On May 26, 2022 Legend Biotech Corporation (NASDAQ: LEGN) (Legend Biotech), a global biotechnology company developing, manufacturing and commercializing novel therapies to treat life-threatening diseases, reported that the European Commission (EC) has granted conditional marketing authorization of CARVYKTI (ciltacabtagene autoleucel; cilta-cel) for the treatment of adults with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior therapies, including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 antibody, and have demonstrated disease progression on the last therapy. Legend Biotech entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel in December 2017 (Press release, Legend Biotech, MAY 26, 2022, View Source [SID1234615116]).

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CARVYKTI is a chimeric antigen receptor T-cell (CAR-T) therapy featuring two B-cell maturation antigen (BCMA)-targeting single domain antibodies.1 CAR-T therapy is specifically developed for each individual patient, and it is administered as a single infusion.1,2

"The approval of CARVYKTI by the European Commission marks Legend’s first approval in the region and is a significant milestone as we advance our commitment to bring innovative cell therapies to patients with the highest unmet need," said Ying Huang, Ph.D., Chief Executive Officer of Legend Biotech. "The CARTITUDE-1 data showed that CARVYKTI provides the potential for long, treatment-free intervals for heavily pre-treated patients, and is a valuable treatment option for patients with multiple myeloma. We look forward to working with Janssen to bring this new option to patients across Europe."

This approval was supported by the pivotal CARTITUDE-1 study, including patients who had received a median of six prior treatment regimens (range, 3-18), and had previously received an IMiD, PI and anti-CD38 monoclonal antibody.3 Findings showed that at a median duration of 18 months follow-up (range, 1.5-30.5), a one-time treatment with cilta-cel resulted in deep and durable responses, with 98 percent (95 percent confidence interval [CI], 92.7-99.7) of patients with RRMM responding to therapy (98 percent overall response rate [ORR] (N=97)).3,4 Notably, 80 percent of the patients achieved stringent complete response (sCR), a measure in which a physician is unable to observe any signs or symptoms of disease via imaging or other tests after treatment.3

The safety of cilta-cel was evaluated in 179 adult patients across two open-label clinical trials (MMY2001 and MMY2003). The most common adverse reactions (≥20 percent) were neutropenia (91 percent), cytokine release syndrome (CRS) (88 percent), pyrexia (88 percent), thrombocytopenia (73 percent), anemia (72 percent), leukopenia (54 percent), lymphopenia (45 percent), musculoskeletal pain (43 percent), hypotension (41 percent), fatigue (40 percent), transaminase elevation (37 percent), upper respiratory tract infection (32 percent), diarrhea (28 percent), hypocalcemia (27 percent), hypophosphatemia (26 percent), nausea (26 percent), headache (25 percent), cough (25 percent), tachycardia (23 percent), chills (23 percent), encephalopathy (22 percent), decreased appetite (22 percent), oedema (22 percent), and hypokalemia (20 percent).4

"There continues to be an unmet need for patients with relapsed or refractory multiple myeloma who have exhausted existing treatment options. Data from the CARTITUDE-1 trial have shown that cilta-cel provides deep and durable responses for heavily pre-treated patients. Today’s approval by the European Commission reinforces the potential of this new treatment option for multiple myeloma patients in Europe," said Hermann Einsele, Full Professor of Internal Medicine and Director of the Medizinische Klinik und Poliklinik II of the Julius Maximilian University, Würzburg, Germany.*

As a highly personalized medicine, where a patient’s own T-cells are reprogrammed to target and kill cancer cells, administration of CAR-T therapy requires extensive training, preparation, and certification to ensure the highest quality product and experience for patients.2 Through a phased approach, Legend Biotech’s strategic partner, Janssen, will work diligently to activate a limited network of certified treatment centers and will aim to increase availability of cilta-cel across Europe, in an effort to provide oncologists and patients with treatment in a reliable manner.

This EC Marketing Authorization follows the approval of CARVYKTI by the U.S. Food and Drug Administration (FDA) on February 28, 2022.

*Hermann Einsele, M.D., FRCP has not been paid for contributing to this press release.

