Arcellx Announces Continued Robust Long-Term Responses from Its CART-ddBCMA (anito-cel) Phase 1 Expansion Trial in Patients with Relapsed or Refractory Multiple Myeloma at ASH

On December 8, 2023 Arcellx, Inc. (NASDAQ: ACLX), a biotechnology company reimagining cell therapy through the development of innovative immunotherapies for patients with cancer and other incurable diseases, reported new clinical data from its Phase 1 expansion study of CART-ddBCMA, now known as anitocabtagene autoleucel (anito-cel). Anito-cel utilizes a novel D-Domain BCMA binder that is compact and stable, which results in a drug product with a high proportion of CAR+ cells and high-surface expression, potentially enhancing antigen binding and more efficient Multiple Myeloma cell killing (Press release, Arcellx, DEC 8, 2023, View Source [SID1234638319]).

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The data continue to demonstrate robust long-term responses with median duration of response, progression free survival (PFS), and overall survival rate not reached. The data are from an October 15, 2023 data cut, with median follow-up after anito-cel infusion of 26.5 months. These latest study findings will be presented as an oral presentation during the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on Monday, December 11, 2023 at 5 p.m. PT. The company also has a medical affairs booth (#748) in Hall E of the San Diego Convention Center.

As of October 15, 2023, 38 patients were evaluable for efficacy and safety analysis based on a median follow-up of 26.5 months following treatment. These evaluable patients comprised the dose escalation cohorts for the first dose level (100 (+/- 20) million CAR+ T cells, n=6) and the second dose level (300 (+/- 20) million CAR+ T cells, n=6), and a dose expansion cohort at 100 (+/- 20) million CAR+ T cells (n=26). The median dose administered to patients in the first dose level and dose expansion cohorts was 115 million CAR+ T cells. All patients evaluable for this analysis have poor prognostic factors with 38 of 38 (100%) patients triple-refractory, 26 of 38 (68%) penta-refractory, and 34 of 38 (89%) refractory to last line of treatment under International Myeloma Working Group (IMWG) criteria. Additionally, 9 of 38 (24%) patients had high tumor burden with >60% bone marrow plasma (BMPC) cells, 13 of 38 (34%) patients had extra-medullary disease (EMD), and 11 of 38 (29%) patients had high-risk cytogenetics (Del 17p, t(14;16), t(4;14)) at screening/baseline. Further, 24 of 38 (63%) had at least one high-risk clinical feature, defined as presence of EMD, BMPC >60%, or Beta 2 microglobulin (B2M) >5.5 mg/L at screening/baseline. All 38 patients had at least three prior lines of therapy.

The interim anito-cel Phase 1 clinical results (October 15, 2023 cutoff date) demonstrate deep and durable responses in patients with poor prognostic factors.

All Patients:

Of the 38 evaluable patients with a median follow-up of 26.5 months


100% overall response rate (ORR) achieved in all patients per IMWG criteria


29 of 38 evaluable patients achieved a complete response (CR) or a stringent complete response (sCR) (>CR rate, 76%)


35 of 38 patients achieved a very good partial response or higher (>VGPR rate, 92%)

Of those evaluable for MRD testing to date (n=28), 25 (89%) were MRD-negative at a minimum of 10-5 sensitivity. Median duration of response, progression free survival (PFS), and overall survival were not reached at the time of the October 15, 2023 data cut. While median PFS is yet to be reached, the estimated Kaplan-Meier median progression free survival for the study population was 28 months at the time of the data cut with 26.5 months of median follow-up.

The Kaplan-Meier method estimated PFS rates for 6, 12, 18 and 24 months were 92%, 76%, 64% and 56%, respectively. Durable responses were also observed in patients with high-risk features (EMD, BMPC ≥60%, or B2M ≥5.5 mg/L at baseline) and high-risk cytogenetics.

Estimated PFS rates at 6, 12, 18, and 24- months by Kaplan-Meier method were:

PFS Rates (%)
6-month 12-month 18-month 24-month
All dosed (n=38)

92.1 75.9 63.7 56.0
Age ≥65 years (n=20)

95.0 85.0 74.3 61.3
High Risk Features* (n=24)

91.7 74.2 64.6 58.7
Extramedullary Disease (n=13)

92.3 67.1 67.1 57.5
High Risk Cytogenetics (n=11)

81.8 71.6 71.6 71.6

*
High risk features defined as presence of EMD, BMPC ≥60, or B2M ≥5.5 mg/L. Note: increased from prior presentation from 22 to 24 subjects as a result of database update based on ongoing data review.

Anito-cel dosed at RP2D (115 million (+/- 10) CAR+ T cells) continues to be well-tolerated at the time of the October 15, 2023 data cut:


Adverse events with anito-cel, including CRS and ICANS, were manageable


No cases of grade 3 (or greater) CRS and only one case (3%) of grade 3 ICANS event with no additional cases from previously reported


No tissue-targeted toxicities were observed


No cases of delayed neurotoxicity events or parkinsonian symptoms were observed

Matthew J. Frigault, M.D., anito-cel study investigator, Clinical Director of the Cellular Therapy Service at Mass General Cancer Center, and Assistant Professor at Harvard Medical School said, "It is encouraging to see continued deep and durable responses with anito-cel. While access to CAR-T treatment options for patients with multiple myeloma is expanding, it is still limited, and additional therapeutics can help close the treatment gap. In light of this encouraging clinical profile of anito-cel, I look forward to continuing to enroll patients in the iMMagine-1 study."

