On May 26, 2022 Bristol Myers Squibb (NYSE: BMY) reported results from the primary analysis of PILOT, a multicenter, Phase 2 study evaluating Breyanzi (lisocabtagene maraleucel) in adults with refractory or relapsed large B-cell lymphoma (LBCL) after first-line therapy who were not deemed candidates for high-dose chemotherapy and hematopoietic stem cell transplant (HSCT) (Press release, Bristol-Myers Squibb, MAY 26, 2022, View Source [SID1234615072]). The PILOT study is the only company-sponsored trial to evaluate a CAR T cell therapy as a second-line treatment for patients with relapsed or refractory LBCL who are not considered candidates for stem cell transplant. The data will be presented in a poster presentation at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting on Saturday, June 4 from 9:00 AM – 12:00 PM EDT (ABSTRACT 7062).

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The PILOT study enrolled a broad patient population of adults with refractory or relapsed LBCL after first-line treatment who were not considered candidates for transplant based on age, performance status and/or organ function and comorbidities, and regardless of time to relapse following first-line treatment. With a median follow-up of 12.3 months, the majority of patients treated with Breyanzi (n=61) saw a reduction in disease, with 80% of patients responding to treatment (overall response rate; 95% CI: 68.2 – 89.4) and 54% of patients achieving a complete response (CR; 95% CI:40.8-66.9). Responses with Breyanzi were durable, with a median duration of response of 12.1 months (95% CI: 6.2-NR) at 15.5 months median follow-up. In patients who achieved a CR, median duration of response was 21.7 months (95% CI: 12.7-NR). Median progression-free survival with Breyanzi was 9.0 months (95% CI: 4.2-NR), and median overall survival has not been reached (95% CI: 17.3-NR). In the PILOT study, patients were treated with Breyanzi and monitoredin both the inpatient and outpatient setting.

"For patients with large B-cell lymphoma that is refractory to or relapses after first-line therapy, stem cell transplant has been the only potentially curative treatment option, but the reality is many patients are not candidates for stem cell transplant, leaving limited treatment options," said Leo I. Gordon, M.D., study investigator, Professor in Medicine, Northwestern University Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois. "The results from the PILOT study, including the patient-reported outcomes, show that treatment with liso-cel as a second-line therapy offers durable responses with improved quality of life for patients who historically have had poor prognosis."

LBCL, the most common type of non-Hodgkin lymphoma, is an aggressive blood cancer and approximately 40% of patients will have disease that is refractory to or relapses after first-line treatment. High-dose chemotherapy followed by autologous stem cell transplant has been the mainstay of care in the second-line setting; however, less than half of patients with primary refractory or relapsed disease are considered candidates for a stem cell transplant. For these patients, there are limited treatments that provide long-term disease control and palliative care is often the only option. If left untreated, patients with relapsed or refractory LBCL have a life expectancy of just three to four months.

"At Bristol Myers Squibb, we strive for cure by advancing innovative therapies that may provide long-term clinical benefit for some of the most challenging cancers with the hope of creating new standards of care that not only improve outcomes but also the patient experience," said Anne Kerber, senior vice president, Cell Therapy Development, Bristol Myers Squibb. "With Breyanzi, we have boldly designed a broad clinical trial program in relapsed or refractory LBCL, including patients who are not intended for stem cell transplant after failure of first-line therapy. These results from the PILOT study continue to demonstrate the practice-changing potential of Breyanzi in this setting, delivering on the promise of CAR T cell therapy for more patients."

In the PILOT study, Breyanzi showed a manageable safety profile with no new safety signals and low rates of severe cytokine release syndrome (CRS) or neurologic events, and no Grade 4/5 CRS or neurologic events reported. Any grade CRS occurred in 38% of patients, with Grade 3 CRS reported in one patient (2%). Any grade neurologic events were seen in 31% of patients with Grade 3 neurologic events reported in three patients (5%).

In a separate analysis of patient-reported outcomes (PRO) from the PILOT study, patients who received Breyanzi and were evaluable for the PRO analysis (n=56) showed significant improvements in fatigue and pain. Improvements in overall lymphoma symptoms were clinically meaningful following treatment with Breyanzi, and in an individual patient-level analysis, 70% of patients reported meaningful improvements in quality of life based on FACT-LymS scores at month 6. Results from the analysis will be presented in a poster presentation on Monday, June 6 from 2:15 PM – 5:15 PM EDT (Abstract 6567).