About CARVYKTI (ciltacabtagene autoleucel; cilta-cel)

CARVYKTI is a BCMA-directed, genetically modified autologous T-cell immunotherapy, which involves reprogramming a patient’s own T-cells with a transgene encoding a chimeric antigen receptor (CAR) that identifies and eliminates cells that express BCMA.4 BCMA is primarily expressed on the surface of malignant multiple myeloma B-lineage cells, as well as late-stage B-cells and plasma cells.4 The CARVYKTI CAR protein features two BCMA-targeting single domain antibodies designed to confer high avidity against human BCMA.4 Upon binding to BCMA-expressing cells, the CAR promotes T-cell activation, expansion, and elimination of target cells.4

In December 2017, Legend Biotech Corporation entered into an exclusive worldwide license and collaboration agreement with Janssen Biotech, Inc. (Janssen) to develop and commercialize cilta-cel.5

In April 2021, Legend announced the submission of a Marketing Authorisation Application to the European Medicines Agency seeking approval of cilta-cel for the treatment of patients with relapsed or refractory multiple myeloma. In addition to U.S. Breakthrough Therapy Designation granted in December 2019, cilta-cel also received Breakthrough Therapy Designation in China in August 2020. In February 2019, cilta-cel received Orphan Drug Designation from the U.S. FDA from the European Commission in February 2020, and from the Pharmaceuticals and Medicinal Devices Agency (PMDA) in Japan in June 2020. In May 2022, the Committee for Orphan Medicinal Products recommended by consensus that the orphan designation for cilta-cel be maintained, on the basis of clinical data demonstrating improved and sustained complete response rates following treatment.6 Cilta-cel was approved the U.S. Food and Drug Administration (FDA) in February 2022.5

About CARTITUDE-1

CARTITUDE-1 (NCT03548207)7 is an ongoing Phase 1b/2, open-label, single arm, multi-center trial evaluating cilta-cel for the treatment of adult patients with relapsed or refractory multiple myeloma, who previously received at least three prior lines of therapy including a proteasome inhibitor (PI), an immunomodulatory agent (IMiD) and an anti-CD38 monoclonal antibody. Of the 97 patients enrolled in the trial, 99 percent were refractory to the last line of treatment and 88 percent were triple-class refractory, meaning their cancer did not respond, or no longer responds, to an IMiD, a PI and an anti-CD38 monoclonal antibody.4

About Multiple Myeloma

Multiple myeloma is an incurable blood cancer that starts in the bone marrow and is characterized by an excessive proliferation of plasma cells.8 In Europe, it is estimated that more than 50,900 people were diagnosed with multiple myeloma in 2020, and approximately 32,500 patients died.9 While some patients with multiple myeloma have no symptoms at all, most patients are diagnosed due to symptoms that can include bone problems, low blood counts, calcium elevation, kidney problems or infections.10 Although treatment may result in remission, unfortunately, patients will most likely relapse.11 Patients who relapse after treatment with standard therapies, including protease inhibitors, immunomodulatory agents, and an anti-CD38 monoclonal antibody, have poor prognoses and few treatment options available.12,13

On May 6, 2022 Pionyr Immunotherapeutics, Inc., a company developing first-in-class Myeloid TuningTM antibody therapeutics that enhance the body’s antitumor immunity by altering, or "tuning," immune cells within the tumor microenvironment, reported that PY314, a monoclonal antibody targeting TREM2 (triggering receptor expressed on macrophages 2), was safe and well-tolerated in a Phase 1a dose-escalation study as a single agent and in combination with pembrolizumab at its label-approved dose (Press release, Pionyr Immunotherapeutics, MAY 26, 2022, View Source [SID1234615132]). A maximum tolerated dose (MTD) was not observed over the range of PY314 doses tested and a dose for study expansion was recommended based on an analysis of clinical data (including PK exposure) in the context of supportive preclinical data models. The study will be featured in a poster presentation at the 2022 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting, held June 3-7 virtually and in Chicago.

