event was within the first 2 weeks of BLINCYTO^® treatment and the majority of events resolved. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Severe, life–threatening, or fatal neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO^® as outlined in the PI.
• Infections: Approximately 25% of patients receiving BLINCYTO^® in clinical trials experienced serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO^® as needed.
• Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO^® treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO^® as needed to manage these events.
• Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO^® infusion and interrupt BLINCYTO^® if prolonged neutropenia occurs.
• Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO^® are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO^® is being administered.
• Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO^® treatment with a median time to onset of 3 days. In patients receiving BLINCYTO^®, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase, and TBILI prior to the start of and during BLINCYTO^® treatment. BLINCYTO^® treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.
• Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO^® in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO^® and dexamethasone as needed.
• Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO^®, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.
• Preparation and administration errors have occurred with BLINCYTO^® treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).
• Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO^® treatment, during treatment, and until immune recovery following last cycle of BLINCYTO^®.
• Benzyl Alcohol Toxicity in Neonates: Serious adverse reactions, including fatal reactions and the "gasping syndrome", have been reported in very low birth weight (VLBW) neonates born weighing less than 1500 g, and early preterm neonates (infants born less than 34 weeks gestational age) who received intravenous drugs containing benzyl alcohol as a preservative. Early preterm VLBW neonates may be more likely to develop these reactions, because they may be less able to metabolize benzyl alcohol.
  
  Use the preservative-free preparations of BLINCYTO^® where possible in neonates. When prescribing BLINCYTO^® (with preservative) for neonatal patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO^® (with preservative), other products containing benzyl alcohol or other excipients (e.g., ethanol, propylene glycol) which compete with benzyl alcohol for the same metabolic pathway.
  
  Monitor neonatal patients receiving BLINCYTO^® (with preservative) for new or worsening metabolic acidosis. The minimum amount of benzyl alcohol at which serious adverse reactions may occur in neonates is not known. The BLINCYTO^® 7-Day bag (with preservative) contains 7.4 mg of benzyl alcohol per mL.
• Embryo-Fetal Toxicity: Based on its mechanism of action, BLINCYTO^® may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with BLINCYTO^® and for 48 hours after the last dose.

Adverse Reactions

• The most common adverse reactions (≥ 20%) are pyrexia, infusion-related reactions, infections (pathogen unspecified), headache, neutropenia, anemia, and thrombocytopenia.

Dosage and Administration Guidelines

• BLINCYTO^® is administered as a continuous intravenous infusion at a constant flow rate using an infusion pump which should be programmable, lockable, non-elastomeric, and have an alarm.
• It is very important that the instructions for preparation (including admixing) and administration provided in the full Prescribing Information are strictly followed to minimize medication errors (including underdose and overdose).

INDICATIONS

• BLINCYTO^® (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adult and pediatric patients.
• BLINCYTO^® is indicated for the treatment of relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients.

Please see BLINCYTO^® full Prescribing Information, including BOXED WARNINGS.

About Bispecific T-Cell Engager (BiTE^®) Technology
BiTE technology is a targeted immuno-oncology platform that is designed to engage a patient's own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different cancer types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. For more than a decade, Amgen has been advancing this innovative technology, which has demonstrated strong efficacy in hematological malignancies and now a solid tumor with the approval of IMDELLTRA. Amgen remains committed to progressing multiple BiTE molecules across a broad range of hematologic and solid tumor malignancies, paving the way for additional applications in more tumor types.  Amgen is further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit BiTE^® Technology 101.

About Amgen 
Amgen discovers, develops, manufactures and delivers innovative medicines to help millions of patients in their fight against some of the world's toughest diseases. More than 40 years ago, Amgen helped to establish the biotechnology industry and remains on the cutting-edge of innovation, using technology and human genetic data to push beyond what's known today. Amgen is advancing a broad and deep pipeline that builds on its existing portfolio of medicines to treat cancer, heart disease, osteoporosis, inflammatory diseases and rare diseases.

In 2024, Amgen was named one of the "World's Most Innovative Companies" by Fast Company and one of "America's Best Large Employers" by Forbes, among other external recognitions. Amgen is one of the 30 companies that comprise the Dow Jones Industrial Average^®, and it is also part of the Nasdaq-100 Index^®, which includes the largest and most innovative non-financial companies listed on the Nasdaq Stock Market based on market capitalization.