A supplemental Biologics License Application for Breyanzi for the treatment of relapsed or refractory LBCL after failure of first-line therapy is currently under Priority Review with the U.S. Food and Drug Administration (FDA), with an assigned Prescription Drug User Fee Act (PDUFA) goal date of June 24, 2022.

Breyanzi, a differentiated CD-19 directed CAR T cell therapy, is currently approved by the FDA for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Breyanzi is not indicated for the treatment of patients with primary central nervous system lymphoma.

About Breyanzi

Breyanzi is a CD-19 directed chimeric antigen receptor (CAR) T cell therapy, administered as a defined composition to reduce variability of the CD8 and CD4 component dose. Breyanzi has a 4-1BB costimulatory domain which enhances the expansion and persistence of the CAR T cells. Breyanzi was previously approved by the U.S. Food and Drug Administration for the treatment of adult patients with relapsed or refractory LBCL after two or more lines of systemic therapy, including diffuse large B-cell lymphoma (DLBCL) not otherwise specified (including DLBCL arising from indolent lymphoma), high-grade B-cell lymphoma, primary mediastinal large B-cell lymphoma, and follicular lymphoma grade 3B. Breyanzi is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.

Breyanzi is also approved in the European Union, Switzerland, Japan and Canada for relapsed and refractory LBCL after two or more lines of systemic therapy. Bristol Myers Squibb’s clinical development program for Breyanzi includes clinical studies in earlier lines of treatment for patients with relapsed or refractory LBCL and other types of lymphomas and leukemia. For more information, visit clinicaltrials.gov.

Breyanzi is not approved in any region for the second-line treatment of LBCL.

About PILOT

PILOT (NCT03483103) is a multicenter Phase 2 trial evaluating Breyanzi as a second-line therapy in adults with relapsed or refractory large B-cell lymphoma after first-line therapy who are ineligible for hematopoietic stem cell transplant (HSCT). All enrolled patients have relapsed or refractory large B-cell lymphoma after treatment with a single line of chemoimmunotherapy containing an anthracycline and a CD20-targeted agent and have been deemed non-candidates for high-dose chemotherapy and HSCT. The primary endpoint of the study is overall response rate. Other efficacy endpoints include complete response rate, duration of response, progression-free survival, event-free survival and overall survival.

Important Safety Information

BOXED WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGIC TOXICITIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients receiving BREYANZI. Do not administer BREYANZI to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab with or without corticosteroids.
Neurologic toxicities, including fatal or life-threatening reactions, occurred in patients receiving BREYANZI, including concurrently with CRS, after CRS resolution or in the absence of CRS. Monitor for neurologic events after treatment with BREYANZI. Provide supportive care and/or corticosteroids as needed.
BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS.
Cytokine Release Syndrome (CRS)

CRS, including fatal or life-threatening reactions, occurred following treatment with BREYANZI. CRS occurred in 46% (122/268) of patients receiving BREYANZI, including ≥ Grade 3 (Lee grading system) CRS in 4% (11/268) of patients. One patient had fatal CRS and 2 had ongoing CRS at time of death. The median time to onset was 5 days (range: 1 to 15 days). CRS resolved in 119 of 122 patients (98%) with a median duration of 5 days (range: 1 to 17 days). Median duration of CRS was 5 days (range 1 to 30 days) in all patients, including those who died or had CRS ongoing at time of death.

Among patients with CRS, the most common manifestations of CRS include fever (93%), hypotension (49%), tachycardia (39%), chills (28%), and hypoxia (21%). Serious events that may be associated with CRS include cardiac arrhythmias (including atrial fibrillation and ventricular tachycardia), cardiac arrest, cardiac failure, diffuse alveolar damage, renal insufficiency, capillary leak syndrome, hypotension, hypoxia, and hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS).

Ensure that 2 doses of tocilizumab are available prior to infusion of BREYANZI. Sixty-one of 268 (23%) patients received tocilizumab and/or a corticosteroid for CRS after infusion of BREYANZI. Twenty-seven (10%) patients received tocilizumab only, 25 (9%) received tocilizumab and a corticosteroid, and 9 (3%) received corticosteroids only.