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"Pionyr developed PY314 to precisely bind human TREM2 and retune the tumor microenvironment by driving the selective depletion of TREM2 positive tumor-associated macrophages. Removing these macrophages shifts the balance of myeloid cells towards more pro-inflammatory populations and is expected to increase and promote anti-tumor immune responses," said Leonard Reyno, EVP and Chief Medical Officer of Pionyr Immunotherapeutics. "We have applied what we have learned from the Phase 1a study to identify a recommended dose for Phase 1b expansion studies. We have already begun enrolling patients in these studies and expect to have new data this year and into 2023."

Safety and Tolerability as a Monotherapy and in Combination with Pembrolizumab Support Additional Clinical Studies

The Phase 1a dose-escalation study of PY314 was a non-randomized, open-label study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of PY314 as a single agent and in combination with checkpoint inhibitor pembrolizumab in 28 subjects with advanced solid tumors. Dosing was intravenous and administered once every three weeks. Four predefined dose levels of PY314 were delivered both as a single agent and in combination with pembrolizumab. No dose-limiting toxicities, drug-related serious adverse reactions, or high-grade treatment-related adverse events (TRAEs) that resulted in treatment discontinuance were seen. Twelve patients experienced at least one TRAE, and these were low-grade in all but one subject who experienced a treatment-related immune system disorder. Eight patients experienced serious adverse events, all unrelated to treatment.

Linear Dose-Response Observed and Recommended Dose for Expansion Studies Determined

PY314 pharmacokinetics were linear and dose-proportional, with a half-life of five to nine days and no evidence of interference by pembrolizumab. The best radiographic response was stable disease, observed in eleven subjects (39.3%), which ranged in duration from nine to 42 weeks. Ten mg/kg PY314 was determined to be the recommended dose for expansion. Five expansion cohorts in patients with metastatic refractory solid tumors (triple-negative or HR-positive HER2 negative metastatic breast cancer, non-small cell lung cancer, renal cell carcinoma, colorectal cancer, ovarian cancer) are enrolling. Information about the ongoing Phase 1b expansion study is available at www.clinicaltrials.gov.

Poster Presentation at ASCO (Free ASCO Whitepaper) 2022

The poster titled, "A Phase 1a Dose Escalation Study of PY314, a TREM2 (Triggering Receptor Expressed on Myeloid Cells 2)-Targeting Monoclonal Antibody," will be featured in a poster session at the ASCO (Free ASCO Whitepaper) 2022 Annual Meeting on Sunday, June 5, 2022, 8:00 AM-11:00 AM CDT. The abstract is currently available on the ASCO (Free ASCO Whitepaper) 2022 website here, and the poster will be available on the Pionyr company website here after the completion of the ASCO (Free ASCO Whitepaper) poster session.

About Myeloid TuningTM

Pionyr has developed a therapeutic platform called Myeloid Tuning, a process that rebalances the tumor microenvironment (TME) to promote anti-tumor immunity. Myeloid cells are a type of immune cell and are part of a family of cell types that play an important role in both the activation and suppression of the immune response to cancer.

One such critical type of myeloid cell, tumor-associated macrophages (TAM), are a key component of the TME. TAMs are generally categorized into two functionally contrasting subtypes called M1-like and M2-like macrophages: M1-like typically exerts anti-tumor functions, including directly mediating antibody-dependent cell-mediated cytotoxicity (ADCC) to kill tumor cells; M2-like macrophages can promote the occurrence and metastasis of tumor cells, inhibit T cell-mediated anti-tumor immune response, promote tumor angiogenesis and lead to tumor progression.

Myeloid Tuning TM effectively describes the mechanism of introducing agents that shift the balance of inhibitory myeloid cells – including M2-like TAMs – towards more inflammatory M1-like TAMs to promote anti-tumor immune responses in the TME and destroy solid tumors.

About PY314

PY314 is a humanized IgG1 afucosylated monoclonal antibody, delivered by intravenous infusion, that binds Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) on the surface of immunosuppressive, pro-tumorigenic myeloid cells. It is designed to deplete TREM2-expressing TAMs, leading to productive anti-tumor immunity. Preclinical data generated by Pionyr suggest that when TAMs are depleted from tumors, pro-inflammatory, anti-tumorigenic immune cells such as CD8 T-cells, natural killer (NK), and M1-like macrophages become activated and penetrate tumors leading to tumor destruction. PY314 is currently being evaluated in a Phase 1b dose-expansion study as a single agent and in combination with pembrolizumab (Keytruda) as a treatment for refractory solid tumors and gynecologic cancer, colorectal cancer, lung adenocarcinoma, renal cell carcinoma, triple-negative breast cancer, hormone receptor/growth factor receptor-negative breast cancer, and ovarian cancer.