Arcellx’s Chairman and Chief Executive Officer, Rami Elghandour continued, "This latest data set further underscores our confidence in the potential of anito-cel to become a best-in-class treatment option for patients with relapsed or refractory multiple myeloma. Building on this momentum, we look forward to completing enrollment in our iMMagine-1 study and planning for commercial launch with our partners at Kite."

ASH Presentation Details:

Title: Phase 1 Study of CART-ddBCMA for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma: Results from at Least 1-Year Follow-up in All Patients

Speaker: Matthew J. Frigault, M.D., Clinical Director of the Cellular Therapy Service at Mass General Cancer Center, and Assistant Professor at Harvard Medical School

Session Name: 704. Cellular Immunotherapies: Early Phase and Investigational Therapies: CAR-T Cell Therapies for Multiple Myeloma and B Cell Lymphomas

Session Date: Monday, December 11, 2023

Session Time: 4:30—6:00 p.m. PT (Oral presentation for anito-cel will be at 5 p.m. PT)

Location: San Diego Convention Center, Room 6A, San Diego, California

Publication Number: 1023

A copy of the presentation can be accessed from Arcellx’s website at www.arcellx.com on the Scientific Publications page.

Webcast Event:

Arcellx will host a live webcast event with an expert panel of clinicians to discuss the clinical results on Monday, December 11, 2023 at 8 p.m. PT. The event will be accessible from Arcellx’s website at www.arcellx.com in the Investors section. A replay of the webcast will be archived and available for 30 days following the event.

About Multiple Myeloma

Multiple Myeloma (MM) is a type of hematological cancer in which diseased plasma cells proliferate and accumulate in the bone marrow, crowding out healthy blood cells and causing bone lesions, loss of bone density, and bone fractures. These abnormal plasma cells also produce excessive quantities of an abnormal immunoglobulin fragment, called a myeloma protein (M protein), causing kidney damage and impairing the patient’s immune function. Multiple myeloma is the third most common hematological malignancy in the United States and Europe, representing approximately 10% of all hematological cancer cases and 20% of deaths due to hematological malignancies. The median age of patients at diagnosis is 69 years with one-third of patients diagnosed at an age of at least 75 years. Because MM tends to afflict patients at an advanced stage of life, patients often have multiple co-morbidities and toxicities that can quickly escalate and become life-endangering.

About anito-cel

Anito-cel, formerly known as CART-ddBCMA is Arcellx’s BCMA-specific CAR-modified T-cell therapy utilizing the company’s novel BCMA-targeting binding domain for the treatment of patients with relapsed or refractory multiple myeloma. Anito-cel is currently in a Phase 2 study. Arcellx’s proprietary binding domains are novel synthetic proteins designed to bind specific therapeutic targets. Anito-cel has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the U.S. Food and Drug Administration.

AMGEN HIGHLIGHTS HEMATOLOGY PORTFOLIO AT ASH 2023

On December 8, 2023 Amgen (NASDAQ:AMGN) reported the presentation of new data from its blood cancer portfolio and pipeline at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition, taking place from Dec. 9-12 in San Diego (Press release, Amgen, DEC 8, 2023, View Source [SID1234638318]).

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"Data at this year’s ASH (Free ASH Whitepaper) meeting illustrate the expanding potential of our innovative hematology medicines, BLINCYTO and KYPROLIS, as well as our commitment to providing additional treatment options with our biosimilar eculizumab," said David M. Reese, M.D., executive vice president of Research and Development at Amgen. "As the pioneer of T-cell engager technology and building on nearly a decade of real-world experience, we continue to advance our first-in-class BiTE molecule, BLINCYTO, into earlier lines of treatment where we have seen encouraging data in patients living with acute lymphoblastic leukemia."

Abstracts are available on the ASH (Free ASH Whitepaper) website.

Key Abstracts and Presentation Times:

Amgen Sponsored Abstracts

KYPROLIS (carfilzomib)

Real-World Outcomes for Relapsed or Refractory Multiple Myeloma Patients Treated with Lenalidomide and Daratumumab Sparing Triplet Regimens: A United States Retrospective Cohort Study
Abstract #4705, Session #652, Monday, December 11 from 6:00 – 8:00 p.m. PT
Eculizumab (investigational biosimilar ABP 959 candidate to SOLIRIS)

Efficacy of Parallel and Crossover Analysis As Well As Pharmacokinetic Similarity Were Confirmed between ABP 959 and Eculizumab Reference Product in Patients with PNH
Abstract #4092, Session #508, Monday, December 11 from 6:00 – 8:00 p.m. PT
Investigator Sponsored Studies

BLINCYTO (blinatumomab)