For more information, visit Amgen.com and follow Amgen on X, LinkedIn, Instagram, TikTok, YouTube and Threads.

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. or Kyowa Kirin Co., Ltd.), the performance of Otezla^® (apremilast) (including anticipated Otezla sales growth and the timing of non-GAAP EPS accretion), our acquisitions of Teneobio, Inc., ChemoCentryx, Inc., or Horizon Therapeutics plc (including the prospective performance and outlook of Horizon's business, performance and opportunities, any potential strategic benefits, synergies or opportunities expected as a result of such acquisition, and any projected impacts from the Horizon acquisition on our acquisition-related expenses going forward), 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 on our business, outcomes, progress, 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.

Our results may be affected by our ability to successfully market both new and existing products domestically and internationally, clinical and regulatory developments involving current and future products, sales growth of recently launched products, competition from other products including biosimilars, difficulties or delays in manufacturing our products and global economic conditions. In addition, sales of our products are affected by pricing pressure, political and public scrutiny and reimbursement policies imposed by third-party payers, including governments, private insurance plans and managed care providers and may be affected by regulatory, clinical and guideline developments and domestic and international trends toward managed care and healthcare cost containment. Furthermore, our research, testing, pricing, marketing and other operations are subject to extensive regulation by domestic and foreign government regulatory authorities. Our business may be impacted by government investigations, litigation and product liability claims. In addition, our business may be impacted by the adoption of new tax legislation or exposure to additional tax liabilities. If we fail to meet the compliance obligations in the corporate integrity agreement between us and the U.S. government, we could become subject to significant sanctions. Further, while we routinely obtain patents for our products and technology, the protection offered by our patents and patent applications may be challenged, invalidated or circumvented by our competitors, or we may fail to prevail in present and future intellectual property litigation. We perform a substantial amount of our commercial manufacturing activities at a few key facilities, including in Puerto Rico, and also depend on third parties for a portion of our manufacturing activities, and limits on supply may constrain sales of certain of our current products and product candidate development. An outbreak of disease or similar public health threat, such as COVID-19, and the public and governmental effort to mitigate against the spread of such disease, could have a significant adverse effect on the supply of materials for our manufacturing activities, the distribution of our products, the commercialization of our product candidates, and our clinical trial operations, and any such events may have a material adverse effect on our product development, product sales, business and results of operations. We rely on collaborations with third parties for the development of some of our product candidates and for the commercialization and sales of some of our commercial products. In addition, we compete with other companies with respect to many of our marketed products as well as for the discovery and development of new products. Further, some raw materials, medical devices and component parts for our products are supplied by sole third-party suppliers. Certain of our distributors, customers and payers have substantial purchasing leverage in their dealings with us. The discovery of significant problems with a product similar to one of our products that implicate an entire class of products could have a material adverse effect on sales of the affected products and on our business and results of operations. Our efforts to collaborate with or acquire other companies, products or technology, and to integrate the operations of companies or to support the products or technology we have acquired, may not be successful. There can be no guarantee that we will be able to realize any of the strategic benefits, synergies or opportunities arising from the Horizon acquisition, and such benefits, synergies or opportunities may take longer to realize than expected. We may not be able to successfully integrate Horizon, and such integration may take longer, be more difficult or cost more than expected. A breakdown, cyberattack or information security breach of our information technology systems could compromise the confidentiality, integrity and availability of our systems and our data. Our stock price is volatile and may be affected by a number of events. Our business and operations may be negatively affected by the failure, or perceived failure, of achieving our environmental, social and governance objectives. The effects of global climate change and related natural disasters could negatively affect our business and operations. Global economic conditions may magnify certain risks that affect our business. Our business performance could affect or limit the ability of our Board of Directors to declare a dividend or our ability to pay a dividend or repurchase our common stock. We may not be able to access the capital and credit markets on terms that are favorable to us, or at all.

The scientific information discussed in this news release related to our product candidates is preliminary and investigative. Such product candidates are not approved by the U.S. Food and Drug Administration, and no conclusions can or should be drawn regarding the safety or effectiveness of the product candidates. 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
Elissa Snook, 609-251-1407 (media)
Justin Claeys, 805-313-9775 (investors) 

 

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