On May 26, 2022 Quest Diagnostics Incorporated (NYSE: DGX), the world’s leading provider of diagnostic information services, reported that it is scheduled to speak at the Jefferies Healthcare Conference (Press release, Quest Diagnostics, MAY 26, 2022, View Source [SID1234615148]). Steve Rusckowski, Chairman, CEO and President and Jim Davis, CEO-elect, will discuss the company’s vision, goals, and capital deployment strategies. The presentation is scheduled for Friday, June 10, 2022, at 11:00 a.m. Eastern Time.

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The presentation and Q&A session will be webcast live during the conference and will be available on the company’s investor relations page which can be accessed at ir.QuestDiagnostics.com. In addition, the archived webcast will be available within 24 hours after the conclusion of the live event and will remain available until August 10, 2022.

On May 26, 2022 Race Oncology Limited ("Race") reported the dose escalation Phase 1b stage of the relapsed or refractory Acute Myeloid Leukaemia (R/R AML) trial running at the Chaim Sheba Medical Centre, Israel has successfully completed after the treatment of the first six patients (Press release, Race Oncology, MAY 26, 2022, View Source [SID1234615165]).

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The six patients were heavily pre-treated and had received a median of four prior lines of AML treatment (range 2-8).

By design, the primary endpoint of the initial phase of this 2-stage clinical trial is establishing the recommended dose to be used in the subsequent Phase 2 expansion (efficacy) stage. This first stage requires identifying the treatment dose level that achieves two or fewer dose-limiting toxicities (DLTs) from six consecutively treated patients. In the initial six patients treated, two DLTs were reported (one Grade 3 elevated liver enzymes and one Grade 5 infection). Both DLTs occurred in the most heavily pre-treated patients who had received five and eight prior lines of treatment, respectively.

"The positive results from the first stage of this trial in such a heavily pre-treated relapsed or refractory Acute Myeloid Leukaemia population is encouraging, especially with three of the patients being subsequently bridged to transplant. We look forward to the next stage of this study which, together with data from the EMD AML Trial (RAC-006) which is soon to commence recruitment in Australia, is extending our understanding of Zantrene in a modern AML setting."

Race CMO Dr David Fuller
Efficacy results in this refractory patient population were very encouraging, with one patient showing a complete response (CR) based on morphology, two patients having a partial response (PR) including one with extramedullary disease, two showing no response (NR), and one patient not assessable (NA) due to death from infection. Infection is a known side effect of all intensive chemotherapeutic regimens and is one of the leading causes of death in AML patients.

"The encouraging results of our Phase I study with Zantrene monotherapy and moreover the current Phase II study altogether with Zantrene in combination in extremely heavily treated advanced high risk AML patients are encouraging and may indicate a role for Zantrene in modern AML treatment paradigm to the benefit of our patients."

Study Lead Prof Arnon Nagler
Three patients (1 CR and 2 PR) were bridged to an allogeneic stem cell transplant. Bridging a patient to transplant is an important positive outcome in AML treatment as it offers the patient the potential of long-term remission. Of note, these three patients had all received less than five prior lines of treatment. Poor or no response to known efficacious treatments is common and expected in heavily pre-treated cancer patients.

"We are very excited about the positive data from the first stage of this trial in such a heavily pre-treated R/R AML population, and we now look forward to the next phase, where we expect to see more patients respond favourably and with a consistently tolerable side effect profile. It appears that bridging to transplantation with long-term disease control can be achieved with confidence, given we can since perceive that the side effects reverse within a few weeks of the course being completed."

Race Clinical Advisory Board Chair Prof Borje Andersson
The trial will now progress to the Phase 2 efficacy (expansion) stage using a 4-day schedule of Zantrene (bisantrene dihydrochloride) in combination with fludarabine and clofarabine.

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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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.