New LUMAKRAS® (sotorasib) Data From First Study Evaluating Intracranial Efficacy of a KRAS G12C Inhibitor Versus Docetaxel in Treated KRAS G12C-Mutated Advanced NSCLC
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
Novel Combinations Show Encouraging Safety and Efficacy in Pre-Treated KRAS G12C-Mutated Metastatic CRC and First-Line NSCLC
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
- Intracranial efficacy of sotorasib versus docetaxel in pretreated KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC): Practice-informing data from a global, Phase 3, randomized, controlled trial (RCT)
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
- Biomarker subgroup analyses of CodeBreaK 200, a Phase 3 trial of sotorasib versus docetaxel in patients (pts) with pretreated KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC)
Abstract #9008, Oral Abstract Session: Lung Cancer–Non-Small Cell Metastatic, Tuesday, June 6 from 9:45 a.m. – 12:45 p.m. CDT
- Sotorasib (Soto) plus panitumumab (Pmab) and FOLFIRI for previously treated KRAS G12C-mutated metastatic colorectal cancer (mCRC): CodeBreaK 101 Phase 1b safety and efficacy
Abstract #3513, Poster Session: Gastrointestinal Cancer—Colorectal and Anal,
Monday, June 5 from 8:00-11:00 a.m. CDT
- Matching-adjusted indirect treatment comparisons (MAIC) of sotorasib versus trifluridine/tipiracil (T/T) and regorafenib as monotherapy in chemorefractory KRAS G12C-mutated metastatic colorectal cancer (mCRC)
Abstract #3560, Poster Session: Gastrointestinal Cancer-Colorectal and Anal, Monday, June 5 from 8:00-11:00 a.m. CDT
- Real-world safety and effectiveness of MVASI in metastatic colorectal cancer patients in Canada
Abstract #e15555, Publication Only: Gastrointestinal Cancer—Colorectal and Anal
- Tarlatamab in small cell lung cancer (SCLC): Safety and efficacy analyzed by baseline brain metastasis
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
- Randomized Phase 3 study of tarlatamab, a DLL3-targeting bispecific T-cell engager (BiTE), compared to standard of care in patients with relapsed small cell lung cancer (DeLLphi-304)
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
- Prevalence of delta-like ligand 3 expression in small cell lung cancer
Abstract #e20618, Publication Only: Lung Cancer – Non-Small Cell Local-Regional/Small Cell/Other/Thoracic Cancers
- Long-term outcomes with isatuximab-carfilzomib-dexamethasone (Isa-Kd) in relapsed multiple myeloma patients with 1q21+ status: Updated results from the Phase 3 IKEMA study
Abstract #8029, Poster Session: Hematologic Malignancies—Plasma Cell Dyscrasia, Monday, June 5 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)
- Chemotherapy-free treatment with inotuzumab ozogamicin and blinatumomab for older adults with newly diagnosed, Philadelphia chromosome (Ph)-negative, CD22-positive, B-cell acute lymphoblastic leukemia: Alliance A041703
Abstract #7006, Oral Abstract Session: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant, Friday, June 2 from 1:00-4:00 p.m. CDT
- A Phase 2 study of hyper-CVAD with blinatumomab (blina) and inotuzumab ozogamicin (INO) for newly diagnosed Philadelphia chromosome (Ph)–negative B-cell acute lymphoblastic leukemia (ALL)
Abstract #e19017, Publication Only: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
- Mini-hyper-CVD plus inotuzumab ozogamicin (InO), with or without blinatumomab (blina), in older patients with newly diagnosed Philadelphia chromosome (Ph)-negative B-cell acute lymphoblastic leukemia (ALL): Updates from a Phase 2 trial
Abstract #e19025, Publication Only: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
- Phase 2 trial of mini-hyper-CVD-inotuzumab (InO) followed by blinatumomab (blina) consolidation in patients with relapsed/refractory (R/R) acute lymphoblastic leukemia (ALL)
Abstract #e19037, Publication Only: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
- A Phase 2 trial of ponatinib and blinatumomab in adults with newly diagnosed Philadelphia chromosome–positive acute lymphoblastic leukemia (Ph+ ALL)
Abstract #e19013, Publication Only: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
- Subgroup analysis from a Phase 2 trial of ponatinib and blinatumomab in relapsed/refractory (R/R) Philadelphia chromosome-positive acute lymphoblastic leukemia or chronic myeloid leukemia in lymphoid blast phase
Abstract #e19038, Publication Only: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
- Low-intensity chemotherapy (mini-HCVD) and ponatinib followed by blinatumomab (blina) and ponatinib for the treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL): A Phase 2 study
Abstract #e19028, Publication Only: Hematologic Malignancies—Leukemia, Myelodysplastic Syndromes, and Allotransplant
IMLYGIC® (talimogene laherparepvec)
- Neoadjuvant T-VEC + nivolumab combination therapy for resectable early metastatic (stage IIIB/C/D-IV M1a) melanoma with injectable disease: NIVEC trial
Abstract #9546, Poster Session: Melanoma/Skin Cancers, Saturday, June 3 from 1:15-4:15 p.m. CDT
- A Phase 2 study of talimogene laherparepvec (T-VEC) and pembrolizumab in patients with advanced sarcoma: Results of expansion cohorts
Abstract #11570, Poster Session: Sarcoma, Saturday, June 3 from 1:15-4:15 p.m. CDT
- Intralesional oncolytic virotherapy with talimogene laherparepvec in patients with cutaneous lymphomas and non-melanoma skin cancers
Abstract #9581, Poster Session: Melanoma/Skin Cancers, Saturday, June 3 from 1:15-4:15 p.m. CDT
- Phase 1b study of talimogene laherparepvec (T-VEC) in combination with chemotherapy (CT) or endocrine therapy (ET) in patients with metastatic, unresectable, or locoregionally recurrent HER2-negative breast cancer (BC)