Neurologic Toxicities

Neurologic toxicities that were fatal or life-threatening, occurred following treatment with BREYANZI. CAR T cell-associated neurologic toxicities occurred in 35% (95/268) of patients receiving BREYANZI, including ≥ Grade 3 in 12% (31/268) of patients. Three patients had fatal neurologic toxicity and 7 had ongoing neurologic toxicity at time of death. The median time to onset of the first event was 8 days (range: 1 to 46 days). The onset of all neurologic events occurred within the first 8 weeks following BREYANZI infusion. Neurologic toxicities resolved in 81 of 95 patients (85%) with a median duration of 12 days (range: 1 to 87 days). Three of four patients with ongoing neurologic toxicity at data cutoff had tremor and one subject had encephalopathy. Median duration of neurologic toxicity was 15 days (range: 1 to 785 days) in all patients, including those with ongoing neurologic events at the time of death or at data cutoff.

Seventy-eight (78) of 95 (82%) patients with neurologic toxicity experienced CRS. Neurologic toxicity overlapped with CRS in 57 patients. The onset of neurologic toxicity was after onset of CRS in 30 patients, before CRS onset in 13 patients, same day as CRS onset in 7 patients, and same day as CRS resolution in 7 patients.

Neurologic toxicity resolved in three patients before the onset of CRS. Eighteen patients experienced neurologic toxicity after resolution of CRS.

The most common neurologic toxicities included encephalopathy (24%), tremor (14%), aphasia (9%), delirium (7%), headache (7%), dizziness (6%), and ataxia (6%). Serious events including cerebral edema and seizures occurred with BREYANZI. Fatal and serious cases of leukoencephalopathy, some attributable to fludarabine, have occurred in patients treated with BREYANZI.

CRS and Neurologic Toxicities Monitoring

Monitor patients daily at a certified healthcare facility during the first week following infusion, for signs and symptoms of CRS and neurologic toxicities. Monitor patients for signs and symptoms of CRS and neurologic toxicities for at least 4 weeks after infusion; evaluate and treat promptly. Counsel patients to seek immediate medical attention should signs or symptoms of CRS or neurologic toxicity occur at any time. At the first sign of CRS, institute treatment with supportive care, tocilizumab or tocilizumab and corticosteroids as indicated.

BREYANZI REMS

Because of the risk of CRS and neurologic toxicities, BREYANZI is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the BREYANZI REMS. The required components of the BREYANZI REMS are:

Healthcare facilities that dispense and administer BREYANZI must be enrolled and comply with the REMS requirements.
Certified healthcare facilities must have on-site, immediate access to tocilizumab.
Ensure that a minimum of 2 doses of tocilizumab are available for each patient for infusion within 2 hours after BREYANZI infusion, if needed for treatment of CRS.
Certified healthcare facilities must ensure that healthcare providers who prescribe, dispense, or administer BREYANZI are trained on the management of CRS and neurologic toxicities.
Further information is available at www.BreyanziREMS.com, or contact Bristol Myers Squibb at 1-888-423-5436.

Hypersensitivity Reactions

Allergic reactions may occur with the infusion of BREYANZI. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO).

Serious Infections

Severe infections, including life-threatening or fatal infections, have occurred in patients after BREYANZI infusion. Infections (all grades) occurred in 45% (121/268) of patients. Grade 3 or higher infections occurred in 19% of patients. Grade 3 or higher infections with an unspecified pathogen occurred in 16% of patients, bacterial infections occurred in 5%, and viral and fungal infections occurred in 1.5% and 0.4% of patients, respectively. Monitor patients for signs and symptoms of infection before and after BREYANZI administration and treat appropriately. Administer prophylactic antimicrobials according to standard institutional guidelines.

Febrile neutropenia has been observed in 9% (24/268) of patients after BREYANZI infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad spectrum antibiotics, fluids, and other supportive care as medically indicated.

Avoid administration of BREYANZI in patients with clinically significant active systemic infections.

Viral reactivation: Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against B cells. Ten of the 11 patients in the TRANSCEND study with a prior history of HBV were treated with concurrent antiviral suppressive therapy to prevent HBV reactivation during and after treatment with BREYANZI. Perform screening for HBV, HCV, and HIV in accordance with clinical guidelines before collection of cells for manufacturing.

Prolonged Cytopenias

Patients may exhibit cytopenias not resolved for several weeks following lymphodepleting chemotherapy and BREYANZI infusion. Grade 3 or higher cytopenias persisted at Day 29 following BREYANZI infusion in 31% (84/268) of patients, and included thrombocytopenia (26%), neutropenia (14%), and anemia (3%). Monitor complete blood counts prior to and after BREYANZI administration.

Hypogammaglobulinemia

B-cell aplasia and hypogammaglobulinemia can occur in patients receiving treatment with BREYANZI. The adverse event of hypogammaglobulinemia was reported as an adverse reaction in 14% (37/268) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 21% (56/268) of patients. Hypogammaglobulinemia, either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion, was reported in 32% (85/268) of patients. Monitor immunoglobulin levels after treatment with BREYANZI and manage using infection precautions, antibiotic prophylaxis, and immunoglobulin replacement as clinically indicated.