Chemotherapy-Free Combination of Blinatumomab and Ponatinib in Adults With Newly Diagnosed Philadelphia Chromosome–Positive Acute Lymphoblastic Leukemia: Updates From a Phase II Trial
Abstract #2827, Session #612, Sunday, December 10 from 6:00 – 8:00 p.m. PT
Phase II Study of Low-Intensity Chemotherapy (Mini-Hyper-CVD) and Ponatinib Followed by Blinatumomab and Ponatinib in Patients With Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia
Abstract #2868, Session #614, Sunday, December 10 from 6:00 – 8:00 p.m. PT
Assessment of Outcomes of Consolidation Therapy By Number of Cycles of Blinatumomab Received in Newly Diagnosed Measurable Residual Disease Negative Patients with B-Lineage Acute Lymphoblastic Leukemia: In the ECOG-ACRIN E1910 Randomized Phase III National Clinical Trials Network Trial*
Abstract #2877, Session #614, Sunday, December 10 from 6:00 – 8:00 p.m. PT
Phase 2 Trial of Mini-Hyper-CVD Plus Inotuzumab Ozogamicin, With or Without Blinatumomab, in Older Patients With Newly Diagnosed Philadelphia Chromosome-Negative B-Cell Acute Lymphoblastic Leukemia
Abstract #2878, Session #614, Sunday, December 10 from 6:00 – 8:00 p.m. PT
Pediatric Patients with High-Risk B-Cell ALL in First Complete Remission May Benefit from Less Toxic Immunotherapy with Blinatumomab – Results from Randomized Controlled Phase 3 Trial AIEOP-BFM ALL 2017
Abstract #825, Session #614, Monday, December 11 from 2:45 – 4:15 p.m. PT
Dose Reduced Chemotherapy in Sequence with Blinatumomab for Newly Diagnosed Older Patients with Ph/BCR::ABL Negative B-Precursor Adult Lymphoblastic Leukemia (ALL): Preliminary Results of the GMALL Bold Trial
Abstract #964, Session #614, Monday, December 11 from 4:30 – 6:00 p.m. PT
Updated Results from a Phase II Study of Hyper-CVAD, with or without Inotuzumab Ozogamicin, and Sequential Blinatumomab in Patients with Newly Diagnosed B-cell Acute Lymphoblastic Leukemia
Abstract #4245, Session #614, Monday, December 11 from 6:00 – 8:00 p.m. PT
Comparison between Dasatinib-Blinatumomab Vs Ponatinib-Blinatumomab Chemo-Free Strategy for Newly Diagnosed Ph+ Acute Lymphoblastic Leukemia Patients. Preliminary Results of the Gimema ALLL2820 Trial
Abstract #4249, Session #614, Monday, December 11 from 6:00 – 8:00 p.m. PT
*E1910 is sponsored by National Cancer Institute (NCI), part of the National Institutes of Health, and conducted by the NCI Funded National Clinical Trial Network.

KYPROLIS (carfilzomib)

Carfilzomib-Lenalidomide-Dexamethasone (KRd) Vs. Lenalidomide-Dexamethasone (Rd) in Newly Diagnosed Fit or Intermediate-Fit Multiple Myeloma Patients Not Eligible for Autologous Stem-Cell Transplantation (Phase III EMN20 Trial): Analysis of Sustained Undetectable Minimal Residual Disease (MRD)
Abstract #205, Session #653, Saturday, December 9 from 2:00 – 3:30 p.m. PT
Daratumumab, Carfilzomib, Lenalidomide, and Dexamethasone Induction and Consolidation with Tandem Transplant in High-Risk Newly Diagnosed Myeloma Patients: Final Results of the Phase 2 Study IFM 2018-04
Abstract #207, Session #653, Saturday, December 9 from 2:00 – 3:30 p.m. PT
GEM2017FIT Trial: Induction Therapy with Bortezomib-Melphalan and Prednisone (VMP) Followed By Lenalidomide and Dexamethasone (Rd) Versus Carfilzomib, Lenalidomide and Dexamethasone (KRd) Plus/Minus Daratumumab (D), 18 Cycles, Followed By Consolidation and Maintenance Therapy with Lenalidomide and Daratumumab: Phase III, Multicenter, Randomized Trial for Elderly Fit Newly Diagnosed Multiple Myeloma (NDMM) Patients Aged between 65 and 80 Years
Abstract #209, Session #653, Saturday, December 9 from 2:00 – 3:30 p.m. PT
Results of the Phase III Randomized Iskia Trial: Isatuximab-Carfilzomib-Lenalidomide-Dexamethasone Vs Carfilzomib-Lenalidomide-Dexamethasone As Pre-Transplant Induction and Post-Transplant Consolidation in Newly Diagnosed Multiple Myeloma Patients
Abstract #4, Plenary Scientific Session, Sunday, December 10 from 2:00 – 4:00 p.m. PT
About BLINCYTO (blinatumomab)
BLINCYTO is a BiTE (bispecific T-cell engager) immuno-oncology therapy that targets CD19 surface antigens on B cells. BiTE molecules fight cancer by helping the body’s immune system detect and target malignant cells by engaging T cells (a type of white blood cell capable of killing other cells perceived as threats) to cancer cells. By bringing T cells near cancer cells, the T cells can inject toxins and trigger cancer cell death (apoptosis). BiTE immuno-oncology therapies are currently being investigated for their potential to treat a wide variety of cancers.