Abstract #1091, Poster Session: Breast Cancer-Metastatic, Sunday, June 4 from 8:00-11:00 a.m. CDT
- Busulfan, melphalan, and carfilzomib (BuMelCar) conditioning for autologous stem cell transplant (ASCT) in multiple myeloma: Phase 1/2 data
Abstract #8021, Poster Session: Hematologic Malignancies—Plasma Cell Dyscrasia, Monday, June 5 from 8:00-11:00 a.m. CDT
- Carfilzomib, lenalidomide, and dexamethasone (KRd) versus elotuzumab and KRd in transplant-eligible patients with newly diagnosed multiple myeloma: Post-induction response and MRD results from an open-label randomized Phase 3 study
Abstract #8000, Oral Abstract Session: Hematologic Malignancies—Plasma Cell Dyscrasia, Saturday, June 3 from 1:15-4:15 p.m. CDT
- Maintenance therapy with carfilzomib, pomalidomide, and dexamethasone (KPd) in high-risk myeloma patients (pts): A Phase 2 study with a safety run-in
Abstract #8001, Oral Abstract Session: Hematologic Malignancies—Plasma Cell Dyscrasia, Saturday, June 3 from 1:15-4:15 p.m. CDT
- A Phase 1/2 study of carfilzomib, iberdomide (CC-220), and dexamethasone (KID) in patients with newly diagnosed transplant-eligible multiple myeloma
Abstract #e20043, Publication Only: Hematologic Malignancies—Plasma Cell Dyscrasia
- The primary endpoint analysis of SCARLET study: A single-arm, Phase 2 study of sotorasib plus carboplatin-pemetrexed in patients with advanced non-squamous, non-small cell lung cancer with KRAS G12C mutation (WJOG14821L)
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 Phase 2 study of sotorasib in participants (Pts) with previously treated stage IV or recurrent KRAS G12C mutant non-squamous (Non-sq) non-small cell lung cancer (NSCLC)
Abstract #TPS9143, Poster Session: Lung Cancer—Non-Small Cell Metastatic, Sunday, June 4 from 8:00-11:00 a.m. CDT
- Contemporary biomarker testing rates in both early and advanced NSCLC: Results from the MYLUNG pragmatic study
Abstract #9109, Poster Session: Lung Cancer—Non-Small Cell Metastatic, Sunday, June 4 from 8:00-11:00 a.m. CDT
- SPARK, studying pathways of resistance in KRAS-driven cancers: A remote plasma ctDNA participation study to identify mechanisms of resistance to KRAS inhibitors
Abstract #TPS3166, Poster Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology, Saturday, June 3 from 8:00-11:00 a.m. CDT
- Prevalence of KRAS p.G12C mutation in patients with metastatic non-small cell lung cancer in Argentina
Abstract #e21155, Publication Only: Lung Cancer—Non-Small Cell Metastatic
- Impact of number and size of colorectal metastases (CRM) on survival in patients with RAS wild-type metastatic colorectal cancer treated within the PanaMa trial (AIO KRK 0212)
Abstract #3551, Poster Session: Gastrointestinal Cancer—Colorectal and Anal, Monday, June 5 from 8:00-11:00 a.m. CDT
- Size-related heterogeneity of colorectal liver metastases (CRLM) in patients with advanced RAS wild-type metastatic colorectal cancer (mCRC) treated in the PanaMa trial: Implication for treatment decisions
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
- Denosumab for smoldering multiple myeloma: Rates of osteoporosis and change in lowest T-score after 12 months of treatment
Abstract #e20057, Publication Only: Hematologic Malignancies—Plasma Cell Dyscrasia
- CHARLI: A Phase 1b/2 trial of ipilimumab-nivolumab-denosumab or nivolumab-denosumab in patients with unresectable stage III and IV melanoma
Abstract #9525, Poster Session: Melanoma/Skin Cancers, Saturday, June 3 from 1:15-4:15 p.m. CDT
*Amgen out licenses Vectibix to Takeda in Japan.
About LUMAKRAS®/LUMYKRAS® (sotorasib)
Amgen took on one of the toughest challenges of the last 40 years in cancer research by developing LUMAKRAS/LUMYKRAS, a KRASG12C inhibitor.1 LUMAKRAS/LUMYKRAS has demonstrated a positive benefit-risk profile with rapid, deep, and durable anticancer activity in patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) harboring the KRAS G12C mutation with a once daily oral formulation.2
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.
LUMAKRAS/LUMYKRAS is also being studied in multiple other solid tumors.3
About 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.4 Overall survival rates for NSCLC are improving but remain poor for patients with advanced disease, and 5-year survival is only 9% for those with metastatic disease.5
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
About Advanced 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.9 It is also the third most commonly diagnosed cancer globally.10
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
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.13,14,15
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.
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
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
- 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, dose 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.
- 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 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.
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.
About Amgen Oncology
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 Otezla® (apremilast) (including anticipated Otezla 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.
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. A breakdown, cyberattack or information security breach 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
Michael Strapazon, 805-313-5553(media)
Jessica Akopyan, 805-440-5721 (media)
Arvind Sood, 805-447-1060 (investors)
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