Live vaccines: The safety of immunization with live viral vaccines during or following BREYANZI treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during BREYANZI treatment, and until immune recovery following treatment with BREYANZI.

Secondary Malignancies

Patients treated with BREYANZI may develop secondary malignancies. Monitor lifelong for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol Myers Squibb at 1-888-805-4555 for reporting and to obtain instructions on collection of patient samples for testing.

Effects on Ability to Drive and Use Machines

Due to the potential for neurologic events, including altered mental status or seizures, patients receiving BREYANZI are at risk for altered or decreased consciousness or impaired coordination in the 8 weeks following BREYANZI administration. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions

Serious adverse reactions occurred in 46% of patients. The most common nonlaboratory, serious adverse reactions (> 2%) were CRS, encephalopathy, sepsis, febrile neutropenia, aphasia, pneumonia, fever, hypotension, dizziness, and delirium. Fatal adverse reactions occurred in 4% of patients.

The most common nonlaboratory adverse reactions of any grade (≥ 20%) were fatigue, CRS, musculoskeletal pain, nausea, headache, encephalopathy, infections (pathogen unspecified), decreased appetite, diarrhea, hypotension, tachycardia, dizziness, cough, constipation, abdominal pain, vomiting, and edema.

Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.

Bristol Myers Squibb: Creating a Better Future for People with Cancer

Bristol Myers Squibb is inspired by a single vision—transforming patients’ lives through science. The goal of the company’s cancer research is to deliver medicines that offer each patient a better, healthier life and to make cure a possibility. Building on a legacy across a broad range of cancers that have changed survival expectations for many, Bristol Myers Squibb researchers are exploring new frontiers in personalized medicine, and through innovative digital platforms, are turning data into insights that sharpen their focus. Deep scientific expertise, cutting-edge capabilities and discovery platforms enable the company to look at cancer from every angle. Cancer can have a relentless grasp on many parts of a patient’s life, and Bristol Myers Squibb is committed to taking actions to address all aspects of care, from diagnosis to survivorship. Because as a leader in cancer care, Bristol Myers Squibb is working to empower all people with cancer to have a better future.

Learn more about the science behind cell therapy and ongoing research at Bristol Myers Squibb here.

On May 26, 2022 Bicycle Therapeutics plc (NASDAQ: BCYC), a biotechnology company pioneering a new and differentiated class of therapeutics based on its proprietary bicyclic peptide (Bicycle) technology, reported that the company will present a Trials in Progress poster highlighting the Phase I/II clinical trial of BT7480, a novel, fully synthetic Bicycle TICA targeting Nectin-4 and agonizing CD137, at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting taking place in Chicago, IL on June 3-7, 2022 (Press release, Bicycle Therapeutics, MAY 26, 2022, View Source [SID1234615071]).

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Poster Presentation Details

Title: A Combined Phase I/II Study of a Novel Bicycle Tumor-targeted Immune Cell Agonist BT7480 in Patients with Nectin-4 Associated Advanced Malignancies
Abstract #: TPS2689
Poster #: 332b
Presenter: Kyriakos P. Papadopoulos, START San Antonio
Session Title: Development Therapeutics – Immunotherapy
Date/Time: Sunday, June 5, 2022 at 9:00 a.m. ET

The poster will be available on the Publications section of bicycletherapeutics.com following the presentation.

On May 26, 2022 Arbutus Biopharma Corporation (Nasdaq: ABUS), a clinical-stage biopharmaceutical company leveraging its extensive virology expertise to develop novel therapeutics that target specific viral diseases, reported that its abstract on a preclinical oncology study for one of Arbutus’ oral PD-L1 inhibitor compounds designed to reawaken the immune system, has been selected for publication at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting being held June 3-7, 2022 (Press release, Arbutus Biopharma, MAY 26, 2022, View Source [SID1234615070]).

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Details for the abstract selected for publication are as follows:

Title: Pre-clinical anti-tumor activity of small-molecule oral PD-L1 checkpoint inhibitors

Abstract Number: e14558

Authors: Emily P Thi, Andrew G Cole, Gavin Heffernan, Christina L Iott, Seyma Ozturk, Sharie C Ganchua, Dan Nguyen, Ingrid Graves, Jorge G Quintero, Kim Stever, Kristi Fan, Vijay Ahuja, Steven G Kultgen, Maria Shubina, Boya Liu, Sunny Tang, Troy O Harasym, Angela M Lam and Michael J Sofia

Session: Publication Only – Journal of Clinical Oncology.