BLINCYTO was granted breakthrough therapy and priority review designations by the U.S. Food and Drug Administration and is approved in the U.S. for the treatment of:

CD19-positive B-cell precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adults and pediatric patients.
relapsed or refractory CD19-positive B-cell precursor ALL in adults and pediatric patients.
In the European Union (EU), BLINCYTO is indicated as monotherapy for the treatment of:

adults with Philadelphia chromosome-negative CD19 positive relapsed or refractory B-precursor acute lymphoblastic leukemia (ALL). Patients with Philadelphia chromosome-positive B-precursor ALL should have failed treatment with at least 2 tyrosine kinase inhibitors (TKIs) and have no alternative treatment options.
adults with Philadelphia chromosome-negative CD19 positive B-precursor ALL in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1%.
pediatric patients aged 1 year or older with Philadelphia chromosome-negative CD19 positive B-precursor ALL which is refractory or in relapse after receiving at least two prior therapies or in relapse after receiving prior allogeneic hematopoietic stem cell transplantation.
pediatric patients aged 1 year or older with high-risk first relapsed Philadelphia chromosome-negative CD19 positive B-precursor ALL as part of the consolidation therapy.
BLINCYTO IMPORTANT SAFETY INFORMATION

WARNING: CYTOKINE RELEASE SYNDROME and NEUROLOGICAL TOXICITIES

Cytokine Release Syndrome (CRS), which may be life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO and treat with corticosteroids as recommended.
Neurological toxicities, which may be severe, life-threatening or fatal, occurred in patients receiving BLINCYTO. Interrupt or discontinue BLINCYTO as recommended.
Contraindications
BLINCYTO is contraindicated in patients with a known hypersensitivity to blinatumomab or to any component of the product formulation.

Warnings and Precautions

Cytokine Release Syndrome (CRS): CRS, which may be life-threatening or fatal, occurred in 15% of patients with R/R ALL and in 7% of patients with MRD-positive ALL. The median time to onset of CRS is 2 days after the start of infusion and the median time to resolution of CRS was 5 days among cases that resolved. Closely monitor and advise patients to contact their healthcare professional for signs and symptoms of serious adverse events such as fever, headache, nausea, asthenia, hypotension, increased alanine aminotransferase (ALT), increased aspartate aminotransferase (AST), increased total bilirubin (TBILI), and disseminated intravascular coagulation (DIC). The manifestations of CRS after treatment with BLINCYTO overlap with those of infusion reactions, capillary leak syndrome, and hemophagocytic histiocytosis/macrophage activation syndrome. If severe CRS occurs, interrupt BLINCYTO until CRS resolves. Discontinue BLINCYTO permanently if life-threatening CRS occurs. Administer corticosteroids for severe or life-threatening CRS.

Neurological Toxicities: Approximately 65% of patients receiving BLINCYTO in clinical trials experienced neurological toxicities. The median time to the first event was within the first 2 weeks of BLINCYTO treatment and the majority of events resolved. The most common (≥ 10%) manifestations of neurological toxicity were headache and tremor. Severe, life–threatening, or fatal neurological toxicities occurred in approximately 13% of patients, including encephalopathy, convulsions, speech disorders, disturbances in consciousness, confusion and disorientation, and coordination and balance disorders. Manifestations of neurological toxicity included cranial nerve disorders. Monitor patients for signs or symptoms and interrupt or discontinue BLINCYTO as outlined in the PI.

Infections: Approximately 25% of patients receiving BLINCYTO in clinical trials experienced serious infections such as sepsis, pneumonia, bacteremia, opportunistic infections, and catheter-site infections, some of which were life-threatening or fatal. Administer prophylactic antibiotics and employ surveillance testing as appropriate during treatment. Monitor patients for signs or symptoms of infection and treat appropriately, including interruption or discontinuation of BLINCYTO as needed.

Tumor Lysis Syndrome (TLS), which may be life-threatening or fatal, has been observed. Preventive measures, including pretreatment nontoxic cytoreduction and on-treatment hydration, should be used during BLINCYTO treatment. Monitor patients for signs and symptoms of TLS and interrupt or discontinue BLINCYTO as needed to manage these events.

Neutropenia and Febrile Neutropenia, including life-threatening cases, have been observed. Monitor appropriate laboratory parameters (including, but not limited to, white blood cell count and absolute neutrophil count) during BLINCYTO infusion and interrupt BLINCYTO if prolonged neutropenia occurs.

Effects on Ability to Drive and Use Machines: Due to the possibility of neurological events, including seizures, patients receiving BLINCYTO are at risk for loss of consciousness, and should be advised against driving and engaging in hazardous occupations or activities such as operating heavy or potentially dangerous machinery while BLINCYTO is being administered.

Elevated Liver Enzymes: Transient elevations in liver enzymes have been associated with BLINCYTO treatment with a median time to onset of 3 days. In patients receiving BLINCYTO, although the majority of these events were observed in the setting of CRS, some cases of elevated liver enzymes were observed outside the setting of CRS, with a median time to onset of 19 days. Grade 3 or greater elevations in liver enzymes occurred in approximately 7% of patients outside the setting of CRS and resulted in treatment discontinuation in less than 1% of patients. Monitor ALT, AST, gamma-glutamyl transferase, and TBILI prior to the start of and during BLINCYTO treatment. BLINCYTO treatment should be interrupted if transaminases rise to > 5 times the upper limit of normal (ULN) or if TBILI rises to > 3 times ULN.

Pancreatitis: Fatal pancreatitis has been reported in patients receiving BLINCYTO in combination with dexamethasone in clinical trials and the post-marketing setting. Evaluate patients who develop signs and symptoms of pancreatitis and interrupt or discontinue BLINCYTO and dexamethasone as needed.

Leukoencephalopathy: Although the clinical significance is unknown, cranial magnetic resonance imaging (MRI) changes showing leukoencephalopathy have been observed in patients receiving BLINCYTO, especially in patients previously treated with cranial irradiation and antileukemic chemotherapy.

Preparation and administration errors have occurred with BLINCYTO treatment. Follow instructions for preparation (including admixing) and administration in the PI strictly to minimize medication errors (including underdose and overdose).

Immunization: Vaccination with live virus vaccines is not recommended for at least 2 weeks prior to the start of BLINCYTO treatment, during treatment, and until immune recovery following last cycle of BLINCYTO.

Benzyl Alcohol Toxicity in Neonates: Serious adverse reactions, including fatal reactions and the "gasping syndrome", have been reported in very low birth weight (VLBW) neonates born weighing less than 1500 g, and early preterm neonates (infants born less than 34 weeks gestational age) who received intravenous drugs containing benzyl alcohol as a preservative. Early preterm VLBW neonates may be more likely to develop these reactions, because they may be less able to metabolize benzyl alcohol.

Use the preservative-free preparations of BLINCYTO where possible in neonates. When prescribing BLINCYTO (with preservative) for neonatal patients, consider the combined daily metabolic load of benzyl alcohol from all sources including BLINCYTO (with preservative), other products containing benzyl alcohol or other excipients (e.g., ethanol, propylene glycol) which compete with benzyl alcohol for the same metabolic pathway.

Monitor neonatal patients receiving BLINCYTO (with preservative) for new or worsening metabolic acidosis. The minimum amount of benzyl alcohol at which serious adverse reactions may occur in neonates is not known. The BLINCYTO 7-Day bag (with preservative) contains 7.4 mg of benzyl alcohol per mL.

Embryo-Fetal Toxicity: Based on its mechanism of action, BLINCYTO may cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Advise females of reproductive potential to use effective contraception during treatment with BLINCYTO and for 48 hours after the last dose.
Adverse Reactions

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

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

BLINCYTO (blinatumomab) is indicated for the treatment of CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in first or second complete remission with minimal residual disease (MRD) greater than or equal to 0.1% in adult and pediatric patients.
BLINCYTO is indicated for the treatment of relapsed or refractory CD19-positive B-cell precursor acute lymphoblastic leukemia (ALL) in adult and pediatric patients.
Please see BLINCYTO full Prescribing Information, including BOXED WARNINGS.

About BiTE Technology
BiTE (bispecific T-cell engager) technology is a targeted immuno-oncology platform that is designed to engage patient’s own T cells to any tumor-specific antigen, activating the cytotoxic potential of T cells to eliminate detectable cancer. The BiTE immuno-oncology platform has the potential to treat different tumor types through tumor-specific antigens. The BiTE platform has a goal of leading to off-the-shelf solutions, which have the potential to make innovative T cell treatment available to all providers when their patients need it. Amgen is advancing more than a dozen BiTE molecules across a broad range of hematologic malignancies and solid tumors, further investigating BiTE technology with the goal of enhancing patient experience and therapeutic potential. To learn more about BiTE technology, visit View Source

About KYPROLIS (carfilzomib)
Proteasomes play an important role in cell function and growth by breaking down proteins that are damaged or no longer needed.1 KYPROLIS has been shown to block proteasomes, leading to an excessive build-up of proteins within cells.2 In some cells, KYPROLIS can cause cell death, especially in myeloma cells because they are more likely to contain a higher amount of abnormal proteins.1,2

Since its first approval in 2012, more than 285,000 patients worldwide have received KYPROLIS. KYPROLIS is approved in the U.S. for the following:

for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy in combination with
Lenalidomide and dexamethasone; or
Dexamethasone; or
Daratumumab and dexamethasone.
Daratumumab and hyaluronidase-fihj and dexamethasone; or
Isatuximab and dexamethasone
as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.
KYPROLIS is also approved in Algeria, Argentina, Australia, Bahrain, Belarus, Brazil, Canada, Chile, Colombia, Ecuador, Egypt, European Union, Hong Kong, India, Israel, Japan, Jordan, Kazakhstan, Kuwait, Lebanon, Macao, Malaysia, Mexico, Morocco, New Zealand, Oman, Peru, Philippines, Qatar, Russia, Saudi Arabia, Serbia, Singapore, S. Africa, S. Korea, Switzerland, Taiwan, Thailand, Turkey and United Arab Emirates.

KYPROLIS IMPORTANT SAFETY INFORMATION

Cardiac Toxicities

New onset or worsening of pre-existing cardiac failure (e.g., congestive heart failure, pulmonary edema, decreased ejection fraction), cardiomyopathy, myocardial ischemia, and myocardial infarction including fatalities have occurred following administration of KYPROLIS. Some events occurred in patients with normal baseline ventricular function. Death due to cardiac arrest has occurred within one day of administration.
Monitor patients for signs or symptoms of cardiac failure or ischemia. Evaluate promptly if cardiac toxicity is suspected. Withhold KYPROLIS for Grade 3 or 4 cardiac adverse reactions until recovery, and consider whether to restart at 1 dose level reduction based on a benefit/risk assessment.
While adequate hydration is required prior to each dose in Cycle 1, monitor all patients for evidence of volume overload, especially patients at risk for cardiac failure. Adjust total fluid intake as clinically appropriate.
For patients ≥ 75 years, the risk of cardiac failure is increased. Patients with New York Heart Association Class III and IV heart failure, recent myocardial infarction, conduction abnormalities, angina, or arrhythmias may be at greater risk for cardiac complications and should have a comprehensive medical assessment prior to starting treatment with KYPROLIS and remain under close follow-up with fluid management.
Acute Renal Failure