The abstract is available on ASCO (Free ASCO Whitepaper)’s website at //asco.org/abstracts.

About PD-L1

Immune checkpoints such as PD-1/PD-L1 play an important role in the induction and maintenance of immune tolerance and in T-cell activation. We have identified a class of small-molecule oral PD-L1 inhibitors that we believe will allow for controlled checkpoint blockade, enable oral dosing, and mitigate systemic safety issues typically seen with checkpoint antibody therapies.

On May 26, 2022 Aravive, Inc. (Nasdaq: ARAV, "the Company"), a late clinical-stage oncology company developing targeted therapeutics to treat metastatic disease, reported the presentation of updated Phase 1b/2 ccRCC data at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) annual meeting, taking place June 3-7, 2022 in Chicago (Press release, Aravive, MAY 26, 2022, View Source [SID1234615069]). The abstract presents the updated response rate, landmark progression-free-survival data, and biomarker data.

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"We are jubilant about the selection of the poster on the use of batiraxcept in 2L+ ccRCC for oral discussion at this year’s ASCO (Free ASCO Whitepaper) annual meeting," said Gail McIntyre, Ph.D., DABT, Chief Executive Officer of Aravive. "This is a rare opportunity provided only to select abstracts at this meeting. Batiraxcept continues to show best-in-class potential in advanced or metastatic clear cell renal carcinoma, platinum resistant ovarian cancer, and pancreatic cancer. Enrollment in the registration directed Phase 3 program in PROC remains on pace to complete this year and we look forward to providing updates on the renal and pancreatic cancer programs throughout 2022."

Abstract Title: A Phase 1b/2 study of batiraxcept (AVB-S6-500) in combination with cabozantinib in patients with advanced or metastatic clear cell renal cell carcinoma (ccRCC) who have received front-line treatment (NCT04300140)
Abstract Number: 4511 (Poster Discussion Session – Data will be presented)
Poster Session: Genitourinary Cancer—Kidney and Bladder
Session Date: Poster Presentation: Saturday, June 4, 2022, 1:15 PM – 4:15 PM CDT
Discussion: Saturday, June 4, 2022, 4:30 PM CDT (5:30 PM EDT)

Abstract Title: A Phase 1b/2 study of batiraxcept (AVB-S6-500) in combination with cabozantinib, cabozantinib and nivolumab, and as monotherapy in patients with advanced or metastatic clear cell renal cell carcinoma (NCT04300140)
Abstract Number: TPS4599 (Trials in Progress poster – No data presented)
Poster Session: Genitourinary Cancer—Kidney and Bladder
Session Date: Saturday, June 4, 2022, 1:15 PM – 4:15 PM CDT
Of note, 100% of patients had received a prior immunotherapy, 77% of the patients were in the IMDC (International Metastatic RCC Database Consortium) Risk Score of intermediate or poor, and 39% of the patients had received 2 or more prior lines of therapy prior to study entry.

A summary of the interim Phase 1b results include (as of April 30, 2022, the cut-off date):

Batiraxcept 15 mg/kg in combination with cabozantinib 60 mg has a manageable safety profile in previously treated ccRCC; no dose-limiting toxicities have been observed; a similar safety profile was observed across the 15 mg/kg and 20 mg/kg dose cohorts.
Batiraxcept given every 2 weeks suppressed serum GAS6 to below the level of quantitation in 25/26 patients (1 patient did not have an assessment), showing a clear pharmacokinetic (PK)/pharmacodynamic (PD) relationship; 23/26 patients had batiraxcept trough levels above the minimally efficacious concentration of 13.8 mg/L by Cycle 2.
The confirmed + unconfirmed response rate in the total population was 46% with a 50% confirmed response rate in the 15mg/kg (RP2D) batiraxcept group.
The proportion of patients in the total population who were progression free at 7 months was 71%.
The proportion of patients in the total population who had a duration of response of at least 7 months was 75%.
A baseline biomarker enriched the confirmed response rate in the RP2D (15mg/kg) biomarker high population to 67%, increased the proportion of patients progression free at 7 months to 91% and increased the proportion of patients who had a duration of response of at least 7 months to 80%.
58% (15/26) of total population achieved a better response on the batiraxcept trial than they did with their therapy prior to study entry, which was only 23%.
The safety and clinical activity of this combination together with PK/PD data support a RP2D of 15 mg/kg.