Cases of acute renal failure, including some fatal renal failure events, and renal insufficiency (including renal failure) have occurred. Acute renal failure was reported more frequently in patients with advanced relapsed and refractory multiple myeloma who received KYPROLIS monotherapy. Monitor renal function with regular measurement of the serum creatinine and/or estimated creatinine clearance. Reduce or withhold dose as appropriate.
Tumor Lysis Syndrome

Cases of Tumor Lysis Syndrome (TLS), including fatal outcomes, have occurred. Patients with a high tumor burden should be considered at greater risk for TLS. Adequate hydration is required prior to each dose in Cycle 1, and in subsequent cycles as needed. Consider uric acid lowering drugs in patients at risk for TLS. Monitor for evidence of TLS during treatment and manage promptly, and withhold until resolved.
Pulmonary Toxicity

Acute Respiratory Distress Syndrome (ARDS), acute respiratory failure, and acute diffuse infiltrative pulmonary disease such as pneumonitis and interstitial lung disease have occurred. Some events have been fatal. In the event of drug-induced pulmonary toxicity, discontinue KYPROLIS.
Pulmonary Hypertension

Pulmonary arterial hypertension (PAH) was reported. Evaluate with cardiac imaging and/or other tests as indicated. Withhold KYPROLIS for PAH until resolved or returned to baseline and consider whether to restart based on a benefit/risk assessment.
Dyspnea

Dyspnea was reported in patients treated with KYPROLIS. Evaluate dyspnea to exclude cardiopulmonary conditions including cardiac failure and pulmonary syndromes. Stop KYPROLIS for Grade 3 or 4 dyspnea until resolved or returned to baseline. Consider whether to restart based on a benefit/risk assessment.
Hypertension

Hypertension, including hypertensive crisis and hypertensive emergency, has been observed, some fatal. Control hypertension prior to starting KYPROLIS. Monitor blood pressure regularly in all patients. If hypertension cannot be adequately controlled, withhold KYPROLIS and evaluate. Consider whether to restart based on a benefit/risk assessment.
Venous Thrombosis

Venous thromboembolic events (including deep venous thrombosis and pulmonary embolism) have been observed. Provide thromboprophylaxis for patients being treated with the combination of KYPROLIS with dexamethasone or with lenalidomide plus dexamethasone or with daratumumab and dexamethasone. The thromboprophylaxis regimen should be based on an assessment of the patient’s underlying risks.
For patients using hormonal contraception associated with a risk of thrombosis, consider an alternative method of effective contraception during treatment.
Infusion-Related Reactions

Infusion-related reactions, including life-threatening reactions, have occurred. Signs and symptoms include fever, chills, arthralgia, myalgia, facial flushing, facial edema, laryngeal edema, vomiting, weakness, shortness of breath, hypotension, syncope, chest tightness, or angina. These reactions can occur immediately following or up to 24 hours after administration. Premedicate with dexamethasone to reduce the incidence and severity of infusion-related reactions.
Hemorrhage

Fatal or serious cases of hemorrhage have been reported. Hemorrhagic events have included gastrointestinal, pulmonary, and intracranial hemorrhage and epistaxis. Promptly evaluate signs and symptoms of blood loss. Reduce or withhold dose as appropriate.
Thrombocytopenia

KYPROLIS causes thrombocytopenia with recovery to baseline platelet count usually by the start of the next cycle. Monitor platelet counts frequently during treatment. Reduce or withhold dose as appropriate.
Hepatic Toxicity and Hepatic Failure

Cases of hepatic failure, including fatal cases, have occurred. KYPROLIS can cause increased serum transaminases. Monitor liver enzymes regularly regardless of baseline values. Reduce or withhold dose as appropriate.
Thrombotic Microangiopathy

Cases of thrombotic microangiopathy, including thrombotic thrombocytopenic purpura/hemolytic uremic syndrome (TTP/HUS), including fatal outcome, have occurred. Monitor for signs and symptoms of TTP/HUS. Discontinue if diagnosis is suspected. If the diagnosis of TTP/HUS is excluded, KYPROLIS may be restarted. The safety of reinitiating KYPROLIS is not known.
Posterior Reversible Encephalopathy Syndrome (PRES)

Cases of PRES have occurred in patients receiving KYPROLIS. If PRES is suspected, discontinue and evaluate with appropriate imaging. The safety of reinitiating KYPROLIS is not known.
Progressive Multifocal Leukoencephalopathy (PML)

Cases of PML, including fatal cases, have occurred. In addition to KYPROLIS, other contributary factors may include prior or concurrent use of immunosuppressive therapy. Consider PML in any patient with new onset of or changes in pre-existing neurological signs or symptoms. If PML is suspected, discontinue and initiate evaluation for PML including neurology consultation.
Increased Fatal and Serious Toxicities in Combination with Melphalan and Prednisone in Newly Diagnosed Transplant-ineligible Patients

In a clinical trial of transplant-ineligible patients with newly diagnosed multiple myeloma comparing KYPROLIS, melphalan, and prednisone (KMP) vs bortezomib, melphalan, and prednisone (VMP), a higher incidence of serious and fatal adverse reactions was observed in patients in the KMP arm. KMP is not indicated for transplant-ineligible patients with newly diagnosed multiple myeloma.
Embryo-fetal Toxicity