On May 26, 2022 Amgen (NASDAQ: AMGN) reported that it will present new data from across its broad oncology innovative medicines and biosimilars portfolio and robust pipeline at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting from June 3-7 in Chicago and virtually (Press release, Amgen, MAY 26, 2022, View Source [SID1234615068]).

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Oral presentations will showcase Amgen’s medicines for both lung and colorectal cancers with a plenary session highlighting the results from the PARADIGM Phase 3 head-to-head trial conducted by Takeda Pharmaceutical Company in Japan comparing the efficacy of Vectibix (panitumumab) versus Avastin (bevacizumab), both used in combination with chemotherapy, in patients with previously untreated RAS wild-type metastatic colorectal cancer (mCRC)*. Data from a pooled analysis of CodeBreaK 100, representing the largest evaluation of mechanisms of acquired resistance in KRASG12C inhibition, offer new insights to help inform combination treatment approaches with LUMAKRAS/ LUMYKRAS.

"Amgen continues to lead the science in KRASG12C inhibition and is committed to advancing research into how LUMAKRAS can improve outcomes for more patients, including further defining resistance patterns to guide our robust combination treatment development program," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "In addition, the compelling head-to-head results further reinforcing the important role Vectibix plays in the treatment of colorectal cancer, illustrate how Amgen is expanding the impact of our first-in-class therapies in some of the most challenging-to-treat cancers."

In the CodeBreaK 100 analysis, investigators evaluated patterns of resistance to LUMAKRAS in patients with NSCLC (n=67) and CRC (n=45) at disease progression. At least one newly acquired genomic alteration at progression was detected in 19 (28%) NSCLC patients and in 33 (73%) CRC patients. The alterations were heterogeneous in both tumor types, with variants detected across multiple genes and pathways.

Other research highlights being presented on Amgen Oncology’s growing precision medicine and T-cell engager pipeline include study updates on bemarituzumab, a potential first-in-class therapy for a subset of gastric and gastroesophageal cancers that overexpress fibroblast growth factor receptor 2 (FGFR2b), AMG 193, a small molecule methylthioadenosine (MTA) cooperative protein arginine methyltransferase 5 (PRMT5) inhibitor being investigated for the treatment of solid tumors, and tarlatamab, an investigational, first-in-class half-life extended (HLE) bispecific T-cell engager (BiTE) molecule that is uniquely designed to target delta-like ligand 3 (DLL3) in neuroendocrine cancers.

Additional information on Amgen’s abstracts is available on the ASCO (Free ASCO Whitepaper) website.

Abstracts and Presentation Times:

Amgen Sponsored Abstracts

LUMAKRAS/LUMYKRAS (sotorasib)

Largest evaluation of acquired resistance to sotorasib in KRAS p.G12C-mutated non-small cell lung cancer (NSCLC) and colorectal cancer (CRC): plasma biomarker analysis of CodeBreaK 100
Abstract #102, Oral Presentation Session: Clinical Science Symposium, ctDNA: Dawn of a New Era, Saturday, June 4 from 8:00-9:30 a.m. CDT

First data for sotorasib in patients with pancreatic cancer with KRAS p.G12C mutation: a phase 1/2 study evaluating efficacy and safety
Abstract #360490, Plenary Series: Rapid Abstract Updates, Sunday, June 5 from 4:30-6:00 p.m. CDT

Trial-in-progress: A phase 2 study of sotorasib as first-line treatment in patients with stage IV non-small cell lung cancer (NSCLC) whose tumors harbor a KRAS p.G12C mutation (CodeBreaK 201)
Abstract #TPS9150, Poster Presentation Session: Lung Cancer—Non-Small Cell Metastatic, Monday, June 6 from 8:00-11:00 a.m. CDT
IMLYGIC (talimogene laherparepvec)

Primary analysis of a phase 2, open-label, multicenter trial of talimogene laherparepvec (T-VEC) plus pembrolizumab (pembro) for the treatment (Tx) of patients (pts) with advanced melanoma (MEL) who progressed on prior anti–PD-1 therapy: MASTERKEY-115
Abstract #9518, Poster Discussion Session: Melanoma/Skin Cancers, Monday, June 6 from 4:30-6:00 p.m. CDT
Investigational BiTE Platform