KYPROLIS can cause fetal harm when administered to a pregnant woman.
Advise pregnant women of the potential risk to a fetus. Females of reproductive potential should use effective contraception during treatment with KYPROLIS and for 6 months following the final dose. Males of reproductive potential should use effective contraception during treatment with KYPROLIS and for 3 months following the final dose.
Adverse Reactions

The most common adverse reactions in the combination therapy trials: anemia, diarrhea, fatigue, hypertension, pyrexia, upper respiratory tract infection, thrombocytopenia, cough, dyspnea, and insomnia.
The most common adverse reactions in monotherapy trials: anemia, fatigue, thrombocytopenia, nausea, pyrexia, dyspnea, diarrhea, headache, cough, edema peripheral.
Please see accompanying full Prescribing Information.

INDICATIONS

KYPROLIS (carfilzomib) is indicated in combination with dexamethasone, or with lenalidomide plus dexamethasone, or with daratumumab plus dexamethasone, or with daratumumab plus hyaluronidase-fihj plus dexamethasone, or with isatuximab plus dexamethasone for the treatment of adult patients with relapsed or refractory multiple myeloma who have received one to three lines of therapy.
KYPROLIS is indicated as a single agent for the treatment of patients with relapsed or refractory multiple myeloma who have received one or more lines of therapy.

Sarah Cannon Research Institute to Present Latest Research Insights at the 2023 ASH Annual Meeting & Exposition

On December 7, 2023 Sarah Cannon Research Institute (SCRI) reported that more than 80 abstracts and presentations have been selected for inclusion at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting & Exposition. Hosted in San Diego and online from Dec. 9-12, the meeting is the year’s most comprehensive global hematology event (Press release, Sarah Cannon Research Institute, DEC 7, 2023, View Source [SID1234638277]).

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At this year’s ASH (Free ASH Whitepaper) Annual Meeting & Exposition, SCRI investigators, including physicians from The US Oncology Network, will discuss groundbreaking research in malignant and non-malignant blood cancer, CAR T-Cell therapy, real-world outcomes, and targeted immunotherapies.

"We look forward to sharing our research insights, including the latest developments in the treatment of sickle cell disease, immune effector cell therapy, and other novel therapies that are advancing the way we treat blood cancers and blood disorders," said Howard A. "Skip" Burris, III, MD, President, SCRI. "We are proud to share these important updates through the work of more than 65 investigators from across our network, which can only be done through the power of collaboration."

In November 2022, McKesson and HCA Healthcare formed a joint venture combining SCRI with former US Oncology Research, the research arm of The US Oncology Network. The collaboration brings together physicians who are actively enrolling patients into clinical trials at more than 250 locations in 24 states across the U.S. More than 65 investigators from the joint venture will present insights at this year’s Annual Meeting. Separately, Ontada, McKesson’s oncology real-world data and evidence, clinical education, and provider technology business, is also presenting two posters at the conference.

Featured presentations include:

Haydar Frangoul, MD, MS, Sarah Cannon Pediatric Hematology/Oncology & Cellular Therapy Program at TriStar Centennial Medical Center, is first author on an oral presentation titled, "Exagamglogene Autotemcel for Severe Sickle Cell Disease" to be shared on Monday, December 11 at 4:30 p.m. (presentation time 4:45 p.m.) PST.

This presentation will include important updates from CLIMB SCD-121, an ongoing, 24-month, phase 3 trial of exa-cel in patients age 12-35 with sickle cell disease.

Dr. Frangoul is also co-author on an oral presentation titled, "Exagamglogene Autotemcel for Transfusion-Dependent β-Thalassemia" to be shared on Monday, December 11 at 4:30 p.m. (presentation time 5:00 p.m.) PST.

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Chris Yasenchak, MD, Willamette Valley Cancer Institute and Research Center, Jason Melear, MD, Texas Oncology, John M. Burke, MD, Rocky Mountain Cancer Centers, Habte A. Yimer, MD, Texas Oncology, Mihir Raval, MD, New York Oncology Hematology, Miguel Islas-Ohlmayer, MD, St. Elizabeth Healthcare, Mitul Gandhi, MD, Virginia Cancer Specialists, and John Scott Renshaw, MD, Texas Oncology, are co-authors on the oral presentation, "Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine for Advanced Stage Classical Hodgkin Lymphoma: Efficacy and Safety Results from the Single Arm Phase 2 Study" presented on Sunday, December 10 at 4:30 p.m. (presentation time 4:45 p.m.) PST.

John M. Burke, MD, Rocky Mountain Cancer Centers, Mitul Gandhi, MD, Virginia Cancer Specialists, and Christopher A. Yasenchak, MD, Willamette Valley Cancer Institute and Research Center, will highlight "Brentuximab Vedotin, Nivolumab, Doxorubicin, and Dacarbazine (AN+AD) for Early-Stage Classical Hodgkin Lymphoma (SGN35-027 Part C)" through an oral presentation on Sunday, December 10 at 4:30 p.m. (presentation time 5:30 p.m.) PST.

These studies represent two arms of significant clinical trials exploring treatment advancements in classical Hodgkin Lymphoma (both advanced and early stage).