Trial-in-progress: Phase 2 study of tarlatamab, a DLL3-targeting half-life extended bispecific T-cell engager (HLE BiTE) immuno-oncology therapy, in relapsed/refractory small cell lung cancer (SCLC)
Abstract #TPS8603, Poster Presentation Session: Lung Cancer-Non-small cell local-regional/small cell/other thoracic cancers, Monday, June 6 from 8:00-11:00 a.m. CDT
Trial-in-progress: A phase 1 study of AMG 509 in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC)
Abstract #TPS5101, Poster Session: Genitourinary Cancer—Prostate, Testicular, and Penile, Monday, June 6 from 1:15-4:15 p.m. CDT
AMG 193

Trial-in-progress: Design and rationale of a phase 1 dose-escalation study of AMG 193, a methylthioadenosine (MTA)-cooperative PRMT5 inhibitor, in patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors
Abstract #TPS3167, Poster Presentation Session: Developmental Therapeutics—Molecularly Targeted Agents and Tumor Biology, Sunday, June 5 from 8:00-11:00 a.m. CDT
Bemarituzmab

Trial-in-progress: Phase 3 study of bemarituzumab + mFOLOFOX6 versus placebo + mFOLFOX6 in previously untreated advanced gastric or gastroesophageal junction (GEJ) cancer with FGFR2b overexpression (FORTITUDE-101)
Abstract #TPS4164, Poster Presentation: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary, Saturday, June 4 from 8:00-11:00 a.m. CDT
Trial-in-progress: Phase 1b/3 study of bemarituzumab + mFOLFOX6 + nivolumab vs mFOLFOX6 + nivolumab in previously untreated advanced gastric and gastroesophageal junction (GEJ) cancer with FGFR2b overexpression (FORTITUDE-102)
Abstract #TPS4165, Poster Presentation: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary, Saturday, June 4 from 8:00-11:00 a.m. CDT
Partner-Led Abstracts

Vectibix (panitumumab)

Plasma RAS dynamics and anti-EGFR rechallenge efficacy in patients with RAS/BRAF wild-type metastatic colorectal cancer: REMARRY and PURSUIT trials
Abstract #3518, Poster Discussion Session: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Resistance mechanisms to anti-EGFR therapy in RAS/RAF wildtype colorectal cancer varies by regimen and line of therapy
Abstract #3554, Poster Presentation: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6 as first-line treatment in patients with RAS wild-type metastatic colorectal cancer (mCRC): results from the phase 3 PARADIGM trial
Abstract #LBA1, Plenary Session: Primary Track: Special Sessions, Sunday, June 5 from 1:00-4:00 p.m. CDT
Prolia (denosumab)

Long-term outcomes of adjuvant denosumab in breast cancer: Fracture reduction and survival results from 3,425 patients in the randomised, double-blind, placebo-controlled ABCSG-18 trial
Abstract #507, Oral Presentation: Breast Cancer—Local/Regional/Adjuvant, Tuesday, June 7 from 9:45 a.m.-12:45 p.m. CDT
Investigator Sponsored Studies (ISS)

IMLYGIC (talimogene laherparepvec)

Trial-in-progress: Neo-adjuvant T-VEC plus nivolumab combination therapy for resectable early- stage or metastatic (IIIB-IVM1a) melanoma with injectable disease: The NIVEC trial
Abstract #TPS9607, Poster Session: Melanoma/Skin Cancers, Monday, June 6 from 1:15-4:15 p.m. CDT
KYPROLIS (carfilzomib)

A phase II study of daratumumab with weekly carfilzomib, pomalidomide, and dexamethasone in relapsed and refractory multiple myeloma
Abstract #8012, Poster Discussion Session: Hematologic Malignancies – Plasma Cell Dyscrasia, Saturday, June 4 from 4:30-6:00 p.m. CDT
ATLAS: A phase 3 randomized trial of carfilzomib, lenalidomide, and dexamethasone versus lenalidomide alone after stem-cell transplant for multiple myeloma
Abstract #8001, Oral Abstract Session: Hematologic Malignancies—Plasma Cell Dyscrasia, Sunday, June 5 from 8:00-11:00 a.m. CDT
Daratumumab carfilzomib lenalidomide and dexamethasone as induction therapy in high-risk, transplant-eligible patients with newly diagnosed myeloma: Results of the phase 2 study IFM 2018-04
Abstract #8002, Oral Abstract Session: Hematologic Malignancies—Plasma Cell Dyscrasia, Sunday, June 5 from 8:00-11:00 a.m. CDT
LUMAKRAS/LUMYKRAS (sotorasib)