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Tonya Cox, BSN, Sarah Cannon Transplant & Cellular Therapy Network, is first author alongside seventeen SCRI/Sarah Cannon Transplant & Cellular Therapy Network co-authors on an oral presentation titled, "Standardization of Outpatient Care after CAR-T Therapy Across a Large Cell Therapy Network- Through Technology and Decentralized Virtual Nurses: Preliminary Results" which will be presented on Saturday, December 9 at 2:00 p.m. PST.

This study describes the innovative care model of using remote patient monitoring to provide chimeric antigen receptor T-cell therapies in the outpatient setting across a network of cell therapy centers.

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Jeffrey Matous, MD, Colorado Blood Cancer Institute, is first author on an oral presentation titled, "Talquetamab + Pomalidomide in Patients with Relapsed/Refractory Multiple Myeloma: Safety and Preliminary Efficacy Results from the Phase 1b MonumenTAL-2 Study" which will be shared on Monday, December 11 at 4:30 p.m. PST.

This presentation will offer an update out of a Phase I study for patients with relapsed/refractory multiple myeloma.

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Paul Shaughnessy, MD, Sarah Cannon Transplant & Cellular Therapy Program at Methodist Hospital, is a co-author on a late-breaking oral presentation, titled, "Reduced Intensity Haploidentical Bone Marrow Transplantation in Adults with Severe Sickle Cell Disease: BMT CTN 1507" which will be presented on Tuesday, December 12 at 9:00 a.m. PST.

This presentation presents the results of a Phase II multi-center single-arm prospective clinical trial of haploidentical transplantation in adults with severe sickle cell disease.

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A full list of presentations can be found here. Investigators highlighting research at this year’s ASH (Free ASH Whitepaper) Annual Meeting & Exposition represent studies being conducted across SCRI, Sarah Cannon Transplant & Cellular Therapy Network, and partners from The US Oncology Network and Ontada.

Seres Therapeutics Announces Presentation of Preliminary PK/PD and Safety Data for Investigational Microbiome Therapeutic SER-155 at ASH 2023

On December 7, 2023 Seres Therapeutics, Inc. (Nasdaq: MCRB), a leading microbiome therapeutics company, reported that preliminary clinical data from a currently enrolling Phase 1b study of SER-155 study in adult patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) will be presented at the 65th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting held from December 9-12, 2023, in San Diego, California, USA (Press release, Seres Therapeutics, DEC 7, 2023, View Source [SID1234638276]). SER-155 is an oral, cultivated live bacterial consortia investigational therapeutic designed to prevent enteric-derived infections and resulting blood stream infections, as well as reduce the incidence of graft-versus-host disease (GvHD) by modulating immune responses in the gastrointestinal tract.

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Poster Presentation Details:
Poster Title: Impact of Investigational Microbiome Therapeutic SER-155 on Pathogen Domination: Initial Results from a Phase 1b Study in Adults Undergoing Allogeneic Hematopoietic Cell Transplantation (HCT)
Poster number: 2198
Presenter: Jonathan Peled, MD, PhD, Memorial Sloan Kettering Cancer Center, New York, NY
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster I
Session Date/Time: Saturday, December 9, 2023: 5:30pm – 7:30pm EST
Location: San Diego Convention Center, Halls G-H

About SER-155
SER-155 is a consortium of bacterial strains selected using Seres’ reverse translation discovery and development platform technologies. SER-155 design incorporated microbiome biomarker data from human clinical data and preclinical data from human cell-based assays and in vivo disease models. SER-155 is intended to restructure the gastrointestinal microbiome by decreasing the abundance of bacterial pathogens that can harbor antibiotic resistance, and introducing bacteria that provide immunomodulatory metabolites that can improve mucosal barrier integrity and reduce local GI inflammation. These effects are hypothesized to reduce the likelihood of pathogen translocation and subsequent bloodstream infection and GvHD.

Aura Biosciences Announces First Patient Dosed in Global Phase 3 CoMpass Trial Evaluating the Safety and Efficacy of Belzupacap Sarotalocan (Bel-sar) for First-Line Treatment of Early-Stage Choroidal Melanoma

On December 7, 2023 Aura Biosciences Inc. (NASDAQ: AURA), a clinical-stage biotechnology company developing a novel class of virus-like drug conjugate (VDC) therapies for multiple oncology indications, reported the first patient has been dosed in the global Phase 3 CoMpass trial evaluating the safety and efficacy of bel-sar for the first-line treatment of adult patients with early-stage choroidal melanoma (Press release, Aura Biosciences, DEC 7, 2023, View Source [SID1234638275]).

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"Dosing of the first patient in this global Phase 3 trial is a major milestone for Aura, and for patients with early-stage choroidal melanoma, a life-threatening rare disease with no approved targeted therapies," said Elisabet de los Pinos, Ph.D., Chief Executive Officer of Aura. "With the SPA agreement from the FDA, and a strong endorsement from the ocular oncology community, we continue to move bel-sar closer to potentially being approved as a first-line vision preserving treatment for patients living with this disease."

The CoMpass trial is designed as a superiority trial comparing bel-sar versus a sham control. The trial is a global Phase 3, randomized, multi-center, masked study, intended to enroll approximately 100 patients randomized 2:1:2 to receive high dose regimen of bel-sar, low dose regimen of bel-sar with suprachoroidal (SC) administration or a sham control. Aura received written agreement from the U.S. Food and Drug Administration (FDA) under a Special Protocol Assessment (SPA) for the overall design of the CoMpass trial.