Trial-in-progress: A phase Ib/II study of sotorasib combined with chemotherapy for second-line treatment of KRAS p. G12C mutated advanced pancreatic cancer
Abstract #TPS4194, Poster Session: Gastrointestinal Cancer—Gastroesophageal, Pancreatic, and Hepatobiliary, Saturday, June 4 from 8:00-11:00 a.m. CDT
Predictors of biomarker testing among patients (pts) with metastatic non-small cell lung cancer (mNSCLC)
Abstract #9130, Poster Session: Lung Cancer—Non-Small Cell Metastatic, Monday, June 6 from 8:00-11:00 a.m. CDT
Vectibix (panitumumab)

Phase 2 study of anti-EGFR rechallenge therapy with panitumumab with or without trametinib in advanced colorectal cancer
Abstract #3520, Poster Discussion Session: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Negative hyperselection for mutations associated with anti-EGFR antibody resistance in RAS wildtype metastatic colorectal cancer (mCRC): Evaluation of the PANAMA trial (AIO-KRK-0212, maintenance therapy with 5-FU, folinic acid (FU/FA) with or without panitumumab)
Abstract #3536, Poster Session: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Consensus molecular subtypes (CMS) as prognostic & predictive biomarkers of panitumumab (Pmab), fluorouracil & folinic acid (FU/FA) or FU/FA maintenance therapy following Pmab-FOLFOX induction in RAS wildtype metastatic colorectal cancer (mCRC) – PANAMA trial (AIO-KRK-0212)
Abstract #3537, Poster Session: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Impact of age and gender on the efficacy & safety of panitumumab plus fluorouracil & folinic acid versus fluorouracil and folinic acid alone as maintenance therapy in RAS WT metastatic colorectal cancer (mCRC). Subgroup analysis of the PANAMA-study (AIO-KRK-0212)
Abstract #3567, Poster Session: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Predictive and prognostic value of carcinoembryonic antigen (CEA) on maintenance therapy with 5-fluoruracil/leucovorin plus panitumumab or 5-fluoruracil/leucovorin alone in RAS wildtype metastatic colorectal cancer: Evaluation of the phase II PanaMa trial (AIO KRK 0212)
Abstract # 3587, Poster Session: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 8:00-11:00 a.m. CDT
Modified FOLFOXIRI plus panitumumab (mFOLFOXIRI/PAN) versus mFOLFOX6/PAN as initial treatment of unresectable RAS and BRAF wild-type metastatic colorectal cancer (mCRC) patients: results of the phase III randomized TRIPLETE study by GONO
Abstract #LBA3505, Oral Presentation: Gastrointestinal Cancer—Colorectal and Anal, Saturday, June 4 from 9:45 a.m.–12:45 p.m. CDT
Randomized intermittent or continuous panitumumab plus FOLFIRI (FOLFIRI/PANI) for first-line treatment of patients (pts) with RAS/BRAF wild-type metastatic colorectal cancer (mCRC): the IMPROVE study
Abstract #3503, Oral Abstract Session: Gastrointestinal Cancer—Colorectal and Anal, Monday, June 6 from 9:45 a.m.-12:45 p.m. CDT
XGEVA (denosumab)

Trial-in-progress: A phase 3 study to determine the breast cancer risk reducing effect of denosumab in women carrying a germline BRCA1 mutation (BRCA-P Study)
Abstract #TPS10616, Poster Session: Prevention, Risk Reduction, and Hereditary Cancer, Monday, June 6 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, including triplets, with clinical trial sites spanning five continents. To date, over 4,000 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 and Switzerland and in Australia, Brazil, Canada, and Great Britain under the FDA’s Project Orbis. Through Project Orbis, Amgen also has Marketing Authorization Applications (MAAs) for sotorasib in review in Israel and Singapore. Additionally, Amgen has submitted MAAs in Argentina, Colombia, Hong Kong, Kuwait, Malaysia, Mexico, Qatar, Saudi Arabia, Taiwan, 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 8% 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 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.

CodeBreaK 100, the Phase 1 and 2, first-in-human, open-label multicenter study, enrolled patients with KRAS G12C-mutant solid tumors.9 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.2 The Phase 2 trial in colorectal cancer (CRC) is fully enrolled and results have been published.10

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.11

Amgen also has several Phase 1b studies investigating sotorasib monotherapy and sotorasib combination therapy across various advanced solid tumors (CodeBreaK 101) open for enrollment.12 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).13

For information, please visit www.hcp.codebreaktrials.com.

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, 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 ≥ 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 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.

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.

At Amgen, we’re advancing oncology at the speed of life.